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·GENETICS FOR HEDICAL STUDENTS

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·GENETICS FOR
MEDICAL STUDENTS
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NA D.&., I.L.
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·PREPAC. TAL IMPORTANCI of Genetia b being Iddy recognized by tho Wedlal Profendina. Practitioners require a knowledge athy rubject to the coure of the work, and students are Duced with it in ezaminations. Yet thongh text-boob at Gepetlas ure anlable in great variety the member of them wbleh treat of human heredity to me. Indeed a work providing a bold and cementary introduction to that subject has long been required, and this book in an attempt to meet that Dcod. The scopo of this account has to omo atent been deter mided by tho apertence gained during many yours of teaching Ganetla to medical studenta at Orford I beve mado no attenpt to prezent a compendium of knowledro ao tho rubject. On the contrary the book is designed to illustrate to chle principien. Consequently the roas tnberfted conditions which are descobed have been chosen Mostrativo Instance only However I candiled Bst of Home of the more important, of well uthenticated, of tho robo kdown to Van provided on Pp. 140-01 Furtba Information on them abould be obtafood from morbus dovoted to spoolel branches of human Genetion. Among the one bo ruch outstanding merit that I wah to draw attention to it bert I do to E A Cocbonyos Inturied Abhorrektia of the SHR and its Appondant (Oxford Pram, 1993). The cumples which I bare employed are mainly human, bat I have made sparing o of other material where this keemned particularly ppropriate and helpful. Thus to decibo sutarcoal Inbyge without reference to lower forum would greatly ember the explanation of phonom od whilah has an important bearing on mediaal work I hope that those who read this book will not be content tood that peoctie studies with it. Inabre Bibbogrphy I bero pogrested for rob wblob apply more detale Information on the publects crored by ach chapter so that students may bo able to attend the knowledge to the 1

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·PIISAOB Pource de constant courgement and bop bo all brinebor of my work It irery important that . Hacindon a human Genction abould conform to the requirements of the medioul profontor, Da li to preole scope, lodged from that point of view cury to dcine. I have been partioularly fortunata, therefors in obtaining the advice of Protocr t Lo Crom Curt, F.RS, upon this matter Lodoed, it w at hla restlom that this book watten. It ha pleurure to record myyntitude to ble for the recorderable trouble whilah ho has taken in reading sod writtebing it. I obool aloo Iko to express my grateful thanks to Profcunor I 8. Goodrich, P.RS.. for his belp. Protemor G D Halo Carpenter has been wo kind u to read the proat, and his commeats bavo been of great ustance to me. Dr G L Taylor of the Galton Laboratory Serum Unit, how van mo the benefit of ha valuablo advice on thomo noction of this book which deal with blood proaping I am mott prateful for ble help. I am fodebted to the Balltor of themes of Eurico bor permission to pubbub Fix and Tablo P I should like to express my thanks to In L. Nicholson for the care which abo has taken in preparing High 1-8 It had been my intention to subwoft auch chapter of this book, u It wu itten, to my own, Wulum Howland Tirardam, HD, the well-known authority on tabaculod. The keen toterant which he tool in its plen wau un focutivo to write it is death during the couro of tho work has been prent low to me. The adrico al mo who was embent not only to the mattoel pratendea bat - Baury critto and artit el coeptional attainment, would have been of och rahe tn preparing the furoy of human Genction. EBF OUI, February 1993 ·PREPARE TO THB SECOND EDITION 1100ND EDITION of this book required to little moi then two youn doce its first publication, and in that ain tho subject has not adnunced suficiently to nocoosita! comedoublo alterationu creept tn regard to the Rh bloom group. The recent work in this field is of much importano doce it provides a bade for the treatment of anther como condition of tho Borbom. As scoounts of it are not y wilable in text boola, Vean, Methuen & Co hero kind Dowed mo to add a third Appendix (pego 182) in whloh bero rummarised the mbject. I havo, in addition, introduct low other recent recolte, und made . number of correction clowhere in the text. I um much todebted to Profemor I Monro Fox, F.RS for most kindly drawing my attenthe to two paragraphe which required adjustment, and Professor W E Lo Grou Cart, F.RS, for bbs Tuluablo bat ·CONTENTS PLO L PTE PACE ZATO L MUENDELLAN HEREDITY L Woodler To Lan 1. Labuo ad Crong ovor, m. Maltiple Abokomorpha L THE GENETICS OF .12 L sa-determostios. Sex-Hala poma) Total Sex-bobom the X-strutonomo(5) Partagen Molat) Total Sor-baby tn the Y-chrornoounc, IL Tb Set-atlo I LUTAMAAN THE NATURE OF LIDIT L Yutatlon. L. Tbo Naturo o Beredity 74 THE ACTION OF THE GENES The Bitect of the Goa , Dominence Hodik atlon TL Baytroomcnta Yotation Cenetlo Phry bolo to Van 00 V POLYMORPHISO 1. Introdoction L. The Tute Tut IL Tbe Hood-group) Tho O AB Saces) The KN Serior-() The RH Group N Pretion Appllontoos L NETTIODS OF STUDY IN HUMAN GENETICS 111 L Filomentary Quantitatir Hethode i Lokar in Mon, m The Detection at Ipholted Condition I Enganda

·GEXETICO TOL KEDICAL STUDLXTS
LOR
141
I
149
APPENDIX-L Cytology
Credo Lot of Bome Home Cenas
IL The Ith Group
BIBLIOGRAPHY
163
15
REFERENCRS
165
INDEX
180

·CHAPTER I JIENDELIAN HEREDITY L WINDELB TYTO LATI TIL FUXAX BODY with all its attributes, b. product of heredity and environment Netber of those two endas I coustant, and changes in then may lead to Yudathans in One or more phyucal or mental chanotert. In studying the Interaction of two variahla tt talny desirablo to consider each wpuntely before anamining thetr Jatnt effects. Therefore we will first discum the operation of tberitance, and abrequently melyre the part played by the environment and ita internetion with heredity (see Chapter I The character of the body in the widest sens, are con trolled by hereditary factors (orama) present in every cell. They aro purod from parent to offspring in the gunetan Theac renien ebat in patra, alled Jelomorpb wbomo TOETAbeti ere derived the one from the father and the other from the motha The two genes composing much allelomorphio pairs may ether bo dimilar (bomoaygoon") or die dodlar (heterotypour) and the individuelo porrenting rob allelomorpba are called bomozygotes and 'heterozyrotor rospectively The dmplest dtuation therefore that in which pren charcoter be determined by a pet of hereditary (motorn. Instead of coutaminating ach other when brought together into the name cell (blending inheritance Pp. 08-), the roos retain their Identity (purtleolatu labaitance, pp. 08-70) oven tbe unlike members of a pair of heterosyroo Thelomorphe remain quite distinct Fetilisation is an add tro process for the gametos uro dllectively only bella cell ech, and they combine to produce the 'Tygote which is tho fint cell of the nom organim Somo mechanlama mut there loro adet by which the member of ach allelomorphlo por of FDA are reparated from one anothe kod per into The Who Lo Looslednat Cytolog anded to row Append. I pp. 14-5) beton beplantog 1 book T ·8 GZMETICS TOL MEDICAL STUDEXTI dirfarent gametes. These then contain but one member of cach of the allelomorpha, the pun being restored & fertilization These conclusion on the naturo of heredity were fra mundiated by Father Gregor Mendel (1877–94), working a1 the Augustinian monastery of St. Thomu at Bmo (ther alled Brunn) in Honaylı, of which be lived to become Prilat Ho rummarized his retults in the form of two Lam The first of these may now be considered. Mada's Phra Le (TW Low of Saration) states that characters are controlled by pain of gene the memben a which parte, ar gata, from one another during the formation of the germ-cells and pe mto ditarent gametos The patrs are restored at fertition, which allows of the rooombination in definito proportions. Consequently the characten to which they give riso may also regregate: for tbcy-l appear in abacquent geocrations with definite numerial frequenter It will be apparent that thb Law Concoded with two met of oventh. The behaviour of the genes, and that of the chaructent to which they give rtec Segregation relate fundamentally to the reparation of the pairs of gede from Ono another and their perage into different gecoctes, but It was inferred from the valblo reparation, or regregation, of the chancters which those gede control. A Dating between two organbon -hieh differ from one another in respect of a pair o contruted chancten (p 18) prodace a boterozygous form wboxe penince, for our immedlaste purposeb immaterial. Meodd found that if two rooh beterosygoten uro croured, the odginal types will emerge from the hybuld mbiture u pure u they were before that they begregate to the mucceeding generibog, und in definute proportions Wben Mendel published his resulta n 1800, DO mechanism w krown which could effect the station of the roa. However hot rork wu long Ignored and only receved due attention in 1000 Irteen yan ate his death. By that thos the chromtorno bed been discovered, and it wu moon ·WBXDILIAN HOLIDITY 9 obylou that these constituto rehicles perfectly adapted to any tho pela aod to copure their weyropattoo. The parallel batudeed striking between the behaviour of the chromosome detected by the microscopio study of cell, and thet of the gene, determined by tracing the inheritance of the chancters which they control. The genes and present in patrs (alletomorpha) u are the chromosome (homologou chromoroma) The member of the pain, both of gma and al chromonra, are daired respectively from the two parente Conecquent upon Hendalian sareation, the reno com tating the allelomorpha reparate trom one another and pax into different gametos, u do the member of the homologous pain of chromosomes, Owing to metard Tbo gameton then contain 000 member only of the pun both of good and of chromosomes, but then aro restored by the additive naturo of fertilization. It will later becomo apparent that othe equally exact parallels cordat between chromotores and genes (for cuample, thoro provided by roadng-orer PP 140-0) Bat the churomodne theory of baredity is not dependeot upon mere dmlarity of behaviour howeve strange that the chorobonomo carry the reader in fact which has now been demonstrated by mmy teal arportinente It will at this stogo be bepal to take an cumple of the Working of Mende Art La Serenl other consequencom of the operation can theo adly be appreciated. For this purpom wou trace the Inheritance of peculiar condition of do direct, though a coordenblo Indirect importance (p. 108) In manlod, about one individual to four fa unablo to tasto the argando compound phcoyl-thbouren und som ofita chemlal Jaa la concentration so low us atty purta por millon" Thla rubatance u Intensely bitter to thon wo aan detect it, and he the fananla -NHC-NH, MI For any thject modt ud (11) O Weddlosto (1 Netto Ato detect Abomatration of 100 parte po blatokatla) ·10 OCXLTIOS JOB MEDICAL STUDENTI The ability to taste it » due to the action of pair ol gener, which may be denoted TT However they may not in another form (£) responsible for the inability to do no These two types are both homozygou, for the clomorpb with whloh we are concerned are made up of dmilar membert both T or both . They are carried respectively on puit of homologowo chromosome which separato from each other during meloda, ono momber pearing into each gameto. The brings about regregation, so that every gamote contain ooc member only of the genes determining the power to taste pbenyl thtoure. This taster produces gemetas cach containing • Anglo T while those of non-taster cach contain t only Shoulde tuter and a non-taster marry thefer children will possom pairs of bomologous chromosomas once mort, whose components are derived from the father and from the mother These will each carry • gene controlling this particular tasting faculty Thus tho patrs of alelomorpbe are restared, but there are boterorygous patri (T1), composed of T from one parent and t from the other (Fig 1). In como conditions to operaton of two unliko delo morphs give rise to an Intarudlate effect (p. 118) Mare otten, howeve tho heterozygotow dovely or completely rekublo ono of the homozygou types. In these circumstance, when tho samo result to produced in the heterozygoto u in one of tho homosygotes, the chancter is called . dominant The alternative character which is obucured the heterozygoto end appear only in the other homozygota alled receive The foability to taste phenyl-thio-ures frecendre, so that the heterosypota mantfort the dominant condition und ero taster Heterozygous individuals, produced by a mating of two homosygotes, ero rold to constituto the first Olial (or F1) generation of the family which is being investigated. The original parent than belong to the Art parental (Pi) merabon. When It to Docenary to refa to the mand perents of the Fi generation, there are denoted by PT Add ooo backward. A mating between two individuals of the Fi penention gives store to a 'second Allal (F3) generation ·KENDELIA HEIDITY 11 This cannot normally be studied directly in man, doce It arte from brother mod deter marriage. However its qurulat, for our present purposes, la constantly cocoontered Amirclego between two heterotygota. Tbo rerulto to which this gira dhe most be considered in some detail. A betarygoas turto area tho diamlar alielomorpha TL Careequent upon melods (Ke Appendix I), the guneta thoortrou) hemorygou Tel. The production of bottrodyroton from Typ between the two contrusted borrory oo typen The daroten on the ability to taste pealthlon who doent to the baby to do no roeire one memba only this pats of gues, Tort Sportas or cap carrying we typo or the other are thus produced in equality OD « marriere between two much heteroaypoten, the chances ut qu that apem cutyine T meets and aying Tarho producing spota of the constitution TT and Ti in equal number, Similarly with the equally nomerous spams carrying twboleh, meeting the two type or us before produco 11 und Tootes, abo in equal number. Three type dotlspring therefore arte, powerlo TT TL, and Inntio of 1:11. These are the proper to always produced from the nandam cowbloation of two type beving equally pamperou alternatire pharer they are ·19 GENETIC. TOL MEDICAL STUDENTS dot the prerogative of genetian. I w toa together two col I considerablo number of time, our thrumi dvo 35 poc both obren 50 per cent, one obvern and one reven a 10 per oent both reverse three group in a ratio of 1 11 ou to the genetho lostanoo. However m the cumplo hi we are studymg the three classes of tyrote constituting t F generation will not give rise to three distinct clamos individualr: tutan imperfect tasters, and don tasten, 1 u arady mentioned, the first two of those are combiex due to dominance. Consequently two clamer only appe tastori Lod Don-tasten, in .8 l retto, reprezenting. 1 1 nuto with the first two terms added together (Fig 1) In dbouning the P1 generation of this exemple no indika tion wu given whether the taster wu tho malo or the femu parcot, and nono b needed. Sevo for those instans expeclally related to the max-determination mechanian, bo dlsumed in Chapter II, the two rexes are cructly oqi in the contribution which they malo to tho beredity of th oftopring, and the remult I the same however the gener types or the character ero distributed in regard to sex - dom bo ovldent, morcover that dominanta cun bo two gectic types, homosygotes or beterosyrota, wh rcccdva aun be of wo type only for they must alway! bomozygous, Wolve just camined the rorult of a marriage betwe two beterotygotes. It la Do Docenuary to consider the high fmportant stubon in which one parent 1 heterozygo and tho other a homosyrote. For this purpose we will u the name chancta u before, the ability or inability to ta phenyl thło-ure as already to dlated, beterozygous taster been t1 roa Ty on a homologout pair of chromosomes, and the rpente during melodis, carrying T into one ball of t] gunetes and 1 into the other Howeve the poortaste beng receive an only be bomozygous, and poskee #1 that all the puneta while they form are dmilar and aty In a manuge favolving these two type it is traumatori which of them to the male and which the femal, and th ·ILXDELIAX FIIDITY chances are equal that the gameta of the non-testers, Decor wrly provided with meet guneta bearing T or t produced by the heterozygote. Thus when the patrs of bocoologom caumonoma, and consequently the allelomorphs, are so stored at fertiliation, the combinations Ti (testa) and # heterorygous TIt FD T т t Tit Iratorycous Ithomorto) Zhatworpus utas At PE. Superetio pong the bildet for between two betrunyata to bolo are the man Yy1 (non-tasta) tro produced to quality heterosyroto od bomosyrota appar un . natto of 1 L This snaple type of mating balle. back-crow because it trults when heterosyrote, of the F7 generation, is crowed back to 006 of the parental farmet but It must not be so dellbed, for It au atne In other niye Rather the following definition should be comployed. A back con su mating betneen. heterotyrote and a bomoa youts, and it lada to repregattoo Thli osprente all the mental feature of the to equality 1 ·14 OLXETICI TOL MEDICAL .TUDENTS dtuation. The Indrriduals produced by a back-cocoo stitute what I called an RS geration (F18 8). With an intermediate beterozygote, back crow to ether homozygoto will lead to the regregation of dathact charctent When dominance in complete, however the result to attained only by the back-crow to the recedure. That to the bomo Tyrou dominant produce an exparently uniform AS, heteroryous (homoryou Tt hoterarygous Tlt Thomcrypour) mnder DE LA back-cow (hetero potem bomo proto in that repution talon place to nato of 11 LONG the othples of this type of a The do are the met P 1 Kod resembling both parents, but condating of homozyrote and heterozygotes to equahty Tho reality of this segregation, Concouled - it ., coald bo tabllobed l the member of soch. Regum top were to mate with receive indholduul. Hall of them would then produce the dominant type only und hall would produce dombrants and recentes to quality The clamatest jtat Auggested by un important one. For we wble to determine the renetto constitution of an individual during cpaimental Tork on animals and plants, It always desirable to crow It with the recendre type. Tho od nature of thb borident, since rootedre ute of known wortitution, being necessarily homozygou, and allow the ·HEXDELIAN ILIEDITT 10 demonstrablo regration of rectora u Tell us dantranta Dory their odepuing when mated with beterozygote. A tart of this Hnd an, of cours, be eroployed to prove the truth of un resertion made at an arlier ses that the 8:1 nuto obtained in F2 regregation in reality ratio of 1:1:1 obecured by dominance. I coob krogatog dana nanta bo mated with recruites, ond third of them will produce dominants only the remaining to thirds - prodao domimnt and recendres in equality this be back com rorult, and it arise from matings between recenives and the concealed boteroxyrote Candy the document cu of the F generation be composito one, including homo Trota kod heterozygotas na ntio of 112, u postulated on theoretical groande. We have now considered the two types of regregation which and take place with singlo-factor inbertance that cbarcteristic of the F2 generation and of the buck-com Furthermore, wo bato seen that it ipodbilo to demonstrato tho Oocurrenco in both of them of the fundamental nutis expected, cven when those tro obecured by dominance It hm already been streamed that one of the most important properties of roch pregation is the reappenance of the original homozygous types ardong the offspring of hetero- Tyroton. When a marriago ocuri between two sumular Loudosypotes, both Dop-bastons of both bomosyon taxta to o amplo, all the progeny ure homorypotas also. Further the type ranaina puro indefinitely until a mating with tho beterosypote or ith the other bomo yoote tako place. That is to my homosyrow loo always breeds truc whotha thorones han pued through a beterozygoto ar not, and to reda do not coataminate one another oven when burvaght together tnto the sume cell. Thu Hendelan heredity be provided on they new concept of the hytod, do o modelo not of bknded type, and of the purity of tho hereditary units Both the ability wod tho inabolty to taste phenylthio-ura Aro very cocamon couch tons in the population Hometer the study of bereditary dhouse constitutas an important ·10 OZXETICS YOL YIDICAL ITUDEXTA upect of human repetics, and here one of the altapatint statas ll be nure Thu leach to certain Atuation wilch require boef mention Pradedea Aude narre disorder in which a depan tlon of tho nervous system produces et instalow of power In the lower extremities. The parlent may as be saade, and will with dualculty later tho atarda turolves the trunk, mes, and bead, speech beoorde dibuit, and advanced aures may be unable to act op Tbo condition to inberited dmple teocalve ud, consequently it can hardly ever rio cecept fromg mating between two heterorygota Since the dihase lipeally appear during the recond deerde af life, thon diected by It will certafnly reproduce loss frequently t an normal individual. Even so, all ther alopering I almost larunably be of the normal (dominant) type for only when they mery close relattre (pp. 181-5) is there any reasonable pouability of back-cron result, which would obow that the ostensibly healthy partner in the union 4 in reality a heterotyrote still let in it likely that . minage between two weeted pomus l over be observed. Tho it o clear that those wataing trom rire diense inherited u « dmplo reconfro will almost always havo normal parrots und, at int that the condition will appeur marelv spored cally in the bostory of attooted families. Special quaillation ore aboo Decorary in condering nunc copditoor Inbertted u dmplo domlounta An aficated dividual wh then have an attected parenta direct histog of the condition being traceable to one ancestral line in unbroken RCC doo (except for the rart occurrence of mutation, tee Chapter on. Consequently the gene concerned to perpetuted through a serker of beck-crouts, producing portal and elected heterosypu individuals la approximate equality to ach generation. Hating between two heterowyrota, ach therefore manifesting the no discu* lo question, are liable to be of immense murity They aro bort dy to otre from the manage of close relations and in thora conditions in which the hability does not appear until after the softwa ut of purtatbood. Huntington Choren ·NEXDILLAX HILLDITT 17 ku dmple dacunant of this Hod, though to far studied oly in the heavyrou phur, fæ the symptoca eldun becomo poticeable before the ye of thirty wod otten ktor It ta chandtatred by tnvoluntary musculo morenents, kod mental detadonation programing to fanfty It will be clear that the circumstances attending the thundon ou ruro dominant dirane hardly over permit its manifestation in the homosypou forn. Now the deind ton of doutnant condition bone to which the citcot of the beterozygoto bindtagalubable from that of one of tho bou.caypotes. Yet in the nut majority o' the art aberotan which have been deroribed us emplo doutoants in man, m opportunity has arisen for comparing them to the phone Het domine noc In reality means no more than that tho discer, or other characteristio ta question, wtfactorial and la emprened in the beterdaygotes. In other animals and plants, in which experimental studia are ually poble, mrcha Atration should not be deambed ua donnent until the betaroryrotar hare been coropared with both horno tyrotes and found to agree with ono of them. For tho occurrence of truo dominance to al much evolutionary dgni fence (Chapter IV) and should not be confumed with that In which the beteroayroo etteot la sperately detectable. Ia mun, however it may be extremely duiloult or tupovabilo to obtain the Information Decorary to draw thilas distinction, while the term domidence has been wo wldeły wpplied that it ought hardly bo practablo to attempt roverely to limit Ita unc. However it should alway be clearly indicated whether or not the nature of dominant chernoten bus been estabilahed. Indeed, it is highly probable that many of thoro that are alled in men and Dot, strictly speaking, docarpanta at 2 (pp. 85-6). The analyse oo far undertaken bes related to the screen Hon of Anglo patr of domorpbe upon the best of the Ant Law of Wendel 1 second best concerned with the behaviour of two a moro pobo of gene when stodied together ladd. Second L (TW Led Independed durin) ·18 QENITIOI TOL MEDICAL STUDENTI states. When to or more pen of genes segregato sinal taceanaly the distribution of any one of the independent of the distribution of the other That is to my if we conside two chanctont regrerating id 8.1 natto, this law tells us that nothing interferes with the random databation of ach there to do tadency for the parental combinatons to be prekrved in the otpring Dor for the two dominant and the two recentivo types to agregato together Rather the repult will be the mathemated combination of two 8:1 nthos that be to y . ratio of 8:8811 It is not known that Bendel's second law i abject to cuocptions (pp. 13-0). However its emplo operation must be discuued before these are conalderod, and this may be donc mort con rendently with the help of an anampla To will take for this purpose the character aloudy used for illustrating Mende'. Ant Lar the ability to taste phenyl thlo-ure, which is dominant to the inability to do ng, and consider its segregation in relation to that of another chur acter the posterior of bright red hair which is wailectoral und rocesure to non-red shades Actually the antenot a u mal amount of red plgment to the hair pometimes moclated with freckles, may represent the heterosyrous condition 1 w, much beterozypour opteazion a rather Verable and not a mys schloved, Dor it fully proved However the point in not one which need concern The full red hatred condition, being recentre, must bo homorygous, and b dute to the operation of a pair of gener which may be denoted it Tbs dotloant pag-red balred atate being represented u RR O P Attention abould be directed to the nomenclature. It la convention to employ the same letter for allelomorphic res, tuing the capital for that produdng domimat lects and the imall letter for that prododag roepe ona. The foltlal letter of one of the ctm selected when appropriate. By this means the dation between adelomorphs is apparent when symbole look are employed. The double bomorygora dormant (TTRM 6 - tester ·NEXDILUN HEILDITY 19 with non-red hair Men und woment of this kod poroduce gamete poeding wo member of ach alleomorphlo patr They must therefore be all like, currying both I add R. Similarly the double recuadro (tr) which s A don tartar with red hair produces gumota oopped with t and On a marriage between mich individuals (tho P1 generation) an F1 generation is produced which mut conet of Angle type double beterozygotes of the constitution Tier und ther, manllesting the two dominant stater, vil bo tusten with pon-red hair Consider a marriage to which the partoo kro order to this FI generation. Both.Il cory T and I respectively upon one pair of homologous chromosomes, and R andr upon another pats in cvery cell or the body During moonis the pulos of chromosome will reparato from one another into different fumetes at random, to the rent that there to do tendency for tho paternally and maternally catred material of ach pair the rootboas containing the spindle attachment, for emple, to puw foto tho megametos together Como quently the chances and equal that I becomar Inoloaded to puncte with Bar with t dmlarly for the equally mmametot ia. Thu four kinds of gametes, carrying TR TY IR, rod are formed to equal numben by cech individual Theke panetto typer an bo combined la tuteen poedblo wy, lustrated to Fig 4. But they give rimo only to four distoot cases, owing to dominance. It will be observed that oino al the recombinations contain at laut ono donlount member of both pato of allelomorpby, and are turter with pored bar threo pouca u cod at least one R and are non-tarters with non-red hair three power and at laut oder being testen und red hatred, while one 11 of the doublo recadre type thet a Doo-taster with red befr There four groapa urte la a natio 0:31811 whilch represents ther frequency in fachgerentia Only one true breeding member of auch of the four dames - Is Incoded in a famly a tha kod (TTRR, ARR, TT, and #t). Consequently the proportion of bomozygota booomnes progradrely low to the larger of them. Ao Inspection of ·10 GENTIC. TOR MEDICAL STUDENTE F1 Rondlet TR Tr tR tr TR TTRR TTRI TUPR TtR tester toster taster non red her non-red hat nonned her non-redhak Tr TTRE toster nord har TORT tastor non hair Ttrr tacto red haar red her F1 TERR tato tR TtRr taster nadhar tt RR ttrr nontale non-tater non red her nondhar monedha tr TtRr tanter monedhe Ttri tortor redhur tt Rr non toga monedhar itir non-tatur red hair F. Beration among the afterpang of two double heterozygoto The churroco are the ability to in pbeyt ihto-ure, dondoeat to the habity to do mund the poemton noored hat which is dombant to the rod-fetred coodition. Each leterosyrote muutosta the two domto cot types od ourdes Tundt bo ooo bomo logo patrol MoOW w Rod to another Theythorsten produce tour dead pametan la eqohty Theann be combloed to 16 pouble mur protong perto composed otten with poo-rod hat I to with red bar & Doo-tado tu noored Lal and imo-lator with red Fig 4 ale abom the fart omgregation which would have taken place to the absence of dominance. All the genetically obtinct dames would then have been apenble. That are pire of them, wyregating me nato o 1 1:2 1:4 2 1:1:1. Thoy TTAR, TTT TRR, ITA & R THT ORR, HIT ·KIXDILIAN HEILDITI It is important to examine the dtuation arting from * back-cron farolving two independently worting Jelomorpha. Yo here seen that the double beterosyrote (TUR) being • taster with nod-red her must produce four type o punetes (TRTUR, t) to equal numbers (p. 10) ALO that the non-busto Ith red her who are double recendva (tort), an produce one type only (tl. Clearly marriage between two ruch individuals munt yield all four danes of otirpring uten with non-red hair and with red har Dootaster with non-red od with red hair Since thu . back-cron, constituting en Regeneration, there will regrorate in equality (pp. 18-14). The result ilustrated in the lowest bortrontal HoooL w.haro Dor analysed the working of Mendel second lew to both of the fundamental penetic dtuation thomo provided by the pancration and the back-crom. For this purpoto mod the implant toutance, that to which two purs of Delomorpbs only ure regregatio However the mecood law bodianto the nation to be aspected when three or bigbar rrumbe al allelomorphs are involved. Thus the trt-hybrid' ratlo, that arising from a union in which both perents are beteroryrons for three part of allekamorpha, leads, with dominance, to the combination of threo I I ration Independently that is to rey to a ratio of 57 OO .:8:8:1. There are now trenty teren ponetically datinct cuman bod, without dominador, each of these would produco . hopente cilet. A mating between the triple betootypote, manllating all thrco dominant charcters, and tho triplo recendre will yield eight clues Thema will appear in quality for this to back-ero in respect of all three factor In concladon, it must be noticed that the operation of Mendel's roomd bo prorides an opportunity for good which bere ai perately to be brought together the la obviously of meat value, dince it alon adriatagcom checten powered by different sector of nice to be coinbloed in the mume hrdual ·GEXZTICS TOR XIDIOAL STUDENTI L. LINKOL AND CROSSTKG-OTER As already plained, it is now establlahed that the fena are carried to the chromosomes (p. 0). Thus fact reta a Kmit to the operation of truly Independent assort ment, mo that Mendel's second Lew not invariably *pplicable. The number of alelomorpha ponesued by the human peda h of como unknown General considerations, depending on the poolblo ure of the molecules constituting the genah, muggest that the total must amount to many thomande. There are twenty four pain of chromosomes in man, wo ft 5 obvious that ach of them mot carry a largo number of gede. There annot amort Independently M Mendel thought they did, once they tnvd in the same vehicle and consequently may be expected to reach the amo destination. There is, of courr, Do berria to the independent mwortment of Telomorphe carried in diferent part of chromosome, and this b tho situation which we have to fer analyzed. It á indeed that generally to be antidpated in the study of low sets of adelomorphs only for the human chromnomamen do not dilla considerably from ono another in are, to that the chances are not likely to be much greater than 1 in 84 that any two pain of allelomorphs are carried together in ono of them. Ezocptions to Mendel's woond Law of the kind fut indicated, constituto Intego This should be defined in the foJowing tour Linkager in the tendency for two of more pain of allelomorpha to stort together instead of obeying Vendol , eopod law of Independent exortment, beomure they are curried In tho umo pair of chromosomes. It will be convenlent at the outset to Ilustrate linkgo by means of a purely hypothetical erimple. Consider tro beterotypu alelomorpba da und Bb which are curled to the matte pair of chromoromes. We will first papporo that A und B lle together in one bomooloqoos pair of chromowana Rod a od 6 in the other consequently the genetlo constitu tion of such a hybrid individuat may be represented ·WINDCLIAN ACLIDITY 2 AB pad, 1 It may be regarded as the F1 generation of com whore parents, of the Pi generation, we shall stody rubroquently At made the bomologous chromosome patos mpente, artying AB/ together into one half of the pameta and ab/ together into the other half. Now doublo receYO hdviduals (ab/a) aun piro dia to one kind of gamete only bearing abl on methng between these two types, back ctor generation produced concuting of two dames only 4B(ab und ab fostead of the four slund wilch rhonid too with Independent wortment (compare the crumplo of this on p. 10). Suppowe tho gena had been differently arranged to tho doublo betenoaypote, A and I being carried or certo chromo- Foto and a und Ban the other to give the constitution A/B Od mating with tho double rcoordro (abjad, which produces / garasta mly two dawns instead of tho aspected Doar 10 gain prive; but this time tboy aro 1b/ab eod Thon laots require buried canddaution. In the Orrt lustunes, the genes A and B were carried togetha in 000 chromosome of the double betovayroto and a und wero oorled ba the other that has to pay the two doudoants were Inked in one chromosome and the two recentras to the On cronding with the double rrecades, that Am mochetoa b porod, fot only the double doentrant and double recendvo typo appear In the second boutadoc, one dominant and one recadro wort ausled together in orch homologous chromosome. This condition wu prevodno to the prettg back-eron fumilly which contains two conto o individuals only poroning 000 donant and an. rocontro churacta ach Tbo dtution presented by the Ant cumpte, in vhled the double domlounts and double recendre renain torether balled Comply That in whlab Goethe theoreom will be in torther ed Loy the 18 to not the couche bomo por parte the power tudo des hty the bank We boda bodo prep nl punts the comerparthed report the the ID Tot and he winter to the L A Power ·GLXBTICS TOL XCDICAL ITUDIXTI one dominant character does not appear in the samo fadvdual u tho other so that dominanta und recorded med to be repelled from one mother is alled Repulsion Itt reprezented by the second instance, Yet the parents of the coupling and of the ropuldoo pbar were canctly the rumo to appearance. The double recente wu of Identical constitution to each, and may therefore be dloegarded. The doublo heterozygotes would manifest the two dominant conditions in both acamples, though the dir tubation of the gena w different in them. Their homo Logous chromosomes contained A und B aud in coupling but 4 sod bs and B to repulder. This is due to the Aact that there double heterosygoo F1 individuale had parents al dostuct type. Thomo ero the grandparents of the anal back CIO generation, and may be dongnated P1. It be wplent to condder the station in which ach grand parental forms are bomozygot. In the coupling pha, they would bo AD/AB and ablab respectively In repokoontboy would be Ab Ab and aBlaB That lo to say they uro vidhiy dainot add, since we como dominance, thoy aro respectively a tho ramo two clases marire among their grandchildren. It is clear therefore, that in order to study linkago fully It lo decemary to powca Information on three gonerntion. For the parents af back-crow regregating for coupling or for repulsion between a given pair of allelomorpho Ill apport the mume. It is only when we carmine their grandparents (PI) to tho doublo heterozygous lino that we ato find. dutinction between thom. Linkego therefore involves Do umodation between particular gene u ruch, there is no tendency for comple, for dominants or receive to regate with one another Those gta which go into cua together teod to come out of it together I they are arded to tho same patto chromosome The theoretical cumples of Imkuge so far conridered art momowhat idealized, and they sto tostence of total linkage which, though known in the male of the trudt Ay Drosophila for lostance) is very mcommon. They do, horcrer illo trato in a particularly emplo my the manda in which the ·YEIDELU HLADITY chromontoo cataclan can limit the operation of Venda: second law Yet the facts of cytology will meet that Enkego co rely be completo Tbe intercben o sections al mataht between chronnat de derred from bomologous drummoner, duding the prophero of the first morot, must arty block of gena with them. Such a thndereDoc, bengan interchange of material without un interchange of perten, ☆s denonstrated cytologically by a chlume Genetically it produca croaring over in which a aro transferred trora me hotpologous chromosome to the other for the prophane chromatice (p-141) become the daughter chromosome of thowcoood melote telophare. Consequently Inked genas sro not Inorocably wodated together but can be combined in fronhy, wan thowo curied in different chromomo me-patos. Croning oor my bo defined as an interchange of linked fona conrequent upon a reciprocal trundarence of blocks of material between chromatida dored from boonologo chromosome It will be elftant to study coadingoror with the help of an aumple, and then to consider the general polnopilen which it forores. Unfortunately very little to yet known of this troportant phenomenon in man, accept to relation to the ma-determinadon mecbunborn (to be a plated in Cup to m Thadore it will be convenirat Ort to crutoo ito operation in another rafmal, and then briefly to discus larman bostanco o crossing over In nbittore y produces an enzyme whteh cables the animal to orldte my anthophyll whiloh It aab. The recontro condition n preread the formation of this entryroc, to that the fat becomes row in animal oopplied with frten food If this not provided in the diet the two condition annot be distingutsbed. Furthermors, albino receive to portal coloration, and is due to the operation of pair o goes . These are curred in the mme pair of chorocosoma u thon detonning yelow fat The day be detected blog by apply ad buth oth broth whooldatuto epout the ada ·20 GEXLTICS TOL MEDICAL STUDENTI A bomosypou normal rabbit (CYCY) Ill produce guneta artymg (Y/ while an abano with yellow fat (ly) will prodoce gumetas carrying al I these animal, which coneitate the Pi gencation, be mated, all tho F1 odlapatog will be normal to type bet double heterosyrotes of the constatation CY/ They will form gumeten in whilab the two Unked genes genendly remain together giving the types CY/ and y/ in equality However croang-ora occurs between there approximately 14 times in 100 mo that 1.1 per cent of the gameta become area of Cy/ while 7% per century oY/ If such Fl animal bo meted with albidos with yellow fat, being the double reseatro type cylcy which producer / gamotes only a back-crow generation is ob talnel. This fi compowd of 188 per cent of normal atroping (CY/yh and 41 8 per cent of albinos with yellow fat (cy/a) Thus the two grand parental typer have rappeared to equality However 71 per cent of these back-croantoals ore Dorically coloured, but with yollow fat (Cylcy) and 78 per cent are albinos with white fut (cYle) Thero to group, which reprezenta trendlerener of the Pi character, are called the recombination conta Together they meurt tho percentage-frequency of crosting-ove Thla tauled the 270#-OUT CIU (COV), and be obtained by adding together the two recombination desses and praying them. percentage of the total number of offsprmg Lo thla tostane the COVIH per cunt. Tbo cumpto fost demerſbed is one of Coupling Repaldon could have beco demonstrated by bring homosyrow foly coloured animals with yellow fat (Cy/Cy) od bomosyp wbudou wtb wbito lat (08/09) for the properation An Fi generatio of normal, but doublo beterosypouk, nabbit would have been formed before. If the were mated to double rooCAITCL, albłnos with yellow fat (alm), . buck TO would be produced. The would woodet, once more, of the two grandparental types in equallty each compriding Approximately 128 per cent of the otpring (fully coloured animab with yellow lat (Cy) od wbloos rith white lat, oY/C), and the two recombinatia deste (Donnaks, CTKM ·NIXDILIAX HELIDITY adatbtoon vith fellow fet cylg) also in equality compridng 74 pe cont of the oluping ach The faropolson, with. deficit of the double doutnanta and doublo recetare. The En groups appear as in the previous example, but then trequendas aro rovered. However these remain approti mutely us they are to rules, and the mount of croaring over kami maared us 14+ per cent by adding together the two recombination danas, though thek vo not the memo u balora Once moro we see that there I Do Location between the alleomorphe otept that of the poolboa ao the chromosoma All the gene unted on a particular chromosomo aro of coturk linked with one another It should therefore bo potable to go the Inked genes or any organen to le of proape if the chromosoma theory of heraclity to nid the number of such Hakept groaps bould equal the pumber of patro o homologoun chromosom. In the species The propoutoa hu been proved correct in all foutance in which the genetics are moontly known to permit of torting I Furthermore, when the pain of bomologoas chromosome diliter from one another conudderably to length, tho duo of the binkage groupe rura mooglily in proportion an toportant relationship ant between tho comover valume of three or more likod gepea If we consider three Anked gone A, B, und the crossover value between A und C equal ether the nom of the crorroger ralose between AB and BC, the direrence between them. This condition as only be mtided by logar relatiopship, and it demon Krute that the genes aro wie in line wala aloog the circumosomon Horwore it on the courtot onder o the gends to be ukertained. Suppono the cronovo ruhom between A and Bb, od that between Band C 41 Then the croworo natud between A und C vill be other for a If it be the rum (5), then the correct order of the sona b ADC: if the diference (), the correct order bARD The Dara together way to poses to on a chromosome, the wallet to the chance that a break and laterabeng of material will occur betmete them. Thereas the TOROTT ·GENETICI TOR MEDICAL STUDENTS naloe provide a relativo maupure of distano. In ou last instance, geac B les four uma u fer from A ut doce from C This last proportion will be strictly true for short distance only my under 8 per cent, for with a condiderablo length of chromosomo the possibility of multiple crosung-over annet When croesing-ovet oocun twice between two genes, the Interchango prodaced by ono restored by the other Thus the resulting doublo come-ova tadinduals aro wored in the non-cromover doma, so that the cross-over vuluo tuned too low but toplo croadng-over nulace it, and so on. How over the effect of multiple crowing-over be Dot po considerable u might be unticipated, doce the occurredoo of one crow-OTOT loterian with that of wother in its netghbourbood for Todog-over da determined in the cromosoma, and Inter twining threads have a model length of twist. Thou, far bort distances, the crossover nalue Dot obucured by multiple coming-over Tho tendenoy for one couver to provent the couTuDCO af mother in its neighbourhood is called Interfamos. It mcurred by Coincidence This calculated u the actual amount of double crossing ora between any gener, divided by the amount cipected. The expectation b the emplo probability that two CTOG-oven abould occur amultancoudy Thus, with a cover value of +0 per cent (obtained by adding together short lengtba), the expectation, in the abomed.co of interlermo, b that tho parent coeover value abould be about 16-0 per cent Owing to interfercooo it to found that tbc obrerved crossover vulgo relis short of par cont. to a los arteat than thai, It will now be ovident that chronoromo maps can be constructed from the date rupplied by coudng-oro For the rena can be egned to groups representing thome Stuated on the ame chromosome, whilo within those they can be placed in the correct order and at their relatie distances apart. A map a part of human chromosome obtained in the wy bgtven on p. 51. Apart from tho Linked ponos uociated with me, to be ·SO CIKCTICE TOR WEDICAL BTUDENTI attention bridly to their chiel chensterstiosund for that purpote animal material will be more convenient than human at this stage Voltiplo allelomorphs wally control gren met of charactent quantitatively so that they can be arranged in I senza representing the degree to which thereflecte depart trom the normal. In web • krles, the normal conditions wully dominant to the other, but when two of the mutant goues are brought togethe they product an intermediato roault (pp. 81-8). It will be realed that gena at the memo loow are represented by the same letter wong the capital for that giving me to the docolpant character Tho fact that I Knot of pena ou at the tamo loow to indicated by giving to samo letter to all of them and datingubbing the manbers by a buff. Tho normal alle lomorph is repre- Kuted by the capital without a hare all letton, the cod terom represented without a ruffle Shou pormal bo Inchidod, they ure indk RM. Thus the amount of black 7 the bar mouk b controlled by multiplo aliclomorphos. A (rebon belly) & (tho normal uniform a « (black) Had the effect of the to that of the normal (4), and darainent to it When animala pomcastag Cd, tho odquing and the the tries are not at the ame? dominant allelomorph of the other even if tho oflect of the goes wro For comple, the recentre pink-eye pig producen lo addition to the roduction in all the pigments of the dwo to pair of genes pp. R Allar ellects cxcept that the in more particulady s reducirca in tl Tong these two types (ppcher T ·NEXDELIAI TELEDITY 01 have the constitution PpCar There aro ardinary brown darl-eyed guinea piga On the other hand, the recendo white guma pig with red cya (strictly called the Himalayan type) y due to the operation of the gma cha which aro moltiplo adelomorpha od Cound or two other Conne quently og mating red-eyed dilute animal (de) and a Himalayan (ok), the normal condition b not restored among the otpring Ince, beng Jelomorphs, one gore does not bong to the dominant Delomorph of the other The P1 coartitution is dod and rich fodrvldoals are tater pedeste between the two parental type The result by dlagnostic of the behaviour of multiplo Telomorphs. It will further be crident that all the members of much worla havo tbe mmo Tomoret value with the other genes in thor chromomama Wo have now arveyod somo of tho cuentials of Vendalian ibertadoo thosently for the purpose of this book The tundamental detination between the add all other type of heredity which have been postulated from time to tune will be considerod in Chapter IIL ·CHAPTER I TIIE GENETICS OF SEX L III DIDERATION ILI 18 A quality which is inhelted, and in a dmple may For the two contruted character involved, melerau and femalencar, with all their attributes, regregato sharply from one another in proportions which, in the adult (PP 33-8) aro nedy aquel. How comploto thu segregation may bo ka matter of some disputo (pp. 80-8), but individuals obviously Intermediato to structure between the two more, though known, are of grout rurity Tho mechanium which operuta this ryutem muut briefly be conddered. Tbo genas controlling om Aro carried in a special pair of chromosomes called mar-chromosomes The remaining chromosomes, collectively know u autosoma LIO Dot directly concerned to actual sex-determinaton (pp 84-5) L. women, tho tro ka-chromosomas aro nimilar to no another and they do not differ coogderably from the autonomo, Icept that they bear, cumong others, the genes determining IL Tboy ero called 'X-chromomode Ven, on the other hand, powes an unlike patr of ke-chromosome. One of there is an X-chroidomomo datrod from tho mother while the other rocetved from tho father be atypical chromo no carrying few gera, and bono of them controlling wat This u the 'Y-chronoLOMO Thou in the human spearh with a total of 48 chromosome (24 pairs), there are 40 autoromas (20 poin) and one pate of scu-chromosome, contrating of two X-chromosoma in romca and one X und 000 Y chromosomo in men. During metods, the chromosomo number ta halved in poch any that ach gameto Iecara ono membe orary chromosome-pair Conacquently in addition to the compl? mento autonomes, althout receive a sloglo X-chrome Botte, whilo hall tho spermas receive an und hall recent * Y-chromoso. Thus the chance should be equal that

·TIL OLXETICI OT ILI
Roy Decomartly currying one X-chromosome, pa fertilized
by . I bearing pem, to productag malo (XY), or by an
X-barlog sperm, producing femak (XX) (see Ft 8).
Studies ou unloals ponending abnormal chromonomo
munben bere demonstrated that the X-chromosome are
XY
XX
х
XX
XY
TE A The ne du trividual datamed by the
Amb of X-chroom att om prodam
meln und to proteinele should caur the
production of the two balty to the out
tom Mate that the mostro matatan
be the X-chrome en marbrod between the
In octomtoo
the actual penta deciding which I shall dovelop. They
bare shown aloo that the Y-chaomovono ba generally without
Amidoudce to ro-determination, to to certaha proape tho
Amphibie, toe sample. In some forms the Y-chromonome
Habeent, so that the clorocosomo number to odd ba o tom
and even in the other Bot bort, u DDOTT wol,
Y-chromosome adath, Its lour, owing to waboormal cell
drdon, doot dot clect the development of the which
should pour it

·84 GENETICS TOR MEDICAL STUDENTI It is worth while to reflect breity upon there facta Wo have reen that the control of ki depends upon the dutaba tion of the chromosomes. Yet it will be observed that Individual X-chromosomes are not reatncted to any one rol. The angle chromosome of a man, respondblo for blancs u den ved from his mother where it wu one of the agents concerned in maldng her a female, hilo women must necennily posso tro X-chromosoma, one of which ako reaciva fron ber tather in boon it had been melo-deter mining (Fig :). That u to ky tho X-chromosomes ara constantly shuffled crow from ono ser to the other Claarty they cannot be differentiated respectively u malo or femaloproducing structures. On the contrary thar effect depende upon thar number tho ki determming mechanlam quantitative, not qualitativo, in Its actoa It is remarkablo that the kes poening the Anglo X chromosome is not the same in all group. For crampk In mammals It is the melo whilo in birda it is the female. Thu distinguishing Dames are necesary for tho XY and X type. The former la called the beterogemetio rer and the latter tho borogameto KI In human (and probably in all mammalian) geuctos heterogametio ser und malo are equivalent terme, but this is not universally true lo other animal. In man, therefore, it is the lather not the mother, whomo gametas determine tho x ol bus children. Numerot geba ato respondblo for a determination in the Mamah Tbore carded in the X-chromosomes are femalo determining while other, in the autonomes, aro malo determining The dosege of the former is therefore variable (In one or two X chromosomea), but that of the latter Aired. The balance between these keto is no adjusted that tho make-determinants, produced by the 11-genes in the auto ona, ure in effective com over the lamalo deter mining mubstances, produced by tho KI-genes to opo Achromosome but they are effectavely desdent compared with doublo that quantity of the femalo determining to dos to the presence of two chromosoga. It will be oppurent, therdory that though the car carred in the ·TIL GCNETICS OT ILI X-chromosoma uct u tho deciding dementa in modder mbaton (p. 33), obe equally respondhle for tho dadopt ore are curred in the wtonoma Tho ombryological and phyxoloqol uspect of ex must Dow be related to the chromosomo mechanim just decabed. The early embryo is capable of development either us a male Oru a female, having . complete outfit of the rudiments required to build up 000 or the other type of structure An aceu of make-determining rena, owing to the presenco of but I doglo . chromosome, and the degeneration a the cortical, or oturan, region of tbe guned, and the develop ment of its medullary or testicular cement. The secretion of the male bormona from the futensttual cells the testb eburn the growth of the male secondary scual character vu delcreps penk, und nocuted clande. It also caus tho retention of meronephric material mach as tho plaldym which barned backwards with the docending tosten Tho uume hormonas being about the degeneration of tho Mulledan ducts and other proncpbrte structures. On the other hand, the act of female-determomg genes, due to the procer of two X-chromosoma, bring about the revert met on changes owing to the formattoa od ovides and the scenetton of tho fernale hormona from their mtantial cell. Thu the accury w characten of both sexes aro under bommonlo control, being copecully stimulated to develop at the time of pubaty In Man, therefore, the chromosomno outft detamine the type of good which ahal develop, but only indirectly the condary and secury manual characters through the into mediacy of the bormoon from the tortes or the one. Yet thle artangtudent baby no means utreul, for to many forts, the forects for cumpk, Jomal character to directly determined by tho sa-gesa In mich animals at tration has no eicct bogood sterilizatiom, where the change of puberty cannot tako place in Man if austation has born performed carty in Hfc. Thw the voice of an ucha rematos higb-pitched and infantile Thero foot have an important bandng upon the production ·80 EXTTICI YOL MEDICAL STUDENTI of hermaphrodita, e tem which is commonly used to m iny mixture of the two keras, of whatever Hnd. In th animals in which the gonado produce do bormona, and k-chercters are under the direct control of the gene, abnormal mitodo muy greatly affect the ver of the individi For this may lead to the loss of an X-chromosome in hornogamotio , ar to the inclusion of two X-chromosol in a call of the hoterogametlo ki owing to the failure of daughter on-chromosome to reparato ut apbase. If 1 takes place in an early oel-dinoon, the prodocts of boornal cell may constitate up to me hill of the bo which is then of the oppodte ki to that determined fertilization. In this way melo end lamelo reglana dovelop ade by side. Individuals in which this occurs called tynandromorphs They seem to be posible o with localed re-control and cannot accur in Man, wb tho Ko the parts is not a function of the cells campos them but u under the central control of the good bormon In insccti, furthermore, the action of the wi-genes D become quantitatively different in various geographi Mcd. Within ach noe the necesary relationabup prekrved that one of two X chromosome respectiv caTy an effective deficiency or cicon of -genen. HOWC when race pocketing different absoluto Talue of the gena uro crowed, tho excen of the malo or femalo. determinants may be foolicient, ro producing anot type of bamaphrodito alled an interes Thu Individual which develops at first wholly the e PP priate to its richromonomo content, und aubecque mtcha over and develops wholly u the oppodto sol. I malo and female parti never form smultancoily: cud morpha and interna aro ka integradas in pace and time, respectively (for detailed account, aco Goldachmi 1953 In interment of a light degree, tho character of! inappropriate na uro thoso lost to be developed, whilo ar formal structures becomo progressively involved in moro extremo typa. It is clear therefore that the ge ·TAI OCULTICI OT SII control dierentially not only the quantity but the rate of production of tho re-detamining pubstanca. It probable, but not certen, that this Hnd of inter multy occur in mammal Races which have oralved lodependently may acquire different absolute value of their a. Croud between them might therefore led to un proficient excom o ono type ora the other and, conrequently to un incomplete mapprendon of the trappropriato portion of the originally ambivalent gonad. Subrotuant hormone production might then bo lected, so giving roo to con interpedlate. But the human races do not ppcar to have diferentiatod mufficiently from one another beforo Aubecquent interconding to acquire roch different abwoluto values of the kife. Another type of internat certainly known In momo mammal. This is the freemartin of oattles an individual of fntermediate res, which appean only as tho twin of a Dorinal make. In cattle twing, the embryono membrana grow together and the blood-vesela nastomouc, allowing tho blood and bOTTOODOS from one embryo to circulate through the other When the individuals are derived from «punto cup (d 1 gotto twins they may be al different are Tho touthealar bormons, which is produced before the ovenan, then creulates through the female embryo, preventing the further development of the otury nod partially converting the wondery and accessory renul character to the malo type No Auch phenommon u kdown in Van It lo by no means dear to what tho buman physoul abentiods of pox are duc. Yet it to important to notice that though tbe rougena decide whether the goods shall develop w tata or us ovaries, many other para deter moo the amount of hormone produced and it iming u well u the response of the theates to tt Such geret, es well u thoso directly concerned in ma-determinathon, aur, of course, mutato to other wholomorpha, which will allow of regregation in the wind way some I the combination to produced may cauo veak or shoonmal response atha to the make or to the female bormonas, piring w to instincta ·QLXETICS TOL VIDICAL GTUDENTS inappropriate to the phydaal won, perhaps combined of some slight tendency to approach the oppodto ant proportions of the body or in the quality of the robce. So aro romo at least of the bomore nuk though the purch logical attributes of that condition in Tay Bahlo leo bo environmentally produced, but doubtle moro cui in como constitutions than in othen. It is important alo 1 notice that tho development of the toll komal estivities reached gradually whilo peso cut which oontrol the ni of process in the body and the time of their onset (PP. 00-T indeed the facts of inter-foruahty demoostrato that th action of tho ki gena in sometimo (and perhaps alman atbly type. It is not upang therdore to fod that I phone of homonal tratinct he common in the adolesceno even of sexually normal mulas and females. The length a time that much tratincta perrig varles, no doubt bout genetically uod environmentally They may bo prolonged Into adult lưe, rometimen permanently but at other they pro replaced ultimately by normal pomal reactions Grous abnormalities in the structuro at the botual argent regresting intermedisoy un atremely rure to the human pocies, and they appear almost always to be in the direbon of an apparent feministron o malom But it should be noticed that the embryonic condition of tho atemal genitalia for more Io that of the actult female than of the adalt moale. A mero retardation In male development may there fore give the impremoon of any proach towards the female type. Such an eloct will wally be genetic, and the repling ahmormality to embryonio rather than bermepbrodite to probabie, bonete that true totul intaincettato art occudonally produced. IL ILI LOTAQL In the human species, the re-chromosoma contan punt more gma than those concerned with determination Thero nflect the widest range of characten und bear. Do relation to cos, except that beng carried lotbomme rebiete with the sites they are destritate relattro to throw ·TER DEIITICI of III 89 Whereu a not related to the karagation of the ordinary Litoko on which have been considered to the proclaw chapter It has been aplomed (pp. 12-6) that genes caur hod in the mide chromosome are add to be linked bean they export together Consequcotly thoro in the ex chromosome are allorar-linked genes' od they give the to ka-linked characters, owing to the sociabon with ser. 3 bd Y х b C T. The humus -curum The w I-abrood the BODY-chromoso.wb pomroction () compared a homologou cal o addoo thon kloog metion of the cromo (bs) whole Det homologoo hmatud Y And short motion of the Y-kromosom (1) Lata pot homologour with material to X The human X and Y-chromomonas are represented de grammatically in Fig a Tbo grotter part of the X-chromo roms from b to c in the figure, is not bomologoue with Y # that do croadog over and consequent interchange of material, an occur in this region. However one short rection of Xi homologous with the greater part of the much Fuller Y-chromovono (a to b in the dguro), while . very short length of Y (tromoto ) is not homologous with any mataia in X. Thus three types of linkago pocur in mun, doe to pone aandet (1) in the noo-homologou region of (to ) (?) in the homologous regions of land Y ( to a) ud (8) in the doo-bomologous region of Y (1 to ) Thero must be comddard In wmo datal. (6) Tool Setiap iw I chromosome Genes curred in the section of the chromosomo which I Dot bomologous with Y no respondble for total sahnbauge to tho x ·10 OLXYTICS TOR MEDICAL UTUDENTS chromow Thy is the most wel type and I tho 000 away intended when ka-linkage is mentioned, Icept vba stated to the contrary A notable cumplo of took a we linked charucter la provided by haemophille This is disorder in whlch the blood fails to dot. The phynology of the condition is by Do man clear It may be due to defeat in tho actintion of proto thrombio, but at may rato it does not appear to be tocated with any structura aboormality in the capillana (p) The patients bleed profusely from cuts, though their bleeding Hmo ba pennal doco the plateleto uro muffected. Cook quently oven minar opentions much us tooth castrabon art modated with much danger Slight blows may giro Hoto Tero broldag uod extensive bacmorrhagen under tho uldn. In addition, effurlons of blood Into the jointa may gradually produce stitch and constant pain, to deuden which becinophillea romotima becamo drag-uddicts. Such men ually die before the age of reproduction, but some may livo to the Age of twenty or twenty-five and prodoco children. The condition has attained considerablo notonety anco it be ntbe widespread in the royal familla of Europe. Hacinophile to due to the operation of a recondivo HI Inked gac. A woman, beterozygous for it to therdoro maffected, once she carbon the heerophilia pedo () One X-chrumorome, and its normal allelomorph (U) in the other Consequent upon mdoris, hall tho co what she producer will contain it and hell I only she wl usually Detypoxmal man, who has 8 lo hu only a chromosomo and produces to equal number X-besuing and Y-bearing operine Prom ruch union Love types of oftepring will arted to equal numbers, though they appear only us three recognizably distinct classes normal pool and hacmo philus mons, and normal daughters of the latter one b are boroty goten, but the other half are beterozygotes who in auten und an thnamit tho dixalke. That is to my Doral and haemophilus appear to . 3:1 rato, but this ta pot dustributed at random relative to rexu hart been the ratlos canaldered to the previous chapters Oo the contar ·TII GENETICI OT #EI 41 half the son but none of the daughters miles from the whoormehty (Fig. 7). On the raro OC OD when u heemoplo madla, hl wito Iluxully be normal. An her are therefore curry , whilo ball ha husband's spam Il contan Y-chromo kome od half and necesarily carrying h All tho children X Y XX H folie Roc The royale! XH Y БЈх HH Н] H xx xx, Y X YX huma 7 Total es balso the I-chromosom or betwo with dombout dmcar anul batawy o TOMAT. The product bescopbile a) Larned to the now palnog region of the X-chromo con, and are to be puncondition (H. The I-crocoon minded, the X-chromoo are not w thereforo bo free from the diacuk, dnes tho mom will inbolt no X-chromosome from the father while every daughta recetra I fra bor mothy Horor the daughters uro all beterosyrota, onpable of transmitting the dieren to the manner already described. Here beterosyrota uod bono- Tygoto rpeguto in equal numbers but one mort, relatir to res, doce the former typo includes males, aod the latta fanalan, only ·GENETICI TOI VEDICAL STUDEXTO A murange between a beermophiliac and I arrier aboold produce all lour type of children lo que purbert, acou cons and hemophillas sons, Dormal (but heterozygos) daughters and haemophiliac donghten. Hovore no instance of truc female buanophiliar has ever been recorded, though pamages of this bod oro aid to bere taken place. As the character les ressegir, two dota of tho ene ure DCORT for its prodertion in women, and it is pouble that such idiudub annot turtive until birth. The details of thos form ol segregation will be studied later (pp. 4-5) in relation to a condition in which all four typa co actually bo obtained It le bugtaly important to notice that a normal woman CA trenant haemophilia whilo . normal man annot do for bo pomerc only a anglo X-chromosome, carrya A med wboth a member of family in which buenophil occun may party in cooidence that his children will do inberit the disorder it be himself bo healtby ID dmiler er cumstances. wouuan ao bo giren no ruch wunder DOCT? woman who has . bacinophilies brother shock reakto that the chances no qual that has children wook completely cape the docus of that she would paw it on hair of there. Her Wetal dangters would be healthy though corner, but ber haemophilim soms would due at a early age. Furthe should a maternal anche bo. bomo philies, ato muy alto be carne Coondamy the local the only the chances that aboto heterozygote urocrt dently reduced by bell for ach generation saco the worl recent occurrence of the disorder thov uro ooc in hoc ff who has beemophiliec uncle, ono in eight if she bus. becnophilias great unok. Yet the autence of normal brothers and imda, lo the female ine, in generation heeguunt to the lut occurrence of the disorder may ! mindently, mumeowm, fabrly dbpose of the pobility that I woon b. artie It would not be unreasonable to conader her u tree from the buenopbille geve It the pombor of much commal brothen und uncle amount in all to dobi of mort any roman who belongs to a Inmuy in which ·THE GENETICS OF SEY 13 homoplita is known to have occurred should arduly codile there fecta before she contemplata manlage The inheritance of haemophilia tilanted by Qucon Victoria and her family Sbo mu hoef normal but a arte a huconophile Or ber four fons, three were balthy and Do (Princo Leopold) muhopophilltoo who actually lived to cootract marriage and produce a daughter and porn thurdous mon. The occurrence of tho dimork unong ber daughter's descendants has become a matter of history It will be rolled that the present English royal family is not publect to hacmophilia daco King Edward VII, being bartmal howell, could not trungnit it. A recood and much nerer type of heardophilia abro odsto In which the symptomes aro smiler in Hd, but muder Adicted individuals oro Dot katoanly inconvenienord by ther decem and, though dight blows may roult lo con Adomablo brusing they are able to land nearly normu hrou It L pot urcarodablo to intipato the furvival of femalo homophold of this kind, though tho polnt doch dot seem to have been establiebed. Thiba mild haemophila ta mbanited 2 c-linkod receive in the sumo way u tho more frequent ovete fama. Horwore daco the two types retain their charactaisten to the diffaent members of the famillion while they cous, thoy cannot bo attributed to an hention] Bone with vutable dilecto (pp. 20-9). It Lorensonablo to coa clude, therefore, that the mild forn due to another alldoccorpb at the hectophile being in the bacmophilie eta are bemboo of multiplo allelomorph sata Precio cvidence for this rhow to locking, but its truth appoun highly probable A purely analogow condition, suled haemophilie A, aloo beon reported (Lovit and Wilcon, 1930), It seems to bo accomively rare, und dition from the true becomophila both la ita phytolog and its penetla. In this discum tho structure of the aplilertes la defectivo It be Dot un amplo of som Hokep, being autoromal and destilbed s'dominant But the latter hateront la Inscounto (p. 17), doo Do homosyrotes have beco wailable for comparison, it li Dot ·OEXITIQE TOL NEDICAL ITUDENTS known if they would resemble the beterotygotes or on they anastUntil further evidence is a mullable, bector phile A mut be regarded us beterusypou condition Au ready mentioned, certain upects of ror-biaky cannot bo studied on baemophilia, in which allected emnet are not know. They can, however be asumined to al milde and commoner wilection ordinary red-greca colour blindnen. In England this oscun in about 5 per cent o mala and in about 04 per cent of female. It to lpberita unvextinked receyelve in the way just daalbed (pp. 40-8) to that only thoro (estures not preriowy orplained will not be compldered. I. colour bllod man murrles a woman beterotypno to colour blindnes, normal and colour blind adinduula wu bo distributed equally umong both male and female of spring the normal females being all betatozygotes (Fix 3). When colour-blind Cemalas marty normal mala, all the po naturally receive thefr only X-chromosome croth their mother and thus carnea tho gedo (c) for colour blindneth The daughten obtain an chromosome from both parents that from the father transmitting the partial elecomorpha (C) dominant in ellcct This all the sons are colour blood lico tbctr mother und all the daughters anu pormal like their father (though they are beterdaygoton: thib is called the To inberitance. On the rate occasions ben two colour blind parents marry all their children munt be colour blloch Theto la fome evidence that the proc tot colour blindern 1 pot fully recep, so that wometime the condition ut lenet partly expread in the betaorypoteh its troqueary in women in therefore sbore expectation (pp. 291-3). The genetia of colour blindneu erophanto the important fact that thert u Do inberent barrier to the occurrence of Hlinka charcter in both were. This is in contrast with sox-controlled inheritance (p. 81), in which the charreter Coocare are lumuted to one sex for pbypological rah Loxera a linkelcharter appeur soore frequently to our sex than the other. It receive, they are common la the male i dominant, in the female. The relative proportion ·THE DEXITICS OT SII o Hacomed on pp 191-8, but tho mero bot bobvioul. Fa upene recensire allot manifesta Atwell whenever proment to the male, but m the female It is dependent for prendon upon the denda chence of distribution to the two X-cloumporoma of the same indivdual Yith dominant хү XX barbec (heterotyrote) focic sxc X х cc clc с xx Y X abour ad abour bed M. Total warlos oth X-dacomo COM to bet with root character and LOT me. The protestay pour blad med be the scopertang porn tube brodog, ode to the porno mobilom (TY-OMOCOU RT beded, the X-bromero are not -linkers on the other hand, the presence of the two X chromowotna in the female allow . pater opportunity for the occurence of the gene Inhaltence of the typo b vary exceptional, but . congenital abuence of the incitore provides cumplo od It to which, however the beterosyrou a prendon ta udable. Its behaviour au rodily be worked out from the information already provided to this section, ForDembering that the heterosyroton Il bo locoded in the desa manilating the defoot. Honore it be purth while to ·OLXETIC. TOL NEDICAL ITUDEXTI koow if they would resemble the heterorypotes, or em they can onist Until furthe cvidence bruikbk, been pbiu A must be regarded us a beterozygou condition ds already mentioned, certain aspects or ser-loby cronot be studied on becsopbillig, in which allccted coal ko not know they can, borrever be cumined to all milde and commoner atlection ordinary red-green color blindnen. In England this oecun in about 4 per cent c males uod in about 04 per cent of females. It br Inbento Marx-linked rocenire in the way font doncribed (pp. 40-5 so that only thou faturas not previously explained will pon be comddered. If a colour blind med marrin a woman heterozygou to colour Wundra, normal and colour-bund individuals wi bo distributed oqually among both male and femak odleperiod the normal lemnule being a beterozypoten (Fig & Vous color blind females marry Dormal malah all the op naturally retro their only &-chromosome from therr motor and thus carries the perio (c) for colour blindoru. The Laughter obten an X-chromosome from both parents that trom the father transmitting the normal allelomorp! (C), dominant in elect Thu ni tho mans are colour biline like their mother and all the daugbters wo normal liko telo father (though they are beternzygotent this b culled To mberitance. On the rune occasions when two color blind parents merry all their children must be colour blod There's some evidence that the gene for colour-bllodeon is not fully receive, so that sometimoon the condition at least partly opened in the beterozygoter. Its frequency in romeo is therefors above erpectation (pp 191-3). The genetic of colour bundoca emphasize the important fact that there is no inberent barner to the occurrence of los laked character in both sexet This is in contrast with KI-controlled tobeltance (87) in which the character concerned the louted to one son los pbytologrou IKO Lovevo na linked characters appear more frequently in our Ker than the other it recetare, they are commoner los make; li dontant, la the femalc The relative proportion ·THE GENITICI OT ILI to documed on pp. 111-, but the mero fact is obvio Fa poc recero in effect muntrasts Hell whenever juraent in the mal, but in the female It is dependent tu apiention upoo the slender chance of distribution to the two X-chromokoma of the mum. Individual. With dominant X Y XX coturbed Hellcc XC Xc CIX cic с X X colour bed X X abord Rod fennt Total lobo ta tho I-cron up bemu vide mere barcher and beter mm The pen producting molour bathed in the competity repro of the Lebrood mod nomine to the band condition (C) The Yumovome ended, the Yorum mbot mez-linkage, on the ther hand, the presence of the two X chrumporomia to the female allows prester opportunity for the occurrence of the pena Inbaitance of this typo la very cxceptional, but a congenital hence on the indeco provides an cumple of it in whlety, bowever the beterosyrom a proudon ba nudebla Iba beberlour on roadly be worked out from the information already provided in the section, remembering that the betervayrotoa m be included in the danes manilastlag the deloot Bloweve It Is Torth wble to ·OXMETICI TOL MEDICAL STUDENTS draw spedal attention to two of the dtuations to be revealed when thus analyd is onderteken. First, If un affected man marios Dormal woman, abecote Inheritance to the oppouto direction to that described on p 14 Ocute all the daughters Inhalt the deloot whilo ll the poor uro Doral Secondly when an affected (boterocygots) woman and normal man, normal und abnormal Kons, noumal and abpormal daughten, will be produced in equal numbers, for all the children receive one or other of the matemal X-chromo- KOME. Now it la important to notice that this particular remalt is not dutingishable from doeninent autonomal tnhantance, though the trademiedon of the gene in other dreomstances will clearly indicato ita sa linked naturt. It will be realized that all tho normally was linked gaan being thouo dtuated in the replon of X not homologou with material in Y (F4 , 6-c), aro Inked with one another Crondng-over between them to of course ponublo to the femalo, in which this roction appear twice, but not in the malo, in which it ocown once only A common affection mode us colour blindnew cun bo used in such linkage studies with tho tarer sex-Inked characten, and the Holego relatione between it and haemophilie bevo actually been estimated (Bell and Haldane, 1907). The crow-ova roluo proved to be about 5 por cont, to that the the two genes aro situated clow to one another (b). Partial Sw linkage Gener dtuated in the bomologous replan of the X and Y-chromosoma (Fig G, a-b) datter genetically from the ordinary moi-linked type, dhammed In the last section in two respecte Fint, they can be trade ſcored between these two chromonomes and, secondly, they porta allelomorpha to both ones, instead of lo the femaloonly Thero ero of course equelcom quences of the cartoon of banologous material at identical bod in both types of KI-chromosome, but they have somewhat dierent fonctio alocta Wat ther coading over antirdy unimpedad, u to giro e CO Y of 50 rich goe could not directly be distinguished from those curled autosomally it on the cootrary crowing-over between add Y werd very rare, ·TILE DIXITICI O JEI 47 u to escapo obseruation in adinery Investigating, u dom nant partially rex Intod gee dtuated in X could not be dastlagubhed from a dominant abowing total sai lomlage. In dmilar circumstances, I recently could not be coatud in this way (see p. 48) owing to tho wood of the two propos thons jut rated that I will pouco an allelomorph in Y u wel u in X. Purtul Ke Tinkage can now be Illustrated by implan Retinits pigmentou may be produced by the action of any one ol at laut five gore (p. 75). To other uro partially Rex linked, ono being dominant od the other reoe dro in dilecto They all giro do to a pomerhet vadable group tymptom. Thero Loctudo night blinunch and gradual contraction of the risael Beld, often leading to total bow of sight. They are morated with an attenution of the retinal blood-vesels and a depodtion in the retine of pigment which hou migrated from tho tapetum. This is vlublo with the ophthalmoscope Il dominant retinitis pigmentowe were totally sor Inked, men who matter from the diverse would trant it to all ther daughten und nobo other mons. Actually however, they may carry tho pero respondblo for it ditha in thelr Xother Y chromosom. If the former krinkage of the normal typo will ma, cicept that occdonal attected 100. will appear onmg to crorangrover between X and Y In the latter dtution, with tho gero already in Y the one will chiedy be affected and the donghten free from the air ben. But erceptions will also urlac, leading to the production of few nammal poos und effected daughters, owing to an faterchange of the gedo in Y with Ita normal kelomorph in X When a woman rullers from retinitis pigmenton f tho Hod now under diewon, aho will ahoort aayu bo botero Trous for tho gano producing it. Her children will includo both pormal und lected sons and devguitects the lour types appearing in equal numbers, whether crowding over oocur or not. Poe that process merely transfer to rene from one The munted to Ybo poloed vtth total manera that bromo, Pr 11- ·19 QIXITICI TOT MEDICAL STUDZYTS to the other of the maternal X-chrononoma Corcquently tho autonomel, the partially a linked, and the totally cat hoked conditions are not distinguishablo when a gente dom! dent in tiect is tranmitted by I women. Tho analyds of a recente partially rew-bunked conditico u Uttle low omple Aitected individuela muut roodve the gene rorpondblo foe it from both parents. In the mother it must be carried in an X-chromosomo, in the father it may be ourried dther In X or In Y Condder these two altemettre Il do croming-over oocurred, half the daughter, but some of the moou would be of the receive type it the gene besed in the paternal X-chromosome, but it in the patatul Y the roverso would be true. But croeungover may trunder the rono troo ono petanal tox-chromosome to the other landing to exceptions that is, to the appearance of the recendo charucter in oondionel won on the one head or in couponal daughters on the other Thus roceed to partial was bokage will superfically renomblo tho autosomal rystem. From this it can bo duringuabod by an amciation with som within gom fondu In nom of thome, allooted males will be rare, and to others affected females. Thu it is only by the analys of induldoal famíly records that ruch inbeitepoo an be separated from the antosomal form. Were the cutes in the population wbolo to be pooled for study the excew of males and or females would balance ach other to that no indianto al mex-Linkage oould be obtained Seven recendre pathological delecta u Dowborn, aran good evidenco prerumed, to be partially say hnked. There must briefly be described. They were an originally regarded u entomomal receives, but it u pow clear that thoirt fixo are assocated with me, though this le rather los certain for tho last two of those to be listed. (1) Receudyo retinita pegmentos present the me fontures u the dominant type already described. There lots lo mother recendre, but into some form, which is clinically distinct from all other place, in addition, it pro duco data ·TEC GRIETIGI O1 SEY 19 (7) Xeroderme pigmentorum fe condition in which tho 100 exceptionally retire to light, owing probably to como metabolic disturbanch It bully recognlable a few week, or months atta birth Eqposure to sunlight aus reddcoing of the fra ud hands. This is folowed by the development of To freckles which do not dlapper oven when the Kan is abfelded from the light for long period. There freckles become larger mere numeron, und mare decply pianoented. Lata werte ake and patches of abun becomo atrophic, whilo corral ploems make theft appearance, to be Lollowed by opeditia The patients shon stroog light, eod though the skin may be unbealthy Over most of the body it become growly abnormal only in the aposed eren An attempts to ward of tho ultimato consequences of this does aro unurang money or late multiple malignant charges take place to thouldn, the confunctire, or the cornou These wually are too to bolcelled ourdamas with only. Vay mal tendency to metastaste. They can be kept to check for u toe by repeated operations and redfum treat ment, but eventually they becomo uncontrollable and the patient dia dancer of the face It uppern that reroderma pigmentosum is not quito recerdve, for there bendence that the heterozygoto may develop erreptional treoklmg It is doubtful if i Vary banly freckled indiyxtual abould bar children if a momber of a fanily to which perodam pigmentoqum bus occurred un questionably mich a person should not marry a relative (pp. 1348) (3) Congenital total colour blindnom boas crceahogy rare hata wally wociated with Furious minor ocular deferte Its much more extremo condition than ordinary red-green colour blindnes, and the general colour perceptoo alaust fouy importd. (4) It bas been shown by Vether und Philip (1010) that hero-lip and det palate is . recentro coodition which can bo produced by ather of two genes baring appareatly dmilar effects, One of the ta uutosomal the other to pertally selintol ·48 QILITICS TOR VIDICAL STUDENTS to the other of the material X-chromosomes. Consequently tho autosomal, tbo petely kez hoked, und the totally nar linked conditions are not distinguubeblo when a goa domipunt in citect itnnitted by . Tromen The analys of recento partially ke linked cooditton 1. httle less Emplo Afected Indunduals must receive the gode responohlo for it from both parents. In the mother it must be carried in an X-chromosome, in the father it may be acolod ather In Xo In Y Condda those two alternative If no croang-ove occurred, help tho daughters but Dodo o the romi would bo of the recoedve typo I tho gene is curred In the patcm X-chromosome but it in the paterdal Y the rover would be true. But cromong-over may trandar the gene from ono paternal wa-chromosome to the other landmg to acception that i, to tho appearanco of the recontro chancter in occdonal song on the one hand or in occasion daughters on the other Thus reocadivo partial ni linkego will aparicelyrekcmbilo the autosomal system. From this it can be dutingibed by an amodation with I whin guon fasellus. In mod thers, affected males will bo mereand in others allected females. Thus it u only by the analys of individual family records that each inheritanco con bo separated from the autosomal form. Ware the chose to the population wholo to be pooled for study the crow of males and of fernales would balance each other that do indication or sex linkego could be obtained. Sevon rectuvo pathologloul ddects und now known, ON good ovidenco preromod, to bo portully re-linked. There must briefly be described. They were all originally regarded u autonomal recerdves, but it is now clear that the first Ayo aro wrociated with me, though this is rether hem contun for the last two of those to be late. (1) Roccave retinitis pigmenton presents the same features us the dominant type Wrendy descubed. There aid also another recerere, but automomal foril, which clinically dbtinct from all other since, in addition, it pro docu dators ·chromobowto The THE QETETICI OT IY 31 A plated in Chapter I, the croutover value prorida un state of distance, so that it is portable to coostrict map of the pating portion of tho ka-chromorome. This has been done by Haldane (1830) reo hay o it is the oaly hman chromosome map oturarallebla Though somewhat tentative, It Indonto the sctual ander of fire of the Inown the upon the chromosomno ud poorida an antimsto o their relative distances spert (). Total Solbage in the Photo The Doohomologous region of the human Y-chromosome very Rp x og up 14 17 20 Tea. Hon the patitor portion of the home Theroperwted on the band he may be other pert of the long noo perting method do the short bon paket without pollutions w polot where the people and the pelo uplo wout (tt-total color bland Groc par-Ogwobr qipet detmoly bulon ud-doro eodoro rotboll pintory After Halden Ahort, wo that it must carry relatively atruneły for gener Such bave been detocted to two or thrco instance one of them be respondblo for the production of webbed too but It bakpown that keeral other genere, cuorlod ceowhero on tho chromomomos, may also rive do to this condition. Ao additional tratanco i prorded by un atrordinary dicero (Ichthyoo hyrtdı naslo) in which the skin became thick, mered, eren bratly and backened It forms a tough altido which is shed at intervak, apontog akta which ba at Art Dominal bat soon becomes thickened pain. The effection bu boca socountad coly o . doglo family Gong carded in the doo-palring region of the Y-chromopomo ero puwed directly from father to do and, of course, ·59 GCXLTICS TOL MEDICAL STUDENTI can only lost moles This u the polo tance of inheritance ratncted to QDO I nothing comparable with it has been found, por is to be expected, nomen Charcten which aro opreme in mulos, or fempeles, alone may be inatence of Ki-controlled inberitanos, dependent upon to curled anywhere on the chromosoma (p. 89). Hovera thome which are also trenumitted only by malas must be doc to gehas cured in the bon pairing section of the Y-chromowome. Thus i fow chance must erst which are pusod only down the male lins, but female inhentance of this kind bot know II. THE AI RATIO The Ample distribution of the X and Y-chromoNOMO would seem to care oquality in the sunber of male and femalo concepton. This apectation is not tulilled and, indood, the relative proportions of the two Koid very at different tima of life and in different circumstan.com. There forts, when analysed, thiron bught upon woveral metal and medical problemi. In preparing the following curvey of them I have drew largely upon the accellent account of Crow (1037), to which refere000 hould be made for more detallod Information The intlo is crually expressed other us the number of boules to our hundred fanales, or us the persentage of malar in the population concerned. Thun kerabo of 100, or of 60 per cent indicatos numerical equality Covoquently mala art in excen wben tho ka ntiob high (over 100, or abovo 60 por ant), and female aro m cxced when it u 'low' (under 100 or below 50 per cent) The sex ratio ut concep tion and at birth is called the primere und the secondary' Hinto respectively That at ktuel maturity is often called the tartiary' ki nato in other wimals, but in med the aprension u too Detect to bo metul. The Report of tho Registrar-Genenl for 1935 show that In England and Fala there is a slight acea of malo blithe the Keoppdary Kinto being 103 100 (81 % per cent) This is programarely reduced, so that numerical equalty ·THE GEXITICI OT IBI to reacted in those wed from itteen to nineteen yeur. In the past Iresearly 4-group of twenty to twenty four yeur, tamales predominate for the and time, and they become proportionately commooer in the population until there are sotually twice u many women us Den mong thon ged cighty firo und OTE The dilatntial elimination of mala odlated by theto data in apparent abo la pre natal life for tho ma nuo of foetines dying during the sorenth to ninth months of Intru utarine life a higher than at birth, being 110 ( 53 8 per cent), Lodeed there to evidence that this is not only maintained but tatoofed pering backwards towards comorption Thus the axratio alinlanb dying during the first year after birth a highest for the very young while, socording to Crow (1887) * highet alo mong early than anong late abor too. To may fairly coachoda therefon, that the primary *trato departs widely from equality in the direction of an eicer olmalar It will now be convenient to tady somewhat further the rotults of this trend, then to seek in oplanation for it, and Analy to cocuider the problem presented by the high primary Orto The lova viability of mula then of females to raposable for the way in which the mi rabo dullen m torging arcutano Ance, withia cetain lonite, unfavoarable cooditions tend to uccentuato and la rourablo opes to make There is ample opportunuty for the secondary sa ratio to bo affected in the way dnce, ou tho vents, only 76 per ont of conceptions yield llvlog afturing The secoodary moto . highest among first bora chldren, rioco abortion and micrrlygo en relatively mora frequent in large then in all femlich It is lower AMOOR the children of old than of young mother, for with addon to the intamu carroament become la faroutable for the foetos. As abortion 1 more frequent fa urban then in in communities, the roctodery w nato blowo la towns than in the country Por obvious rood ales, abortion and ·Otsirici for WIDICAL STUDENTI atil births are particulady common in respect of llegitimate children, whose rccondery ko nato de consequently low It u otten rated that a relativo fnctas in male burtba tako place in time of this be a fact, and the evidence for It does not appear to be concluare, It is powłbly choo to the wider pecing of births owing to absentee husbands. For repeated conception, following too npidly upon ODo anotba create an unfavourable environment for the developing foctor However my detectablo effect of this kind epean rather to follow the conclusion of hostilitia. Thus it poky well roult from the fact that there be an excess of first bon children at this time (wbo, u already mentioned hero bigh sex ratio) owing to the frequent postponemental martlagt during war Al factor which tend to roduce tho standard of living tend also to lower the roocedury ski rather which la bigber in the upper and middle clamos thun amore unabled labourer. Consequently w stressed by Crew changes in the secondary ker nato can be used u an inderal the offectivenem of social services, runh us alumn Clourico and attempta to improve the general health of the community All these facta ero dependent upon the higher death-rato of malca then of females, the bod's af which multa inqury Clearly the more pored and dangerous lire led by me then by wonen must contribute to the excess of the latter in the higher age groups, though it must be remnambered that deaths ut childbirth tend hoevily to the opposite direction. But auch condderations are loupplicable to fio fancy and to pro-natal adstence, so that other and moro fundarruntal cartoon be sought for the phenomenon. The XX, XY chromosomo mechanitin itself constitata system which acta tarounably upon the heterogenetke I. As will be platoed In Chapter IV dodrantageous gond tend to becomo rcconive in elect Now if we cadudo the small soction of x bomologout with Y it an be mid that rocetiro ki-linked chercte wolnyi apre lo men bat tay rarely in women. Tbo reason for this obvious The repudio sex-linked genes in . dnglo X-chromosom ·TII GENETICI OT JII 60 cannot be opposed by a dominant partner u thay - wally be when two X-chromosoma uro present (reo pp 10-1). The region X whiloh so homologous with Y must contain many modreds of gee, . for a which will almost catainly bo to the rooctavo stato in any indinduel und apable of lowering his restance to discuro or reducing ha eficiency in other way It will be notioed, bowever that there oondderations upply not to the male u ruch but to the hotarogimctlo KI. Yet It is found that the male bull tho more banvily diminated in those farms (ey birds and Lepidopten) in which tho feculo is the XY type, but to be atent than in the roverno condition (Crow 1937) This mgruts that whilo mi-lmlango kuuro of the bowe Vlability of tho malo in man, It b probably not tho only one. Somo additional agency. function of rex Itxell, must also contributo to it, and very ponsibly this is to bo found in tho higher bacal metabollon of Der than of women, whilch llocta both the young (Benedict and Talbot, 1991) and the adult (Benedict and Emmer, 1915). It is probablo that tho greata cxpendituro a noi by tho malo moko hum bom restant and more liablo to death than the female, a view which is supported by purious periments on Lower forms (neo Crew 1937). There remains the atrordinary cocon of mala at conception, despite the operation of a mocheptun which appear o catainly to ourre tho numerical equality of the Kics t that time. This anomaly has mattulactarily been arplained by L. A. Puher (19506, pp. 141-3) during the course of his valuable analyus of the elect a natural selection upon the Kinto Bdore moviewing this, it to Decorary to połot out that in lower farin geoes are quite well kon which act differentially upoo tho and Y baaring gamoto pro dooed by the beteroquetio km. That stadied by Gorbeamon (1009) in the fly Drosophila peado barve may apecially bo montioned. The eliminutos pourly all -bearing pame and b quibo common in nature. It is highly probable that such gena uro of almost untren DOCUTTEDC, so that even tho poimary tatlo in rurceptible to reloction.

·BO QIXITIOS FOR VIDIOAL BTUDENTS Bearing this fact in niod, the course of Fbher's argument #clear He points out that the parents of almost all animal cipeod outament, a well u time or activity upon their young before there become lodependent Natural relection will act on the parents to make this expenditure as cicient us posible. Now the reproductive vulne of an entire generation of attapang at the time when parental Hability can be the tame for the two kia whatever their proporton may be Hinoo ach ks popplia half to the ancestry of future gener tomt Thu natural election will wo adjust the ri nto that the total expenditure incurred on behalf of the two more sball bo equal. But ruch peodituro must includo not only tho parental outpat upon thouo individuals fuccesfully reared but also that lavabod, and wasted, upon thoro dying before It ceases, so that in man, whero moro non ero eliminated then danghter, malas are moro capenave to produce than femalen Tho averige apenditure to therefore les for each boy born, and greata for ach boy reared, then for grb at Corresponding stage Consequently In view of the quality of total expenditure, natural election must lead to a condition in which boys are the moro numerous at conception to sofficient extent to make them more numerou at birth but let numerous before the end of parental care. The montlo at the timo when this car will not be affected by abeoquent di tercatul elimination, but auch elimination will have modified the sex ratio when actual matunty is later reached. However u the total reproductive contribution of the two main then will equal, the murer sou will be the more valuable, so that more intense selection Ill be exerted towurde its prekrvuton. Thus it appears that marked Inequalty of tho ba natio at maturity ill only wiso if thu condition is of dedded adaptive spiflcance. The system bers outlined to of tho whest application, and it will be observed that the human stortina falla rather accurately nithin the limits which it Impore ·CHAPTER M HUTATION AND THE NATURE OF HEREDITY 1. MUTATION KUTATION MAY BE defined us tho inception of hettablo Furlabon. Changes in the gene themelye, or to the chromo- Home which carry them, may be reflected in the chancer of organiom, outing it to dillar from the normal foci. Bloce much changes affect the hereditary material thoy aun bo trudmitted to ubacquent geretution, that the chancton which thoy produco ero tnborited. It will be evident that mutabons may not have en immodlete fnflueno, u when one member of bomologow pair of allelomorpha matata to produce a gens receive in ellect. Very genet tou may then clepo beforo homosygous recentro arlier wo that the pearance of an individual ponendng a novel toccavo character may indicato only the occurrence of mutation to the distant past. On the other hand, an Individual pomicutag dominant character Dow to the stock which to being investigated usually demonstrate that . mutaton w taken place in tho fermoel of ooo at ita parenta It l desirable to adhere stoletly to the definition of muta thos adopted here. Mutations are sometimes defined u abenraa in the genot, yet thuis bar too restricted, for chromokoma modiboutions bed aloo to inherited nation Furthermore, the concept that como diventy acists to tho germinal material implied to all theories of inheritance, and oo must be the Inception of mich dvondty It should therefore be pouble to discue tho part ungablo to mutation in the nurows bereditary systems postulated at 000 tm ar mother and to compare it with that which it L DOW actually known to play It be trafortunate that the term mutation totoo nuo to tvo k fint, for the actual change in the hereditary matalal; scooodly and qmto incorrectly for tho repult of ·KS OIXITICI TOR MEDICAL STUDENTS that change. For instance, the low preciso writeni on genetiss quite commonly rda to u rere which besten during the coume of paimental work u. mutation. For thill, the exprendon mutant gene which may be madd to give niso to mutant characters may be employed, and is morception able. Further the word mutation ! one which long intedata tho development of modan genetics and, liko many othai Dow scairtely standardised, has come with it a tradition at iporect nuge. Thw Dove character was originally described as a mutation though it might in realty be due to recombustion or oven to environmental yurton. However when . term bus acquired a definito technical meaning the fact that it me once employed lens strictly is not an acu for wang It loosely to-day Were the mos current Domenclature both in biology and in medicine would have to undergo . for reaching and wally unnecy roviaon. It should not be clearly apprecated that neither a gono por a chancter can be called a mutation, only tho act of change in hereditary unit aan so bo described. It has Jroady been indicated that mutations affecting the hereditary material u we know it can be rub-divided into changes in the genes and to the chromosomes. Theo two aspects of the proces must briefly be considered. Geno-mutation must be due to chemoloal changes occurring at particular loci. There may be of now Hnde lerding to the production of a series of multiple all dacorpbu. A for us to knowo, the mutations at a given locus are limited in type for they produce alterations in the most of chano ten, often of i quantatethro nature. That is to my we do Dot And a gede controlling for cumplo, cye-calour but not hdght mutating to a condition in which it controle haght but not co-colour Thus the chemical ribstitutions which gedo an undergo appear to be restricted, and it u tble fact which enables us to my that the allelomorphs determine contrasta chancten. Chromopomo mutations can be grouped into two main dan boormalitia to the distribution of wholo chrono tome, and chromosome fragmentation. The first of the ·8 VOTATION AND ALIIDITY aun in bo obdivided into polyploidy in which the whole do chromosomes is multiplied, and interoplody, in which chromosome may be added to or lost from ongle chromo PHOO-pair Polyploida etro from falures to coll-dividon during meloda, leading to the formation of a gamoto with the diploid (unreduced) chromonomo number This, on fudog with a normal haplovd gameto, produces triploid wroto pomem Lag thres, tostead of two, seta a cromosomes. Further Irregularities, auch u to foon of two diploid gametan, may lead to tho production of todividuals with four chromosome notat (tetraplolda) « are higher chromonOMO value. On the other hand, haploid mdividuals may sometimes who pomeng angle chromosomo wt only us in the gameters but this cocin by different meam, through partheno genets' A perinatopoon which falls to achievo tartillo thoa 1 condonally summate un cge to develop, and the Individual which it produces will pomeni dnglo material chromomomo met only Polyplois bavo not been enouun tered to Van and Indeed they aro almr nro in animals, though they are important und widespread la planta Heteroplonda cu rarely establish then cires, for the addition or low of ringle chromosomo has greater and moro bermful effects than the addition of low or completo set Thea b duo to the lack of geneto balance which enges from quantitativo pritious in part only of the boroditory material. Doubtless the condition be very rare taman However it is obvious that the addition of Y-chrocnonomo will havo far les effect than that of an roto omnes for part otho Y-chromosome binert, while auch geros us it cootalos monot bo necesary for Ufo doce women and without that. Thoro la Ladood momo cridence that the two buman X chromosomes here occasionally becomo attached, so that both must paw into . Anglo paineta When this blottilised by en baaring sperm tho itpulting wygoto die oring to the lack of geolo balanco whbob , bat ben fatilad by the Y-baring type it b car that beteroploide porning threo sex-chromoms (two done Y) an ais, eod ·OLXITICI TO. MEDICAL STUDENTI thero lo cridence that they have actually done so in men Thus of CUTITE produces . Ten of kalibugt, Anco the daughten Taro both X-chromosoma from their mother and tho com receive ther only X-chromosome from their fatha At least one pedigreo of this kind has been reported (Holdang, 1982b) in which the normal suodation between ordinary recoedyo colour blindner and bar wus rovered Chromosomo fragmentation may lad to the loss of part of a chromosome (deletion), the partion which remains that which contains the spadlo attachment However the broken fragment may re-attach itself, tho wrong way found flavcrtion) or elo to the homologous chromowano (dupli cataon) or to . non homologous chrononome (translocation) Such phenomena do Dot seem to have boen staded to mun, but they must certainly occur wd. watch should be kept for them. They would moet curly bo detected u transloontions to or from a voz chromosome. II. K Hoked groo weto obucited to become fully autosomal ln labertanog or the reverse, strong preamptivo cvidence of alch trang location would be obtained, provided that it were possible to detingulsh tho ocurrence from partial no-hukuga. It is important to notice that in other animale, od in planta, pumarota combined cytological and genetic studios af chromosomo mutations havo been made. Bar Instanoc, genaa bavo Occadonally been found crociated with the wong linkego group. In these circumstances it has often been powable to ko that one chromosom too abort und unother correspondingly too long, owing to the transloc thoo respondble for the observed genetic irregulanty Such obatutione prorido a remarkably complete demonstration of the chromosomo baris of baddity (sce Sinnott und Duoc, 1930 Waddington, 1039) Vary abort deletions may pino much the cloct or roho mutations, Dor an they be detected cytologically. Oo gazetal ground, it is not to be aspected that the majanty geple changes are due to in actual loss of antall, and baru bcvidence that thus la not so ·01 IUTATION AND ILIIDITY It should be noticed that motations, whether of the getic or the chromosomal typs, are stretly loulood phenomenu The occurrence of a mutation at ape locus does not elect the allelomorph, nor does it tend to produce mutations in the gend on either alde of H. This letter statement may porably here to be quohfied, once . modiflation in the fiect produced by the reader the locus of . mutation has been reported in a dnglo argentom (the tradt fly Drasopkla) On the other hand, it does not yet appear to bave been etablimbed that such go bero allo mutated. The alterations in tho character which they produce may be due to an interaction between their effects in those of the new mutant geno (Chapter IV. indeed It seems likely that this bar There b evidence that mutations aro lightly more frequent during cell-dıylalom than in the resting there, but they uro not to luct restricted to any one period of cell activity Nor uro they confined to the ser tract, but an occur in the body-cells abo (sometic maddior). This is more important in plante, whero roma tha thuo can give theo to goom-cells throughout hfe, than in animals, but it bu been widely established in both kingdom. In man, tho procen loof potential importance ince it may powably initiate e malit pant chango (pp. 03-6) An crample of it to probably provided by heterochromia ridha Of great theoretical importance to the fact that row midation can occur from the mutant geo to the allelomorph from which it wu denred from the boortel to the DODAL. It L caur therefore, that mutatious wo not ewentually do Aructivo changes from more to low highly organped rato or downrde from compounds poetending high chemical ceru Tho fature that out tion u we encounter then and of type antablo to iputate the reacts diversity of raranlm Mutations und aceedingly rare pheromone. Yet they are recurent, and take place with chercteristic frequeocios, being relatively commoner at man bod than at other. It I probably true to ry tbat quo mutation la milico Indirldin bun approximat Fenom tation-nate for ·QCXETICS TOP HEDICAL STUDENTS given gedo. A mutation-rato at 1 in 50,000 indir dans la exceptionally high end rarely exceeded. These values appear to bo approximately similar throagh out the widest mage of organisms, both animals and plants, and for this there a good reamon (pp. 79-8). Wo may bo confident therefore that they wpły leo to man. It , bow CTET . romewhat remarkablo fact that we actually ponto direct evidence of the human mutaton-nate in rospect of fow geda, The Knot upon which such information has been obtained must bdaily be foccated. The fint estimate od mutation-nat, hi man u obtafood by Haldano (1995) from study of haemophilue. It bas been pointed out that this s recruto vs linked docume of mo KVETO a nature that Dearly all hecnopbilled do without producing offspring (PP40-4). Two thirds of the X chromosome of the human nc oocur in women and one third in men. Ono third of the heemophilia genes in the population are, therefore, alwayı aposed to relection, and are Dearly always cluminated, while the remainder aro Dok Thom wero they not supplied anew by mutation, the disease would rapidly dlo out, andata alculable rate. The frequency of mutation Deceunery to maintain beemophila in tbo popolu Hans au therefore be found. Hilano mi able to show that the proportion of hectophillea living in Greater Loodon in 1985 munt te between 38 and 138 per million mulo birthi. Wyo may be confident that this proportions to equilibrium, conclusion tally accepted if no condor with Haldana tbo atuation in former time were this not mo. Suppono mutations were not making up for the koowa dimination of hecmophiluo, o that the bacoophilie geng bow cuting Tere daired from haemophilieg of heterozygotes for an arller population. Thirty generations yo hemophilus would bo 100 000 uma cammond then it is to-day and the vbolo malo population of England Fould be haemophilie at the time of tho Normun Conquest. Haldane alculato that I mutation in 50 000 indindul required to balance the elimination of the bucnophille gone, which therefore representa ita matatloc-rate.

·8 KUTATION AXD HERCDITY The study of epilola bu provided material for an torvertiga Honol mutation at another locu(Gutbar und Parrok, 1938) This doen one in which mental deildledoy unmociated with adenome rebeccom and other loin deteots (pp. 79-80). It Inbarito u un autosomal dominant, yet mumber of che ero known to have bed normal parents. It is highly unlikely that there represent failures in heterosyrous manifestabon, noe the agregation is alwayı vary courly marked. Such ponudio occurrence mut, in fact, bo muta tony, and Ganther and Penroso find that they take placo with a frequency whlah lo between 1 individual in 0 000 and 1 in 110,000 ol the population It ha most important to notice that noh estimates of human reno-mutatou do not represent an average but approach the uppa Kunit of its frequency For oldenco along the Hoo could not be obtained for mutation-nator much lower than thoro sotually observed. It is clear therefore, that mutation in man L of the wino order of magnitudo u that in other organis (pp.01-1). In those instance actually studiod, the frequency is dghtly higher than of tho mort mutable grona of Dracopilla (tbo porno for white cyc, with a mutation nato of 1 in 80 000 todividual) but does not all very materially boyond this. Noverthel.com, momo indicatoa of tho moro portal mutation-tate In man an occdonally bo obtained. Tho mala teated by med beemophillon, which k alleomorplabo to the Kyoto form (p. 43), oro handicapped to a comparatively light degree and often becomo parente, though they must coatributo somewhat loss to posterity then do healthy indinduak Thus tho selection operating unut this gene bo far lou wover then that gainst ordinary hecmophille yet the mild type is much the nurer Cook quently mutation to this pero must be toy much more uncommon than to the other hecmophila rong, and . troqnency of one in a mMion individuals L. probably an overatidate for it. Tbo Agnliono of mutatioarato will be moro fully dlactod in the recond roction of this chapter It be not know what agencies uro normally responible for mutation. Iodood caviromental Infococo un rarely ·04 QEVITICI TOL MEDICAL STUDENTI ablo to alect tho hereditary matall, and only those of the most volant und an do ns. J Muller nu tho find to abow that mntations can bo loduced by X-ray. In farorable circumstances, the mutation rato an bo inercured about 150 uma by thba mans. It is now stablished that all typa of sbart mye raduation are apable of producing mutation Xny of different lengths, ultra rolet light, the rengia nduo-active pubstances, free cloctrony (ray of radium), and neutrons. There yents are all equally effective to long - equivalent down (judged by bopluation rata) aro employed. Special Momance mut of Courto be made for thoto of low penetrating power particularly ultra violet Hght. All form of mutation, both genio und chromoucmal, oun bo nduced by these means, but entirely at random As with the spontaneou type, they do not cumo alleomorphilo ench of thong at neighbouring loch, to mutata. No mo agent tends to produce a given claw of matatloor, or to induce them ono locus rather than another, por aan the retulta bo controlled by varying tho doage or by any other Imom man. Many of the mutations which take place are the amo u those which have appeared spontaneously Others have not been observed ercept as the result of artißcal induction, but it a highly Improbable that there art, in rality noveltier, Au nich tratment increase the frequency of motations no greatly popo will naturally be encountered which have not yet been detected in normal circumstances Purthermore, reverto mutation and be tnduced by short-wayo rudleton It is found that the relation which alsts between the amount of radition und the mute of Induced mutation is of the simplest kind, being one of direct proportion A doubling of the douage results in the production of tnico us many mutatons. It is therefore porble to determine the frequcocy of mutation produced by my gtred amount of short want radiation. That occurring Daturally prove to be far too sorell to account oven for the minuto frequency of spoo taneous mutation. Some other percy must be responable for most of this, but ita Detmo in not certainly koord ·NUTATION AND HIREDITY Howoter como reda ure able to influence the general levd of mutation in the arpantem. Prerumably they place tho bareditary motorul to . chemie atoment which to motos totability Thus the mutation-nato ta in part gonetcally controlod and it is thereforo perceptiblo of selection, a concoloo of great importados It has now been pondblo to induce mutation by means of bort wart radiation in a great vinety of organlams both plants and animals, includtog inuects (Drosophia, Hebrobracom, and other) and mammals (mice). They all repond the dmilar way It may be added that in lower forma a mall inotauo ta the matatlon-nato bus renulted from tho appbom Hoa hertz but this is not likely to be an effective Agent to mammals und birds, which pomoc a constant temperature control. However wo can be cater that X-rays and radium Ioduct mutation in men, and the moformity of the cllect which there agents produce on the widest variety of argundum allow to realise with confidenco on ther Infidence on the human bereditary material. Since the vast majority of all mutations must decedy be hermtol (Chapter IV), that influedoc, we can be certain, L hed. Satiafactory data do not y t appear to be avullable on the proportion of moulages abortion, and still-birtbe among the otpring andrologtata. Depute the protection corded by modern technique, it te hardly poudblo that thoro coodition sro Dot in some Jight aice when compared with the rest of the population. They would, of copre, urino from the production of mutant genes dominant in eloct. A Tery different dtuation is presented by the recentes resulting from rulati mutations, and this matter bus rocently been ibodied by Voller (1841) The appoindce of the bomoaygous recendre type may be dus ather to the mutant gono meeting another like it, which had been indacod Independently or to the meeting of two gena dencended from the name original mutant. Vuller Investigated all tho upects of these two poolbllitla, ipołuding the frequency of induced mutation, the prin natural boormal types, and the degroo oltbroeding in human populations. Ile reached ·00 OLNLTIC: TOP PICAL STUDENTS the conclusion that even in the most dandy labeed groups of modern society receive gode originating froin nudition technique would retain latent for 200 and probably for kval thousand years Scare potential danger from the Accumulation durch gear in the population roue the lege xam but it cannot of burns outweigh the diagnostro and therapeutia benefits of indiatoa. Yet it & well to daw attenika to a {alacy which frequently fada mupport when auch station - this la crpared that the cumulation al harutul romandre asiang by mutatu, due in this bostance to radiatop thenpy can have a delete you intenco apon bunan evolution Unces llende Han inbeitano, evolution u pot controllod by mutation 1 The wordlation today may inces the proportive of diadratageous types pregadag in the distant tuture There will be mabject to counter-selection as they appear bat txy cannot fniluxe the counts of evolution Powerer when wo corakker the pomubile Conacances, both immediato and remote of the Luct that short mro nudlation Induca mutadone, the lat portance of weiding the ponuda during radiation latended Lor other parts Boede no Acklitional emphadu I TIL warun 07 HILDITT It is asumed throughout this book that haunaan inberitana of the Medelian type, although many other theories of heredity have been drancach Such an mimpton efecto profoundly the deduction to be dowa Iraon obserratious on inherited conditions ia masand the influence of the cavironment upon him Carracquently it is ewential to rew quote briefly the mala lina crideuce which can be adduced ka favour #larreaching & conclusion end to canada rather than helly than wu poneblo la Cuptor L bo what captial respeto the Vendelin syatan of beredity difter trom all otherä It is caury therefore, to cobart upon a short dicuboo whick, though theoretiel, ki pot topractical. lodead I do not see that any fiat cowprebetto Honor human fonctios an be attained without th. IR Soo Fuber (28002), aloo the wood section of this chapter.

·MUTATION AND IXLIDITY probos work I have cumloed the nature of heredity from no elementary point of vlow in nther more detall then an bo doos baro (Ford 1988). However those wbo require a tol ways of this abfect should coorolt the writing of R. A. Faber, ospedally ha tudamental mort, Tu Gedical Thury of Naural Sdnation (14000). Al bereditary system, an be clesfied u belonging to a fow besto typa, fact which greatly virta to the analyuta Fort, tnhattance may be either wboral or bomul It bus been widely held in the past that ODO BOI only cotnbutes tbo whole, a clue the greater part, of tho baroditary material to its offspring. Indeed the Law of most dillad countriem to-day ars, incorrectly constructed on the usumption of un cual and putand haredity though the concept of purely maternal inheritance hu been upheld from time to thee. In so far us it a poodblo to study the problem critically by obervation or direct operiment, no rapport for unimul tabeltanoo has been fortbooming thus the date of genetics todhonto that, in bleexually reproducing organlos, the two parents are equelly responoblo for tho bereditary chanctors of their odopring How to many forms, man for netance, are unguitable for perludentul technique while the bereditary control of the majooty of chancen far too complex for Ariet analyse. It to fortunate, thero fore, that there adeta metbod for uwcoing tbe bereditary contribution of the two parents to the widest kenn, provided only that it is poodblo to detect any maugnblo verlability to the character under consideration. I rder to the study o correlation between group children wd their malo und femalo perents respectively Conddo wny character outddo the scope of asperimental treatment human belght, for nmpke. Now it lo posible to alculate a correction pricina -hlah aprake the degree to which the variability twochaructersbunsociated 1 S ppare no obtam the correlation coeficients between the belgbt of a proop a father and their sons end, scoodly Por tipproposta pethod for doing so for lo eru barotidanther 1941, ·GENETICS TOL MEDICAL STUDENTS that between the moo group of soos und their mothen. These two correlaton coefidents mazare the tendency for height to bo koristed in parents and offspring Now of the hereditary contribution of males and femalo u du nmder the two correlation couillcenty po obtened will diller ognificantly That they never do so indicate that the Lather and mother art of oqual importance in inbentancm. In addition, it abould be noticed that companion of correlation in relative and unrelated person provides a proof of beredity and a measuro of ita intensity in intado outade tho scope of apartmental verification It bordent that tho bereditary material mut be trant mitted in the gam-cells. It may leo be uked, it ratrcted to the nucleus, or to the cytoplam, or be it conlod In both reglons! The mower to this question has just been given. Mala uod femalos contribute crectly oqual sheres to the Ducleoplaun of the post generation, but the amount of cytoplasm which they provide is vestly different. It is not at all uncommon for the female to apply to be children. million time u much cytoplasm u the male, or mort. Even tho mall human cg carries immensely more cytoplam then does the sperm. Were the cytoplasm to play woy agnin cunt part in beredity tho contribution of the two sto could not pomably be equal, which it is proved to be. The nucleonot the cytopları, is the actual pant in tranh mitting the gends, whether we can damonstrato tho fact by aperinental breeding and cytology or not. We can therefore limít organic inheritance to those systems which are boseanl and nuclear Having dono no, two ponible typer remets. Some sort of with, cotrolling the character of the ormanlan, mutt be trapimitted from parent to odapring it heredity has any physical bars at all. Further nace the charcters are controlled equally by the two parcate they must be determined by the action of pain Lacton A obrioca stoepika has to be made to almorally reproduce artule (con recodary condition) to whit, bon ter the wa watod letbe pucho. A amplat cytoplarla bat Loonwales Los but the rest eat focal leterou ooly ·PUTATION AND IIIIDITY 8 (allelomorpha) doved respectively from than Now when much pata are dediler (beter sygoas), Itan bo papporod athar that they contaminats and other wliess brought into the memo cell (blending in borttance) or that they remata permanently distinct (particulate inhetanool Numerous theodos ewentially depeoding upon blending have been adnanoed, bat particolate Inheritance is the Mendefian type. It mit dearly boundarstood that blending In thi KLO rea to the gras, not to the chancta which they produce. It ki commonplace to find that genetic factors controlling contouting charactent orok, totermeduto elect when brought together the character band then blooded that the red controlling then have not done to the demonstrated by the fact that the secoding foranstoss the contrusted typer crystalline out of the hybrid mature puro us they wara beforc, Cocquent upon wegregation. The genes havo remained distinct, whatever their effects have done, and this la particolato Inborttance. So long us it ba poodblo to proctaco F1 und Ps generations and compare them, It can be decided whether inhontanoo ba of tho Vendolan type For bonding leads to undfortalty while tho particulate mechankan maintains divendty owing to regregutloo. II, therefore, the Fl generation mors Triable than thos, the inbentanoo larained to blesdag while it is more Turiable then F2, it beperticulator Yeard thw able to decide wbether inbentanoo ts Wendellad En instances which are far too coople for factorial analysba. Freetonu, u ruci, aumnot dormally be studiod to man, noo they lovolto incent But the couential feature of them, to math of two heterosyrotes, de constantly obectved. Furthermore, the generation La marely the atremo tostance f the proposition that marnego between relations teads to vadability through the regregation of bomosyroton. Tho well-known tendency of reentro characten to Ppour more frequently wong the children of cloucly than of dhtantly related parents is an arpeempion of the apesty of the particulato mechanlan to promote direrity and provides arden.co of its operation ·70 QIMETICO TOR MEDICAL STUDEXTS Wc may therefore accept the conchonan that organla inheritance lo man ud other organisms ls of the Mondellen type A number of mportent on toques.con flow from this fact, but for of the only ure relevant to the purpose of this book, and there can be touched upon bat briefly With . yttern of blending Inheritano, loading to uniformity inherited nariability would be rapidly reduced et orery generation, actually it would be halved. In auch station w are faced with two alternativet ather the amount of inbertted puriablity must be minute, or else it must bo maintained by flow of matatlons to consdanublo u to counterbalance tho toiluence of blending Thit the position with which Derwin wu confronted in him analye of evolution buvod, u ít we, upon the coxloept of bleeding inbertanon It led him to mako carcful stody of organlans fn mature and under domestication from which be determined that thoy poden abundant nilability This, therefore, bo conoetred must be mopplied by mutatko ('new versations. Consequently be attributed groet raportance to all agents controlling that procen, ether its typo or its frequency Under a system of blending inberftanco tho Induction of mutation must be a matter of overwelming significance, wd Darwin wu perfectly carttot in adopting that yow but it vu faludy founded. Organio inheritance is Dot of the typo that ho mpposed, for it is particulates the contrusted liclomorphe da dot contaminato come another wbco brought together into the name oeill, and thetr sagte tion is suffident to ensure tho prokrvation of emplo varten thon. With purticulat inbentaner, mutation not only can be bat must bo (p. 7a) hundreds of thound of two lom common than Darwin thought it wou, and egenta control mutation are hundreds of thousands of times los looportant than Darwin thonght they were It L Dow pomible to consider the bearing of these food upon human latin Evidently we can no longe attach autoanco to those theories of human crotution which work by controlling matation. Such is the Lamarckdan involving the inheritance of the elect of we nod dan ·IUTATIOX AID IELIDITY 71 mbsequently ateaded to cover the tobazitance of those canctos which are nowly soquired during tho llo of the openim. Vesteal men may wel bo uked it wo ban boy ground for coming that the alleets of the virunmmt att Lobersted. The natura organic inheritance, limiting u It doa kedy the part unable to mutatlog, proctoda och a Thor It should further bo noticed that the concept Zeqatras to addition i qualtatto control of mutation of Yay renartable and Improbable Wind, ruch that the carton ment should so modify tho bereditary material us to city through all the coupledty of development, to reprodoco the une set of character which the original enviromental stimulus chanced to croko in the parental body No roch tendency has been detected, while a mechanion is not know, and hardly can be conceived, capable of producing it It hus frequently been urged that mytronmental afecta may be therited cren though it has not been porable to demonstrate this operimentally doco laboratory toto of short durations toe it may be that a proces of thia Idad soon the low of importance during the immensely longer pecade of tomo occupied even by minor evolutionary changes. It bes, on moral occasione been poanted out that rach conclusionfale (sco Heldene, 10014, PP 177-8). Il environmentally induced mutations produce unutarcot characters, or oven i desnategeons, they aro of high frequency it should be poodble to deteot them with a tho couro of ordinary apartments But if those are uncommon, Haun bo abova mathematically that the go to which they give reo ou dot spreed through the population to tho luoo of een very mild degree of wobection. The most that och slowly nating panelor could do would be the production al completely unimportant chercters of Deadly neutral Kurrin nuen. In pito o Jl that by been ald, oma auton is necemuary fn Lorending wat may ppear to be the elects of environment upoa heredity An oumpk of the typo frequently oncountered to medical practice, I make thu dear It is of course below that the children of drunken parents are ·OLIITICI TOL MIDICAL GTUDEXTI more Hkely to boooms aloobolic than to those of the abaternlou, owing to the influence of their bomo life. But art children apocally prone to become drunkards i they belong to a family in which there is a history of alcobolan? Unfortunately woan bo fairly certain that they art, OTC i radoved at once to the carroament o low home. Far to tendency to develop craving for alcohol to certainly in parte bereditary of direct Importance, bowover to the conclusion that it ta borelepunt whether or not one of the parenta hed gren way to rich a tendency before the birth of tho childran This diccion on the nature of beredity can be concluded by returning to tho probleon from which in effect It started, that of matation rato ta manIt was potnted out that thero Aro good ground for mopposing the average buren mutation mtoto bo approximately tho samo u in other animals and la plants, and that crem at its highest it hardly escocde that of tho moro mutablo genas in the Indt Ay Drapopkilla (pp. 62-3) The uniformity of tho mutation-rate in organlaros having greatly kitterent lengths of life is a highly remarkablo pod dgnificant fact. As already mentioned, mutation to pot ratdotad to wy 000 perted in cell activity Consequently It abould be mourirod pa unit of time ita frequenoy por qaration should bo torelovant. Yet the perfectly lapel cxpectation 4 pot fulfNed. Haldane (1035) abowed that if we lako fourteen days and thirty yaan u Irodablo Atal length of a generation to Drowophila und mun respectively the upper level of Iruman mutation of about 1 ln 50,000 (fot the bacmophilla geoc) when adjusted for time is oquinient to e mutation reto of 1 to 40 000 000 per Drosophila federation value to minuto u to fill outodo anything vo know of mutation in that organlım. Judged per genere thom, man has party tho samo mutation nato u Drocopa Tin fodgod per your Drosophila la immensely moro mutablo thu We may well murd at the astonishing relation between the mutation-rate and the generation, Waspective of the karth, revealed by those lucts, yet its explanation Det man.

·TUTATIOX AID ILIEDITY licult to find when we reall that I tabeltanco ba Yeddo Han The great ralos of this system, when compared with any blending mechantem, is the permaDCDOO of its hereditary anite. This enable selection to favour oten minuto adrestages and allom an organtom to make mo of de which arou for sport in timo e in specs, weaping the "whDphoy clect of mtereroding which proved so great a stumbling block to Darwo, on hin unumption of blending (Flahe 10000) Bat this coming advantago of the particulato yetem for wholly dhourdod P mutation bo common. The vital pomenesco of the geva la then lost, oven though they do not contaminate ach other Yith Mendelhen Inbaitance, matatron not only seed Dot, but must not be frequent Selection tatuat restrict the Octure of omtation per medion pofidently to ensure a high degree of permanADOO to the pench Its averige admixeblo limit will be stren frequency pa gentog, to muro which tho troquanoy por time between organisms having lone uod abort lito-oyelos must be rastly different. Thus the human motattoo-catals In secard with the lendelian, and with no other system of heredity while its similarity per generation to that of other organisme demands the fundamental action of election to A manner which must affect proloundly and to diverso way the analye of burpen bacolty Y 115 393 ·CHAPTER TY THE ACTION OF THE GENES TAS PILYIOUS CAAPILLS of this book hero been ro Itacted to dlacuman of the bebeviour of the gee, their kareration and mutation, and of the effects to which they giro Flee. For the purposo particular genes bare betul treated merely u tho inbanted basis of gaven character. It i, however Important to bridge tho gap between gone and character, nod to determine what type of cllects the genes may have and the ways in which they produce then to obtain, in fact, ponao tnformation on the phydology a reaction. Tha wo shall now attempt Phynological genetia imbject which has made great adrnce during the last twenty yan, but its data uro dedved almost excludvely from bon-human fomna trom other colmals and from planta. Yet it as one of direct and practical importance in woen, so that come endavour Drat be made to mdicato a low of its moro important rotalta. At Arst sight toch a tak appear very unpromidng owing to the scarcity of putablo human sumples, but it w facilllated by the very weldo application of tho panoplas or genetic When we find that particular phenomenon occurs is such diveno forms us rodents and insects, dicoty lodorous and monocotyledoboris plents, ther tonuotos evidence for ito auteco In man may be the moro radily accepted. The poverty of the date banng directly upon the phy Qogy of human reactia u doo to three our First, the all amount of attention wbích hur fer been padd to the Pubject gat deal more relevant trformation could be Louloolated even in the parent state of our knowledge, Secondly the fact that much of much data mmt be desired from operiment, and this la retrated to the most mount luita in man. Thirdly doce man belong to the Hamur hoia member of a group protected yaing to clecte of the 74 ·To TAZ ACTIOX OT TAB GET arroament to an atrordinary degree. Compared with thomafurity of animals and plants, the pool lity of coniby the action of the gena in diffamt coodtrom Ls lo that dan reduced to a minimum 'Yo may tbordare attempt to Hody the effects of the gener, ud their interaction with the cartranspent m the widest senre, having at the outset rooog. nbrod the past handlar decearly impoved upon pchen to quiry LTH ITTICD OF THE IT Catain types of actio eloct may actuly be dumited bolore attempting to consider the behaviour of tho gena in vartod anytruments. It will then bo poodble to give a bod Locount of the dominanco phenomena, and of a fow Instances ta which genetic retion has been unalyzed from the phydo logloul point of view Attention has already been directed to the fact that dis Hoct genes may bari Darły or completely identical effecta. Thus retroutie plementou (p. 47) may rerult from the opera too of fire, or more, diferent gener. Of theso at least two are autonomal, ono being dornment and tho other rccentivo lo expresslom, one la receastro and totally si linked, whilo two, ono dominant and ono recoudre, are partially ki linkod and probably allelomorpha Only the autosomal recedin I datingmahabile in its cllects anos, unliko the othen, it producen denfo.co.in addition to the chancteristio change in tbo cye. A munber of dimilar tratando might bo diven, och u kontoda follievlerta (Dader's Dreno)which has been produced by • -lnkod pone, though the disorder is Duudly inherited u un autonoma dominant. However tt pas profitable to reduplicate anunla are in special circumstances. Duttoct genes may also produce effects which are ray dmilar in Hod but diantat in degree, thou rekenwilng tho modo character to which mulupio Jelomorphus Tento (p. 80). Attention has already been directod to the three forms of cpudormelyi bulon (Chapter II), which en chanctuated a mild, dystrophis, and cover dystrophile Yet there are not the rerult a Nelomorphs but aro doo to ·70 OLHETIC TOI MEDICAL STUDENTI three gena at least one of which is known to occupy a dotnet Locus. The first two aro utosomal dominants that producing the dystrophlo foton bang rather foregular in aprendon, while the third, responsible for the sovere dystrophio condition, is rocettivo add partially for Unked (p. 50) The instance to far given of genes baring dmilar elects relato to nro abnormalities, and I know of no occudona on which they have been brought together in the Ame individual Were thy to occur reteral detect powillibas aus, but only two of them require conddata at this stage that to to my the ropulta might or right not be cutaulettre. Num.cou mstances are known in animals and plants in which character duo to tho operation of gera havo been combmod, rometimes without increang thar effect. The tho Tor' rabbit one in which the stuff guard-hair' sro greatly reduced, procluang plush-H coat of cammaca value. The character recevo and it may be due to the action of any one of three stres, two bang linked and no curried in different chromosome. Their dilect tho amo wbether one, two, or three of the hobotyros recendres ure present. I am not acquainted with any definito complo of tho une typo in man, though doubt lan uch odst Horo atten, gene producing dmilar characters are additiro in their action. This is undoubtedly vary froquent in tan, particulady in respect of quantitativo difference. An cxcellent cumplois provided by human bortit. It can be demonstrated by means of correlation (p. 07) that thibb partly bereditary But manriages between tull and xbort perents give rise to bo dercut wgropattoo, owng to the fact that bezght to controlled by many genes productos mall cumulatare citecte Yhen i character determfood in thla ny brodia in tboke animal or plant in whlob . larre progeny au bo rart, it be found that the mofodty olibo attupring approumate to the average height while the par atramo farms bocomo progressively are tho propor top bearing definite relation to ono other auch that the ·TIL AOTION OF THJ QIXI bolo poup foto within « are of normal distribution This appllos not only to the P1 bat ubao to the generation, in which the curto remains un model that is to my It gtre no folation of regregation into different durch Soch , woodltion i Inown a wootnuo natoa It but not be suppo cd, borover that the Inbalance involved to non Vendelan. Indeed the analysis of beredity andertaken in the latter part of Chapto III can admit DO mch vhow That It is determined by tho particolato mechanlom is demonstrated by the fact that in there arcumstances the generation la moro nilable than the F1 (p. 00): the inbentanoo being mouldisstorral It ta plain that wo here bero the Octurono al gesso inter action, to the real thet a number o geres, operating quantitativdy are required to prodoce given toct. The infoence of 000 gede therdore depends upon the preacto of other. But puch Interaction may tako darent formt, well-known virtant of it being provided by the moduring factors. Thero ure genes which onert no known toftuanco by themselves, so that their critenco an be detected only to the presence of others whore ellcata they modify Such modifying factan bero been studied to creat detail in otho pechon of animals and in plants, and doubtien thoy arou important to man udkwhere. Indeed roaul todicabloom other activity are common la human genetlem. It loquito froquently found that • gtvengono prodooes nomowhat distinct rerulta in diicrent indivdu. Alinlon, for cumplo, binbalted us simple recordve, but the may depart from the autreme, and typical, form with white hair and pink eyes, Somo buto palo bluo ora and pale yellowlab hat Il auch mab-dindons of u type uppar sporadically tho variations may be environmental (PP, 00-05 L, an tho other hand, they aro characteristto al particular familien, often to albinion, they are attobutable to modifying factors De bedshaped corn that the database, the best 4 mod the cuber of looks at way potetsbeybeheer og thao kutwory from me then be bram of the bone then be patty proportion tor ·T8 GENETICI TOL MEDICAL TUDIXTI There may be detected only by their effect on the mala geno. In albaniem it la probable that woms at least of ruch penas oro ther moditymg action to the fact that ppment production tends towurde colour-Atuntion, to that pale factividuale ero moto venditive than dut to u nal DURO in the total umount of pigment. Often, borover no much duplo interpretation is poolble, and one geno way act caly in tho tostion provided by tho Lotivity of anotho Thus the symptoos of epilois ero very variable, and Gantha and Penroso (1993) Ahowed that this is in part due to the operation of modifying factors which affect tho espre non of tho singlo geno rarponible for tho diwarder This by urally dancrībod m. dominant though it appear to bo Loom ooly trom tta beterotypou effcot. Simllarty Popen.oo und Bruunucho (1961) obtained cridence that moduying factors atlect tho mapllantation of Friedreich, Atans, though the condition unilactodel and reocare A logoul exterior of the conoept of genototermotion en bru.com an exceedingly important group of phenomena constantly encountered in the genetics of animals and planta that is to my two grues, cuch responsible for definita characters, muy combfidio to product new elocts of a dialnet type, not merely the averago or the sum of those to which they give rise independently It lo lar thus round that apeder hyboldu uro frequently found to pomic chancters abuent from both of the parental forms. Wo may tako u 10 complo the tradt fly Drosophila denogaster which normally powded rod cycl. Brown and scarlet cye-colour uro both recensive and due to the opention of entirely distinct gener Yet when there are brought together in the boonozygord state in the same animal, they interact to produce whito o similar in eppanuco to thout doc to the operation of Tokod roce tra dutinct from other of them. The combined dioct of different genes hu w for surely been stodied to man. Howeva tbe modt onlycal natuto the type of pbergtochon bere discovod, whileh has been demonstrated In tho mox direit forme, laro no room for doubt that barch for it would prose suocatul ·TH" ACTION OF THE GIRL) 70 Attention must now be dnm to an exceedingly tuoda Toental propety of genetic actions that dnglo genes in rapomabus for multiplo aleets. Several omple of this bere ahady been given incidentally but tho cubject b 000 which mats qocal coorderation Genetests, whetha they Hudy human material or not, uro mually concerned in follow In the egregation of particular gene. For this purpore it la convenient to select some obrio fature which were to mark the presence of each procedure which tends to obecure the multiplo maturo openlo action. So much mo, that the mistake is sometimes made of regarding ach remo u tho baltablo prenor al ono particular character No vhow could be more tale. We wil at prosent resteet our melves to dloudng that upect of It which wrongly Loodata unit ends with dnglo character Quito poucibly careful namination rould reveal that all De produce multiplo eflecta, aften of urbaingly divorno Hnde Eren with our present limited bowledge of buroan fonether, the Instance in which there have been detected to men and very numerons, and a few only will witoe u samples. A Anglo gene, denudbed us dominant rospongihlo both for broo-tragihty and tho production of blue clarothers while « dnglo reocmivo gros nito to tho Laurence-Mooo-Biedl ryndrome, tho foature of which are palydactyly retinal degeneration, mental dellokondy obouſty and bypogenitellan. It has already been mettooed that the form of retinit's pigmentos doo to . sutonoma recendvo to wocated with deafnom, in addition to tho migation of pigment into the rotias (p. 16) It is an important fact that para may influence the general constatation to a degreo quito out of proportion to thar who dilects, and in a manner wbolly unrelated to them. Por temple, albinos ure, on the areas aborto in stature and lou bardy than an damaly pépinented person. The prevede of the gene responsible for spillola b moct arty recogated by the abanscteristio distobution of the scenoms Rebeccum on the loc, apeckely along tho duro-Llul folds to which It gira de But thl vymptom boun do obrow ·0 QEXETICI TOL KEDICAL STUDEXTS relation to the mental defidesay and production d Dodules of pouroglul overgrowth in the brain, which make the progom of this condban o gloomy Simlerły naadly all of the genes which havo win by mutation during the contre of geneto aperiments are dbandyantegrown to thetr effects, though the obserable characters to which they are duo are often quito trivial. Ln Drucophila, for aumpk, auch Des umuully reduce tho length of life, and the number of lud po day by the females yet wo may recognise them by the abecco of bustle on the thor or by a berely detectable change in cge-colour Nevertheless, that elect og vlability makes it clear that Asch genos produce other and moro profound changes of a phydological idad. Too shoort utresul nature of ach altations for tho general vitulty of tho organlam umores w that tho Lotion of Anglo gend must In general bo multiple Tbo tacts mo for decribed lead to & concludan mach Cooroqucnoc. Genos giro rio to multiplo afects, and they interact with one another to produce the characters for which they are respondble. Therefore, they must combine to form . balanced system, or be comples, constituting a form of Internal environment within which auch gede minst ect. That h to my it is not pomible to alter wy onglo gero by rocoor Hoatlon or mutation) without influencing tho operation of many othen. Similady the directs of a gtren rode will bo changed when it be placed in a gese-comple whose comport tion de couddanbly trams that to which it ascenstomach This situation is, of course, attained when a marthago COCO between recte which rely interbreed, so that I diicreat genetio stotion bas been built up within ach. The elect will ordently be grate the wider the couch that wo study thou between rhoch, person, and genera producing progtest frely Doteworthy reelts. The degree to which wo con gumine the activity of particular goue in different pend compleses bowerp watctly limited Obspring an only w from moetinge betrece fairly dosely related rent, od these must havo the great bulk of their pare in common Purther in wide outcome the hybudda uro teully stele, ·TAL ACTION OJ TOI QIX35 81 and in the auch eill tomand in a renc-ccples to hull of which it has been adjusted Nono the lear, tho oblccts to which a given reno may pro re when placed to DCW etting may bo dielmler enough from those which m Dormally attulbute to it Wo may tako u dgnificant ramplo from the genetics of fish In the lataan Top-mindow (Platypovouw) doglo rex-Hinked geno 8p merely produce dominant black potting. The hybrids between this and the Stordal, member of another fon (Xiphophorus), are quite healthy unless they receive the gedo Sp from their Platypoch purent, which in the bybodd gano compla pro Ho to obtal ouncervas growth (Koure 10105 Lod)). The form of mankind purviving to-day belong to u ogle pecia only nor do tho vanou human racos dior - cently to product any detectable degree of sterillity or el aknormality on inter-crong and there in the first recognizablo dgns of those dierencol whloh lead to tho cvolution of nuca Into distinct speciet Coprequently the amount of modinoutoa of the renic-complex which one trany nadal crowing in man is mal ocurrpared with that which can bo withoud in vldo out-crowd nga in other mal and plantı. Yet wo may bo confident that further stody of human geoeties will abow deurly mough the tafluence upon tho alect or partioular rones which results from the cotton fo DOWhat distinct de complexa No ero instances of the und unknown today Too woolly hats of tho De TO bebera * domimnt' to the non-woolly typo, but ito beterosypoca amprodon is subject to comelderable variation to proces with Europeudt Otto Hot (1001) analysed on Instance in which the fetu (oc, les probably ove producing dollar ropulta) promo by natation in a poro Norvegles stock Hoo the beterosyrotes were very constant. The difference in modidabilty to the elect of the godo may very roonably bu attilbuted to the greater variability of the peo-outplex Long tho otpring of Intandel comes then an almo [rom menduga within the amo not Numatow tostances cait to the records a apartmental Cenetlos in which areas, ter string or cocte to.

·52 GEXETICI YOR ULQICAL ITUDEXT: genc-complex to which it is unsocutomed, has been restored to that from which it came (Ford 10100). In there aroumon #tance, it ha produced one more the chance for which it Dormally raipouable. That i to uy rich an ultenbon in dieet is dus not to a chango in the geno itzell but to change to the response of the organim to that gene, consequent upon recombination in the set of genetic factors with which It has to co-operute. A well known instause of the fact that the gates produce dilatat eflecta in different internal environments in provided bry tax-controlled inheritance ? Thu kau condition in which the Acton of a gemo u only (or more frequently) detectable in the cnvironment provided by one of tho kin It I cannully to bo distinguished from sou-linked Inheritance (P 09) la which the relation between genetics uod sex is of a mechanical kind, omogena being carried in the m-chromosomes, which are reponable for xx-determination Sex-controlled genes may be carried in any chromecanic and when, was unl they are autowomal, they are trunknitted equally by either c. Their relation to res I therefore physiological ona Kedy totally kx-controlled pena de known in kwa animal. These gire ordinary wyregatlon button one or only though showing autosomal transmission la both, Daminant wbito-larclock prorida & burran Instance, in which the character luted to tho mala, wo door prematuro boeted Det (p 100) (Cockayne 3030). incompleto ex-bootrok in frequent in Wan A form of allgophrenia, and tho Laures.com lloon Bredl syndrome arc ach nipple unto al cocorisch but they are cotrober in mala than in female because tho gere determuning them do not always produce ther effect in the environment prorded by the female sex (Calk and llather 1030) Oligophorenia Odcint about twice n allen In males u in females, while in the Laurence Voor-Dheel syndrote the di cresco to rutier lent. It aboak al be observed that the koondary and secesary characters wbove dovelopment must be genetically determined, provide Tak kto wide-anted tekerlek but that tona hould be taken 100 uy soat va mz-Dalur ·TIL ACTIOX OY TIL DINES 88 cumpla ori-controlled fnbaitance, for they appear only in coc of the two mora II. DOKONAXC KODICATION It will now bo clour that the cliccts of a gooo aan be varied by change in the rat of the beredity matadal mod, con roquently that they are ansceptiblo of selection Indeed the concludon that selection aun modify tho action of a gene, while the gene trell rematas unchanged, bano of the bigbert Erolutionary connequence. If the characters produced by . BED 250 advantageons, they can bo improved, it du advantageous, they can be minimized. Such effects hant now repeatedly been obtained expedimentally (p. 80). Odo of the most valuable aspects of the mechanban is that which relata to the evolution of dominance. The pood bllite arting from the selectivo mobilation of the effects of De were first fully yppreciated by R. A. Fiher and it to to hla brillant analymo them that the concept of dorotanco modlication ba duo (Fbber 1938, 1031) This mbject must ont be studied Lartefly from general point of viow when its bearing upon the problems of human genetbean botadionted. Tho effects of raro genes are almost wholy limited to the heterosypou phare This ta Indood obvloos, Ance the chance of beinging together two turo boterozygoton, from which gourenco abono s homoay goto can crise, dost bo remoto (the actual proportions will bo ducimod on pp. 180-1). Dandrutereous genes are constantly Rubject to counter polection, so that they moet borre, judged by their frequency to the population at wy opo time Novathelons, the organken muut here a wide pot aperience of them doo, u alroudy arplained to Chopta II, mutation is a rourent pbanoacaon. Therefore, umla Rich gerne er lethal that their bearen laro do descendants, animals and planta bare nowo opportunity of modifying their response to them by adjustment of the gense-coupler Suche proo l be to the direction of mitigating the toiluence of dimdrutageow tend -ben to the betodypu Hata uy similar adjort meot to respect of the bomosypoto will be relatively minoto, ·dxxITICI TOR XIDICAL STUDEXTI owing to its immensely greater runty Therefore there will be a coolant tendency for reloctia to bolify the clients of dEudypta tous geras in the direction of puppresung them in the heterozygote that is to my to make them recadro. The content tenclency wil, of course, operato upon the elects at an advantageous peona Thiene El bo magnified in the beterozygoto vo that they will becomes dominant ta arprention. Purtbezusore, the frequency of such a gero wa locrou, o porting mort material on which pelection cu act. Consequently the proces w bo far swifter than the drift towards receivencu of disadvantageous character, whilch depend for their maintenance upon recurrent mutation. It la plain then that . Dew advantageous geno will spread through the population, while ita ellocts will acqur domat nance That is to ay it will diapouka i Lorner wild-type allclomorph, which will become a raro recaptve. Yet the pread of an advantappous rene sometime Arrested during its course. The count when the character bo which It gtros rito reach en optimaassa finquency in the population owlay to . balance of mective agendah The resulting situataon ua of great practical importance la medical gauctoritas It will form the subjeet of the text chapter When a character is no disadvantagear that the Indick du pasomog It contribute little or nothing to posterity it & apparent that no opportunity far caminance modifica Una arise. Lo there marcumstances, the angel noodlton should be preserved, and wo may expect this to be such that two doses of gene produce a greater elect the one. It be found, Indeed, that moderately disadvantageous genos * recentre. Yet I can of genes abo exista rcpoon bho for atrewly diadrantegrante altecto when belediyebut wbīlo the cowponding homorypote, 4 sbtainata, product even more XXL results « that, in many instances, they do not purrint. There are obviously the group is hicks daralance meditation kas never takes place. Nor has it to respect of the nine member of a multiple abekomorpha karton for there will barily era be brought together and in paimental work draged to that excl. Vc nou ·TO ACTION OF THI GANCS 88 therears that the beterosygotes between any two tard membe a tho kila ura intermediate, wbile tbove between ach them and tho normal alleloxoph are not Those facts throw much Hght on gootio action in men. Hany otho ture disordoo uro trao recedra It bo poteworthy bowever that this stato bas not been pafectly attatood to romo of the more dangtrop of them, rodoma pipmentorum for camplo (p.) On the other hand. Large ntuber o cooditions, meno di velou Hod, ure dancribed u dominante's epilole and Huntingtoo . Chorus may be dited from among them. Yet I have pointed out that this lo upotptom tn nearty overy instance, once the corro ponding homosypotes baro rarely been studied. Tho theoretical condiderutions fort outHned uprost that the beterosyra effects of auch genes will wally bo koncwhat intermediato. Somo orience for this condorion can bo obtamod in more than one way First, very few instances Are recorded in which the bomorygotas muy actually havo been obeer ved, and they appear nully to produce the known carnet of the coodition to a highly reported fortu. Inner Roberto (1940) daw attention to podlgren of foon of dominant brachydactyly in which tho only almormalty condata in abortening the middlo phalanges of the indes Anges and toon. An alloctod tadividual, being us www.boterorygota, marnod ble fint courin, the daughter of an attooted man. She had probably been affected, though bo ww dead when the family history wu compiled and tho potat could not be established. The couple had two children. The elder nu lected to the eme degree us other member of tho family od proved to be a heterototo (banne 000 boormal and to normal children) Tho younger child, boruter u promly aboormal. She bad do ingou a tool und ber 'Wholo scopi system wus in duorder She died within a you being mahlo to dovelop. She wu probably a homosyroth such . conditio u tht aanpot bo ranked us dominant at all Purtbar cridence that dangerous dhabilito un nrly trus dominants bouppted by the parlebilty of their 7 ·88 GEXETICI TOR MEDICAL ATUDEXTA beterotypowserprebon Tho is notable in both the instanca just dted, spills and Huntington , Cborte Thato e lodead a general indenny for the exprank of gather to be mort notable when beictos you than when homo SYPOUL Pruner Robert (1950) has stremend that recentro conditions lo man u0 se constant than ero beloonygon over. Ladeed I have myself found, to the course of esparta mot an artificial dominance modifier on, that the beter Typoter product o greater resim ol rankity and are more modiflablo bry mlection, tbud ano ather of the bomo Xypotem whic of these, the sormal is more content than the mutant (Ford, 1940). The reasons for this can be statod briofty There will often be crcumstances Amiting the ponudbo rango al protection of a post. For matapos, for ctning amawats of a pigtreat tend towards maturitiota la their effect, while the site of an orpus etuoot fodeialtely bo loorcared. This abould make the strect of the page donc condition to mwepuble to attraconis fail.com whether of changes in the gene complex or ol the external environment, than that doo to the action of the two alldo zapbill. Further the Lormal wielomants will bara bera adjusted to produce the most favourable, and thereford rather constant, effects within the range of the internal and eternal vironment to which it is pecully exposed. The degree to which the edtects of sgeno aro variabile to called it arutaustoity It is this quality with wtulak we doel for lutande, ta diatusing the fact that the gende producing dozalaunt polydactyly i razponible for characters ranging from well-developed antra digits ou both bands and left to a bw-formed knob in addition to ti so naraAngers of peste haps a single hans. Expresuarity relates to the degree which the characters prodaval og god are expected On the other band, the frequency with which gene produce any attedt at nulla alled to predraro Hount of the rest to lur dianad Eurocoupleto pestetrance; they are always respotoalbiler for Kitas cflect. Doorskonally borerer react with beterosy To manitation fail to prodaco vay detectable characters the ·TII ACTIOX OS TRE GLAS penetra b Incomplete. For instance, diabetes toupido mually dos to englo gerorth beter rygous sprendon, . valle dominant (17) This occadonally tail to cause the discedes, which the loro ekipe geleration, though it bould be truonnitted regulaty from parent to offspring Helloal practitioners met be apocally cautions in advlong ther patients on the probably of trenumiting roach genet. With beterozygous apprenton und full pornetrines, una lected todiskoall cannot have stracted children: but when peno trucos incomplete, octarlonal aceptions will occur Should the penetrance of gero bo shght, the condition to which it gtros rio vill appear sporadically in ocrtain familles In these circumstances, extracows agences will often tend to Toke It There to some evidence that diabetes mellitus I due to a good with beterozygous caprendon and about 10 per cent of penetrance. It has already been pointed out that the effects of bomo Troten aro mually las mulablo then an those of betatyrolerIndeed, Laihores lo penetanco do pot room to bo countered very often la receres It la poble that the Lawrence-lloon Biedl godroms, a recondo conction doo to englo gene, la pot anar aproved that be to my tho povetrance of the ro is not quite completo It b, bowcra doar that the dominance relationships of tobated charcters in men ato datinctly shoormal Nor this to bo vondered ut conadering that they aro pro duced by relaction for the conditions human rodety doring at laust the last two hundred petenbos baro do pated widely from those of a wild spectes. They havo in Loret been unique, but they bent womewhat resembled the station to which domesticated form uto mbjeet Eren fo. primitivo human society Individual must have been Tilbod for and protoctod by quallbot other than bodily adaptations to their environment Indeed from an ady period in the evolution of Man, Individuele vbo would bard beo dunated from the populations u breedhar-unite durtag the pro buman start must have made coordable contribution to postelty Such . Deretios, o in roma ·GENETICS TOR YIDICAL STUDEXTI lostanod. rorezul, o relation will not only all to prodoco tho Dormal colectivo modification leading to dominance, but may break down dompesce relationships previously attained. It is in domaticated species that we and the greatest abnormalitios in dominance adjustment « leblo dominant black form ocown to the gulpa pe while the horales condition to ottho is nearly dominant abro. Spoclos wbom do nestation has been of an unnual kind uro those Whors dominanco adjustment le partionlarly abnormal Indeed the peculiarities of domestis poultry in the rapport which at itt appeared mero otceptions to Pinher's theory a dominance, have provided by their very firegularitas daar proof of its operation (Fisher 1985 1988). So too Van, wbomo oporuro to electron must ovidently bo erceptional both in degreo and in kad, applies cramples to unoul number of a ruro coodition, that af geros producing hetero vrou electa which must bo deleterioad, but to . allgbt extent only It has already been explained that this with Hon Dot normally to bo unticipated. Instances are pro vided by phalangtal sypostosa, piebeld spotting cangooltal cataruct, and other R. A Fisher wu the first to rugret that dominadan bo ptoduced by selection (1918), and be concluded that the gporntas upon the reso complex in the manner already described Haldado (1000) mbrequently proposed alternative method of dominanco modification. To polota out that genes probably act by producing eynich, and that there will opento eflectirely only up to a maturatioo lovely abovo which further enzymo production will product DO detectable ellect. It bus roady been pointed out that moltiplo alclomorphe control stren set of characters quantitatively Nor Luming that . multiplo alebo morph redes cists at ach locus, Teldana pototed out that dominanco modification might ato by reco tom of dierent allelomorphlo geben in the following my Wamey Rappose that the bomosyrote te dwo to the operation of unnecently bigb member of the price, stoor selection will favour thoto allelomorphs wboke activity ·THE ACTIOX OT TIT SEXII b aident to rabe earymo production to the stuntiam bd even in toglo dove. Rare reall alwayı bo jodged by the reaction u heterozygotes, und thow Ill be firoured which oron to that pho do not lower consume production below the normal mutunton love, buto oroko m Impe fect development of the charactan camcorded. That bo to ay Fuldano enrouegos dominance oriung through a chanzo in the gene ftuell, through selection of 000 ntbe than of Rotha member of a multiple alleomorpha It may bowerer be questioned bow far maluple Jelo morphs are arulable for this purpose at each locus. Further more, the lovel of the threshold rate up to which onensyme acta will bo detarmined by the general constitution of the orpanlom and m, in part, by other react, thus it boot ceptible of modification by election operating on the gene cotnplex tn the manner proposed by Fisher It should also bo noticed that ceperimental proof a Flaber's method of dommenco mollication has now been obtained in a number of instances. It has indeed been poseblo under apaimental conditions to select the beretouygou aprendon of the characters produced by a given rono until they here becomo pourly dominant in one lloc und Dourly reeen in the other In these circumstances, it has been establlebed, by arooring with the Dogmaal forta, that the gene Itxell has recomed altered (ha, 1930, 1938, Ford, 1940) It has been strewed that the genes of an ormantem not together to form a gente complex adjusted by selection to retarouble rorult. Tbo chances therefoto oro arcodtogly remote that purely random changes in the gener, roch urte by matatiog, hal mo fit in with the balanced rytom already in erstence is to promote harmonious working The probability blodeod almost over beloning that the elect a mutations will be disadvantageous, circumstance to which attentioa huu alizedy boon directed. The conddern Hon that mutation be recurrent phenomenon elo contoh batas to the real was argentina livtag in a coortant cotirouvet It would rem almost freredible that mutation bayiag advantageou electa sbould era now we all that ·OtXITIOS YOL XIDICAL #TODEXTI lostadog i roronel, of docthan will not only call to produce the bone) wlettre modulation leading to dominant, bat may break down domaroc relationship previously stalood. It li to domesticated speciy that we and the prontest absormalto in dormance adjuatment vlado dominant black forma mais so the guinar pe while the boralen condition in atto bas Daunty dominant alm. Spodo whom dovestation has been of an unusual kind uro than whoud danirano jua maent is perticularly abnormal Indeed the peculiarttia of damjesto poultry in this reports which at erat appeared were exception to Fishes theory a daralmanos bus ve gerided by the very irregularition clear prool of its operation (Fiber 1888, 1838So too laz whomo campoort to selection nuut evidently be aceptional both ta degree and la klad, supplies cataples for workoal bambers of toro soudlisons that opensos productag hetero wyroon diecta which manat bo docterious, but to light extent only It has already been explained that this wilus son but normally to be ablepatet. Instance at vided by phalangeal nydobos, piebald spottio congendal tarach, wood other RA Haber was the art to worest that clarinasco be produced by Kolostsoo (1928), and be concluded that this Operata upon the geto-compla in the manner already described Haklans (1990) Fabboqueatly propored alternatya method of dominace modilatoa. Lic pointed out that gene probably act by produdng wory, and that theme will operato allcctirely only up to a maturations leven abort which habe enxymo production will produce detootabla doct. It bus wready been polated out that multplo allelombarpo control gren set of character quantuurely Now kaming that a muldpla wiekos normal niet echt st uch beim Huldava polated out that dominance modibertson might ses bry socken son of Litterent allelomorphlo and is the following may We pay mupport that the boraygoto be due to the opartion of uncocardy higt member of the water And selected farow thouo aliciamorphs whose activity ·THI ACTION OF THE GIRLS 01 pheyl-thboura ere phenotypically similar for this character but If their consultation ba TT od 17 respectively they are renotypically dierent. On the other hand, two individuals may be genotypically smiler bat phenotyplouly different Omg to tho operation of environmental Yeration, and it is this phenomenon which we must now briefly study The environment , in Jl Orrantamsu important u beredity in producto the chances of the individual bat, already potated out (pp. 745), avironmental parlattor a particularly dibcult to crumbno in the Mammal, doce they are protected against it to a high degree. Tbo reason for mach protection ba Dot dificult to find Every organlım must bare en optimum environment, one which sults It bent Obvlowly it is to tho advantage of all individual to livo u nour to their optimum conditions u poodblo. This they may do by migration, by adjusting their habits and cooloo to changing conditions, or by manufacturing u tu u they aan as cavironment of their own which they carry with them and to which they permanently Hve. This latter tochniquo has been perfected by the Mammalls in a remarkablo way La lower forms it b pondble to study the bodly effects of altering the more obvious compooents of the envtromcat Rich w temperaturo und humidity Yet the thermostutto regulation of the Hummalle tarch that . departure of even faw degrees from their optimum temperature, which they themselve maintain, la data to tbera. Similarly changes in bumidity can have but limited ellect upon them, while the conftitutioa of their body-fulds is regulated with great auctitude. It le plain then that Mammals üro in as a tremely constant environment, one which wpproximaton to their optumom, mo that thoy are only aubject to coolroa mental vurution to a very small atent We are provided to bre form with innumerablo comples of the fact that the para produce diareat effects in different tvirooments, that there Httlo chance of falling Into the fallacy of repending them the Inbetood bude of particolar character, In Tammals, when tho umoont of cavtroa mental vulation no much les, this mistake moro ·OLXZTICS YOA KIDICAL STUDEXT: rcadlly made. It cea carily be shown in the majority of organ Imma that changes in temperature, in humidity or in other cements of the external environment, will modify the action of the genietYet there are instanca la which auch efects a be detected within the mall environmental range which the Mammal ca experience. This is true eren for 4 poodition controlled - Lacurately temperature. The point & efficimtly strikaag to melt borse donctiption The Himalayan rabati whito form with blackish extremities. It is inherited us simple toere, being uc to the operation of genrech which is a member of the abno Kia of nalupke allelomorphs (pp. 80-2), Himalyan rabbilta 070 bora wholly whats, ince the geoo is and which proventa pigment formaaton at the mammalan constant temperature A few degrees lower however its action is quite different and leads to pielanin production Correquently the extremitet darken, for thoy lo bent maro raphally then the rest of the body and fall to attaio the tree body temperature. The the exposed parts, the up of the same, erat, tall, and the fedt azo blecloth in adult Himalayan nabbits It an be ubown operimentally that the Himalayan character la not duo to the operation om geno costrolling putters, but to one which produce different tects at different temperaturat Il a arte on the back of Himalayan rubbita be shared the halr which groms again will be whito It the animal bo kept warm and black of it has been kept la very cold conditions Several other mere interacting with temperaturo lo admilar way have been studied in the Vammalia. Eamples are provided by those respondble for two of the thrpo chinchilla phases in the table and for the Slaces to No asb striking environmental dieet bare *o Lar been detected io Blas, asid our knowledge of environmental variatsoo lo burned geactia t wall It rzust be bought ther In Icon obylou direction. One of there is the elect of maternal se upon the penetract at by the oilspring it la tbought that a number of conditboorte were do them la pest genetis, era extied with peater frequency in children muturralage edredos do Instanek free porced ·TOE ACTION OF THE QEXES 03 a theke is mongolian filiocy (Pearos, 1989). This is toy wodou condig, often coming death. It be believed to bo Inbelted, powcibly it b. dorotnant with tocompleto pero trunce. Howed this bo pot certain, for the occurrence of ertroumental redation Introdoces pecial difficulties into tbo repetio malyalı Erumples of the phenomena now under discudon sro aldently provided by thoro genes whore known dioct is limited to increasing the susceptibility or patient to footion or to other condition. Then aan bo do doubt that the Bability to develop ander is inherited. Haldane (1080) show that the chances de cancer appeaing in an indiridal sro Tay much greater if one of his parents bus buttered from tho dneuse than they are among tho member of a comparablo ndoa memple of the population. It be undoubtedly true that no of the child isent in tho production of cances Lone continued timtation et a polot But the probability that och fortation de Indtato & CADOU changots groter in some constitutoos than in other and it is this tendency which h, et laust fa part, Inhented. One of the mout bating features d cancer is the multiplicity of its farm. It la pomible, Indeed, that some of these may bo voy mlar in most respecte produced perhaps by differat odthagencia acting la distinct genetio Ituation. This may well bo true of the carcinomata and the wroorata It is cury to break down in adjustment, and to a variety ol waythough it may be hard to buld it up. Concenably I cel may dell'arentiato through many unch Dar aan romadla mntation be diminated from ubong them. Wero ener loftlated by one specito mutant change the low bove of brutatioa-nate would reduce the actor to Dearly degtighio proporthoog boto number of dhatinct matation may well oroke . ancer Bren, I am not tocined to attolbute much Importance to mutation in the production of ancor Od of 30 who has bedded do, 14 e deri pod thet e puedes emple of 05.20od bonds Pathop of the 400 peta y tregory, the bow proup ble da do te wanted to buon ·94 OIXITICI TOL MEDICAL STUDENTS Casard sometime to countered in which , melanotka tumour gira doo to secondary growth one or more of which uro wpigmented. There Ruggest lodependent motations It much more probable, however that they hare grond u metastases from the original dte. If they represent cartroomental modlications, the sponth taking dullerent formu to different parts of the body Indeed the bereditary tendenoy in ounce to womewhat opposed to the bypothed that omatis mutation to al aume of the direure Though gena certainly waist which ruso the mutatloofate, it is unlikely that they would account for a hereditary alloot of the observed magnitude Tho genetle components in the control of cancer muy well bo complex and variou. The nature in quito uobows, tbough there can be no doubt of thet aduenoo Tbe diversity of the disons in lan nurm us that this may bo Tet greater between different group of organitms, so that Attempta to deduce the reactics of human canoer from breedlog upcrlmente in solmals should be made with extremo caution. The influence of the eartroninent la oroldng the clocks of na 1 apparent in number of other decucu. As a wel mowe, rickets is due to deficiency of vitamin D. The may unto trom in inaliency of thomo articla of dhet containing It, much us fotot, r, butter Is, and choche, or under-aspoturt to runshine for ultra violet light leads to the production of vitamin D in the uda Crom pro-nitamins auch u atostorok The discute is coordon among children of the poor clepas brought up in the em les conditions of bu dtiet. But it and to moch moto ausly in mome comtituttoos then to others that belors the ducovery of vitamins it wu desdied simply u un inherited delect among Hum populations a pored to wo eppureuy similar carlroomeat, it occur frequently to sono familia but not at all la others, while children who develop riekets may have bealthy brothers or batern though there may be po obrlow difference in the upbeloging. There is a fact Laisty Hvoor evidence that, in como cures at least onceptianity ·TAZ ACTIOX OT I QENI. 05 to the conction due to the Lotion of . in.glo geno with heterozygous prendoa. When both vitamin D and allency Amabloo ure lacking this would ensure the inhottence o bickets upon amplo Henddian lines, though the creation of the gezo vould be completely obecured in family supplied with a well balanced dict. This is caurly 1 pulla tuation to that described in Chapte L, in which the prodoction of yellow fat in rabbits is ont-factorial and roceedino, giving rise to strict Hendellen vgregation but coly in animals applied with green food. Without the utide o diet, the presence of the rese is todetoctablo The allergia ure due to rarios environmental etail Operating in the presence of . anglo geng, ually descubed - un utosomal dominant Horover Wiene dal (1980) buvo demonstrated that it produces allery doveloping before puberty when homotygous, and allergy developing after pabaty o elo normal carrier when heterozygou. It partially ka-controlled, tooo about twice u meny mala u fomalo uro alleated; tho kaul dilaman propumably being restricted to the beterveyroten. Allerplo discuso may mo bumerous format: Infantils conne, Banter prurigo, lichen utiontoa, urticario, light or cold-wondHood dn, food alergy wethma, hay fever, migratoc, and others including angioneurotie oedeme, at which distinot non allerglo form cho casuten inbertod us amplo dominant Sometoch, bowever stren form of allergy is inherited to a family or 10 mall proap within a family to which various types "ppeur Actually . Anglo gene la responsible for an, but other genas determine which there in particularly liable to become rondtiped in its preko Auglready mentioned, Receptibility to lofacto con los often inhented (wcaelo R. 184). Gribabcrg (1901) www.cl that * single gode with boterosyroos aprowlon la mpumble for Inflammatory coodition of the ecocuory nawal The penetrance of the reacts tocomplete wine link depende upon arpowuro to tnfaction. It can often la lata trenerul ta that xoc costitutions are more H+H49 Infection than others, though the genetic poate fi ·DO GEXITICO TOZ NIDICAL STUDEXTI may be entirely mimom. Doubtless it foot often bo muit-factorial when twins are born of a typhllide toother lastano ato known to which one only has contracted the dukces, though ther opportunitio lo mlection must bare been oqual and great. Such a ditamo u tha muut aircost certainly be sectic Tho perctlo nitaeneo fu infectious disease of course more difficult to 10 mth anoding age, dact tho bazed tary constatation become one only out of many agenta predupoong to immunity or the reyem 120 mettiau? batory of cach todistdon and his past and presenthalts of ule, lo addition to his genetic outfit, are od great and obvious importarse in determining twistance to infoction I ILIC MEYWOLOGY IN KAX The methods by which gena produce the characters for which they are respongblo laro been studied fa mocb detai In lower formu (Goldachuidt, 1938). Very little Information on the subject & solar srailable la da. Norert clean, It would well repay carchil bavestigation, althougb certain upects of it requiring operimental analysis and reporting preto to human material It has been established (Ford and Huxley 1017) that De control mter ol proctures in the body and the these and tbetr oort. There and be no doubt of tho general magno tanco of the concept, and ita application to las may boedly be considero No reference has so far brocas cundo to yooolaur although It is one of the mora obrona d human character I here Avoided the subject op account of tbe mamatisfactory stato of our knowledge respecting its recetto control. The vler hay long been beld that the distinction between the presence of brown pigment to the eye and its absence, which gives rivo to the blue grey shades, u mal-factorial, brown bola dat at. The appars to be connect, but it in undoubted ore-dimplication. There is a prospect, bowever that the ubject will be peally advanced in the near future. The palot to which pedal attention must be drawn in the ·TAI AOTION OF THE GENES dicamatance that i home you are the extrema albino (to whak bect pigment is abrent from the tapetum) aro bloc, due to a rottalng of light by connectivo, los brown placat bas deposited to the tri. Howear when thl oooon it does not take place until after birth, so that the cyos of Infants ano wally bugs, whether they tro destined to roman oor pot. It appan bilgtuly probable, MOTOOTET that variations In the nato of deposition of the brown payment and the tume of Huppearance are responsible for some of tho dillamco la bunda eye colour and that thero ero genet cally controlled It is stilling fact that the samly born bumsen baby pouce certain faturas boally found only in the foeto d other mammals, the cranial forme, for bostance. This circumstance bas been somewhat over-stropod by Bolk (1070), who held that a procen o foetallation bus largely bem Iespoodble for bumen orolution. Thus red to be an aguation, yet it is close that an alteration in timing, auch u the delay in clonero of the anunlal qutures and the perical lengthening of the baby phers, bas played on Important part in the establishment of the dotnitely human chemoten. Doubtle they have been prodooed by selection favouring ftes which dow down nito al development Verletion in rates of powth d dovelopment are often to bo obeerved among embryou, even in the remarkably content cyron ment of tho minimalien uteru. Thero must be lerrey penetke, and represent the type of ywiston anleblo for puch cotina Some information onista upon the manner in which a few otho buman pene prodoci thet effects. A doglo factor troendro la operation, prevents the formation of an oro oubling Ven to oldbo bomogentlebo sad (mbetenco formed in the break down of tyrosine and phenylalanine) This batermedlabo product thercloro ppear to the urma, which darkona on tunding Tho defoct ba koowa u Akap toourle. It tends to produce athrite, and wally louds to blackoning of tho bones uod cartilage (Hogben, Wamell, ind Zeve, 100 The boormality just descobed may be ·28 OLXETICO JOL KRDIOIL #TUDXXI. compared with phenylketonure, in which . ungle factor produces a mocentre metabolla disorder leading to the cxcrction of phenylpyruylo scd la tho urlse. The maio 2010 is responsible also for what appears to be a very distinct chloch, unice phenylketonuru patients are, in addition, meal defecture of low grada Finally It will be instructro to draw attention to a con dition which can alweetbet tactically or commentally This is diabeta Inapuu, the child symptoms of which are intense thirst and polyuria It w due to a angla boctot hetero zygous in expression, which interfere with the action of the postestor lobe of the pituitary body of this, the disease the doct consequeno, so much as that it can be prochased ale by e lexon of the posterior lobe of the pituitary resulting from wyphoito meningitis or other caruca. In euch altum trom us this, the interaction of beredity mod curlrontot ba rather clearly revealed. It will be apparente, lodeod, that fone Allecting the operation of the endocrine organe Day be responsible for important and widened cocts in the body Others have not w far ben halysed in lart beat they are known clocwhere la the Mammalih. Turgenela Itupoouble for reseve dwaning in mice owing to its action on the anterior lobo of the potentary which is demonstrably detective Puutary gutt allow mch dwarfs to attain Searly to din alte Studies on gessetto pbysiology and on the totaruction between bandity and environment, to the vident seti, Aro gently beeded in Klan. With all its limitations, tbo ribject could be canadenbly wounced even in the proucat state of our knowledge. It & one to which the sitention of those interested in bumen gauettes should specially be directed ·CILAPTER V POLYMORPHISI L LTLODUCTIOX POLYWOLPOIN IS A condition of exceptione interest and Importanet. It may be defined as the DOCUTODOO togethe in tho me habitat of two or more forms of species in Roch proportions that the rest of the cannot bo matn tabned by recurrent mutsbon (Pord, 1040a). It will be belptal to Emplain uod opend this definition, and then to con dider its implantions in omne dotell. In its curtier Heges Ebbe account may spear bat little related to the practical needs of human genetics. It will lato become apparent that this impreelon la erroneous. Some knowledge of the theory of polymorphbar is invaltuble for a clear underland tog of the blood proape und kodrod phenomen. It will bo weer, moreover that much theoretical analy provides the coly bads on which certain comclusions of tmportanco con be reached. Any specia may urumo distinct form in different regions, u the white, the moagulles, and the negroki ruco o man. That is googenphical relation it is not an cumplo of polymorphlan, the dention of which is no framed u to acade it Only when the forma in question perdet together la tha una habitat y dear-cut entities on it bo raid that polymorphlem is established. But this must be distiodabed from the pocasional megrepatoo of peos having dhdrantacoou eflects. There are diminated by selectha and consequently are maintained in tho population only by raro recurrent mutation. Furthermore, it on bo shows that the spread of genes plying the even to mlouto dlustratages will be chocked at an early stage (Flabet, 185041 As well u och upfarounble penes, it be neocmuery bo to conder those which are neutral es regule purvi al nalot. Howie haber (10805) be demonstrated that, lo arilor ·100 ORXZTICS TOE MEDIDAL #TUDXXTE to produce clectivo neutrality of the kind, the balance of udvantages between contrasted allelomorphs west bo artit andinarily exact, so that rich grocs must be very rareIn addition, wtbout the help of selection their spread through the population is exceedingly slow Indeed the number of individuals whleb possess a goo of approxluzately rutru arvina) nitro cannot greatly exceed the number of genere tous kince its accurrence, it it be dertred trom # dng's mutation (Fisher 19902). Furthermore, with particulato Inheritance, mutation is so rare (pp. 01-5) that its recurrent nattro cannot haster the proces very materially Therdoro the spread of aich genes will often requirt & perbod of time vut u to fall vetado the salo at lout of minor orolo- Bonary trende Wo are not berd concerned with environmental variation. Setting the wider and bearing in mind the considerations just outlineil, we may be fairly waident that when a form Occuples even two or three per cent only of glome popula ton it wť probabły power some advantage. In thane circumstances, it may ether be la actual propea operator or eleo it may be maintained in a constant proportion by . bulance of selecting agencies Then two alternativet, respoctirely namod transient and dalanard polymorphim (Ford, 1960a) each represent can ditions of outstanding interest in tho transient type, Larm previously nuro spreads through the population, which becomes polymorphie during the proces such as Occurrence ho perlupa amin due to change in the environment, which give forme value to a character preriowy dland ranta con Formely tha mu dot ranked a polymorphim at alle for the term was reserved for the disilact dan of pbeoocoa la which stable nation and Lavalred. The frequent difficulty of deciding in what isteseos stability b li fact stained has made the Lochun of the trasient situation practical secrety To take as ennple black forms of many species moth bare appeared in mastufacturing districts od baro larrey mupplanted the normal pelo types that during the laut Any o naty Fan (ico Ford, 1937), lyhilo this change ·POLYVOLPHISU 101 wus in progrex, these populations were in a state of troulent polymorplom Tree, or balanced, polymorphka uns involvo equilherm between opposed selectire pendich. As already pointed out a force will wally pour roma dnantago Le ut hus spread through = population to any conuderable extet. But normally this vill loud merely to transient polymorphine Stability will be attained only when the adintage cafardd almbahes, and be inally cooretted lato didnatege, u the form becomes proportionately commone Sach check to the progress of an initially drutagrow game may or may not be genetike. It will be bopaned wtomatically it tbo beterorypoto in at a greater ndrontero than the of the two bomoaygous clanak But that are instances in which it to actualy underabilo that tho forma fa gran beterogeneous population abould depart from definito proportion, wheti constituto the opthaum. Thos the abstence of the two robadtuchon which fall ithin the definition of balanood polymorpblun. In each portas they aro molntained at an optimere ratio which boa pedonally nour quality Wo may be condent that way modication of the ser determining mechanlan leading to fncreux the frequcocy 000 the apeno of the other would be opposed by selection Other, and remarkable, fastenoos of polymorphlam to MAD occur in addition to wear. Thoso must now be condered. IL TO TASTE TOTT The ability to testa pbenyl thlo-ures to low concentrations bu abready been documeur Amplo enumph of the work of Heodet's fint lax (IP 0-15). It us be recallol that those who on detect this montance pouw rede T dominant la llech while the inability to do so we reconeiro und dox to the operation in allelonsorphio pals th Whea both partits are noo-tastes no 1 thelr children. Tre a detect ob robotloos of a parte por me or hoe O ODOE Das type mouly do wie into 100 porta pe plan ·OXXXYICI TOR XEDICAL ITUDIXTS to produco chiective neutrahty of the biod, the balance of udrudtage between contrasto allciomorpha mut ba eta ordinarily act, wo tort Arch goa mut be vay not In Addition, without the help of selection the proud through the population expoedingly slow Indeed the pomber of Individuals which passen a gene of approximately neutral kiral value cannot greatly exceed the number of good tion ance its accurrence, It be derived from single mutation (Fiber 18900Furthermore, with particulata Inheritance, mutation is to rare (PP 01-4) that it recurrent rature cannot hasten the proces vary materialy Therelord the spread of Rich gese ml often require persod of time # Vaata total outudo tho scalo at lunt of minor colotionary trende Wo and Dot herd concerned with ensironmental variato Setting the wider and bearing landed the considerations Just outlined, We may be faldly contdart that when a form occarder ever too or three per cent only ol giron popular ton it will probably postele samo dvantage. La there circumstances, it may other be la actual process of sprendiamo or abse it may be maintamed in constant properties by * balance of Klective agenciu These two alternatives, respectively named transient and balcomand polymorphia (Pard, 10102), assh report of ditions of outstanding interest La the transcot type, COITA previously mure spreads through the population, which become polymorphia during the proces such as accurTENCE by pabape almay due to a change in the eaviroantots which strer some value to a chance pronunty dosudrante con Formerly this wit dot ranked a polymorphism at alle for the term wu reserved for the distinct dam of phenomena in which stable ratios are tarolood. The frequent difficulty o deciding La what Instapoes stability to in fact altamed het puude the indudon of the trandent stuboo pruction DicotyTo take a cumple black fordus many species of moths have appeared in parutinctutoy district Rod bare lerrey ripplanted the normal pelo types these dunng cho lot Afty er duty san (sce Ford, 1987) Yoke this story ·POLYTOIHINX 104 reality of och polymorphien in man. This is a puficient Importanco to nat a beic daclpbon It appared fost conceivable that a study the unthropold apos might prondo decidive erldesco that, long-established polymorphism is at out in maintaining at optimum proportion the genes controlling this taste effect. The pond bullity a auch an approach nu realised, and tested pueden fully by Füher Ford, and Huxley (1999) They found that taste' ud pon-tastens arkt in at least two spodles olaps, the ong-utan and the chimpanzee. There animals can bo clused for this character without risk of couturon, and the Lord of perception proved to be approximately the amo u that at man. Uang the chimpanses, it ww found that out of 17 indiriduals camined, 7 or 10 per cent, wero non-tastan, which therefore carat to approd. mately the same proportion among them as in the human nace. Without the condition of stablo equilíbatum, It is hardly coocenable that the generatio should buvo remained the amo durtag tho million or more generations and tho reparation of the anthropold and hominid stocki Wo the havo ovidence that over this period the heterozygotes for tho ovidently valueless character concerned her enjoyed molectivo eruntago ova the two bomosyroter, and this both to the lengo of the evolving chimpansoo and in that of crolving man. Whad the advantago lice it would at Pont be bilo to speculate, creept that it presumably of physiologiaal natura. Howeva of Ito autence there can be no room for doubt M. D KLOOD-Gours (c) TU, A B Sola Simlar ta polodple to the polymorphlon of the tuste test that forotrod in the bomen blood-groupe The arom Ito portant that they must be dlacussed in some detail. Care frequently are ta which it nocery to trade blood from one individual to anothe It had long been robbed that though tch procedure is sometimes bituly ·thardcore, that the correspondlog zglutinogen and glotiata The clutinogens (antigos) A und B wally oocur who which these produce. This they are geenlly found in mal 104 OBXETICS TOL MEDICAL STUDENTI Recental, at other it is attended with reson and atten fatal consequences The technique wu therefore medlem mil tho bado undedying auch dikigpuncas had been analyzed. This has now been done, with replts which moet beleily be summerleed. The red blood corpuscles sometimes con un poutkou, Abstances which react with other called applica prezent in the plasms of another Individual. When they do 30, the corpuedos run together or agglutinate, wo blocking the blood reuela In trenduston, it Lomportant not to use blood wbone corpuastes will be egglutinated by the place of the redplent. The reverte procedure that of injectlog blood whomo plasme an egglutinato the recipients corpuscles u generally bermolens; for in the drcumstance, the door pluoma la too much duted to produce detectablo affecte Several distract types of applutinoget, abeo called at adt. Tbo to most important are known u A and B and the corposle may contain both, one or the other alone, or nather of them. Individuals therefore may be placed in 000 of four dance, called AB, A, B, and 0 depending on their content of these substance ID dhe AB both ghuth nogens are present, and in o both uro abant Tho lo tintos In the plumme are also of two main, and correspondine. types. There are called and B and thoy aro aloo known u antibodies of A and B, or anti-A and ant B. They react with solutinogens A and B respectively it is evident, can Dover coedst in the name individual for this would be fatal to it on the other hand, en gelatinogen or an apple tinin ba Dovar absent from any person in whom it can palds ocour Thus those ponering AB or egglutoogeas alram CRITY A or both segtutinins respectively The Ames tous of the arkstence of elathogene In the absence of their spouils glutinin in renow glend cells, and may appear in the correttore quantities in ten und lo anae, bat they occur in ulivi sad ·POLIKOIHINX 100 fa semente mach higher concentration than to blood. Thb b doo to the action genoS dominant in elect, which allom the secretion of them platinogens, while the recor tre provent it. It seems that between 18 and 18 per cent of the population are of the letter type, to which tho alatinogen are about from the mudou pland cells and ther secretione It is clear that individuals might be closed with referenco other to the applatinogen O Å BO AB In their arythrosytes, or to galutinis , AOF Bln ther place. Actually u be the former plan which is adopted, and the standard nomenclature for the groups 0 A, B, ad AB. This thocno odrically recognized by the Health Committee of the Lap of Nations Unfortunately numbers based upon to conflicting my temore cometíma employed for the blood groupe Groups AB, A, #, and were nombered 1 to by Mous, but numbea 1 od 1 uro transpored by Jonuky Thle has repulted in much comfocion, und probably to sedenta ta trandalon The numben aro not now amployed In wietlio publlosthood, sod they ought never to bo med. Thoy ero only mea toned here because one or ther of the numeroal syatenus (that of low in England and sometimes of Janary on the Continent) b will adopted by a mall, and it boped decreasing number of institutions, 8inco any dopor may be mad wrbo doce not ourty tho glathogere corresponding to the platining in the place of the recipieat, the porabili bes blood tonusloa on cally bo determined. They uro represented in Tablo A. Group O corona tho du know wherul dodont dDco the blood l compatible with all groups (Tablo A, tot horisontal lmo withia the table) Honeve the blood of group but ther own is incompatible and sometimes fatal to them when they are recipients (HL, fint vertical Loo) On the other hand, the AD group can wupply blood for po froup bot ito o (Urd, Loret barbontal Ipoh, bat an roctivo blood from any groep (2, Lost Terthal HD) The blood group of any individual an be determined by ·109 GEXETICA TOL KXDICAL ITODEXT: poopies concerned and the populations among which they dwell and, stil spora important for our purposes, the stable nature of the blood aroap natia mithin giren nucem Theko blood group and controlled genetically by a system of multiple ulctomorpha Group 0 1 dua to the operativa d & pair of allelomorphic gezet us recenive in check. The groupe A and B nro ench produoed by . dlfierent gezet mul station (Gox G) at the locus of Both the A and B Froup are domlasnt to group That is to say who gero typo G Wand Ge both ging niso to group 4 and are best dlatinguishable in their clicct box are G P 1 & prodio ing group 2. However the genes QA and interact to prockica tho AB group, which genetically be GºGº This therefore, as group O Cabavo but a slaglo genotypa. It will bo evident thattrom the point of view of bloot grouping the results of any marriage aa bo predlotal within ortala limits. These can readily be deduced brow the Inforonation just provided, and they are litod in Tabiha G The importance of these facts will be discused on pyh 116-10 Type of Hertha Blood-TOUT abecot Amor etuksen OXO OxA OX AXA B x D AAB B, AI A, AD B, AD A AD AD OXAN AXAS DXAD ADX AB Tulla C. To typer of mambuge un posible Ith respect to the Lour Hookupe 0, A, D od AB Tens are Hotel la thu Oru colume In the record como u be Doxand the blood roup which alsot apa anda thely chte ·POLTROPHINX 100 It low powable to obdivide group A, but not group B. The rouction of watoogee A to gylatinto may either be strong (group Al) or waak (group A3). Tho diferenca between them are pot believed to wiect the foty of blood trandorton, so that it is not than to undertako tho Labour adratulating between them in ordinary blood torta, cocoequently Tablo A has not been pubdirlded in respect of them. Catata indiation appast, bo wever that it imler In un A to A transforon eh ayy to wo the same type of A w that powered by the recipient Taylor and Prlar (1988) found that in England 4pproalmately 17-0 per cent of group A belong to the At rection The recorded proportions in Denmark and the United States ute higher being 34 und 31 8 per cent respectively whilo in the nativo population of Hewall group is a mid to bo abent (data from Wiener 1000). In gconal, wo may como that about ono quarter to one ifth of thowo popening A.ro of tho At typa Additional, ad correspooding, groupe A1B and AaB of coarne adat in holler proportions within the Genetically groupe Al and At are controllod by two ma Gland + Lelomorphio to 000 soother and to and They form a multiplo Ildomorph secten in the order GG G cech of which is dominant in elfoot to those below it c bowever though dominant to s interact with I and Qi to produce groupe A1B und ASB respotiroly It win bo pparent, therefore, that groop al may carry fame or but not in dngi donc, but that group A1 and B an only carry ? In addition to th sparcot Barnembering that not more than two of thoro groo oo wach to the one individual, the genetics of the blood troape taldng loto account the subdivision of A lato groupe Al and As, can cudly be roched out the refinement naturally lunits all further the possibl results to be ob talned from many of the rartous types such infor Dution, additional to that provided to Tablo Ci diren In Tel D. AB group ·110 GEXETICS TOR MEDICAL STUDENTS Verder Blood proape absent un ehlurta Hartan Blood group abat un ahla Al XO XO A1 X AI AS XAS AIXA ΑΙx B AXB AIB XO Аав хо B, ALB A2B Al B, A1, A2B E, AIB, ALB Al B, ALB, ARB B, AIB, AB AIB X AI AIB XA ATB X Al ABX AS AIB XB AB XB AIR X AIB AIB X AED AIB X AXB 049 O A2, A1B 0 0 A1 AIB OA, AB 0, AI, AIB O AI, AIB 0 A1 AIB A1 AIB O A2, A1B, ALB O AI AIB, ALB 0, A2 Tablo D. Herrhago fo volving group A, when the bub divided toto Al sod Al, and the blood-groups whlah adook Ppour nong thair children. Yet another pubdiválon of A, groap As, has now been datooted, having « still water reaction with agglutroln - thao hu A2. The data of Fredenreich, one of its discoveren ergrat that rather less than 0-8 per cent of the group belong to As. His investigation indicate that it is inherited and that it is probably detained by yet another abattuton (G) at the locus of 8 wbou efect may be recenziro to Gli and G4 and dominant to Prerimably it Intents with a to produce a group ASB of great murity I there Ludloutions are rubstantiated, wo havo & multiple attelo Dorpb series of Avo terms at tho locuit G GuGu Q and, and the genetia of A8 could be worked out on aimilar linas to those of the other groups. However the tentativo nature of the information at present anulable on A3 does not mako it damnable to provide tablas Wustrating the results of the marriager lavolving It Furthermore, even if the could be done with confidence they would be of religiblo Yuwo oping to the nuity of the group It abonkl be aplained that the nomenclature of them and other blood-group pon adopted in tbo put hu been ·YOLYXORTAIS 111 unatisfactory The games for groups o A and B ban themelres been ald O A, and 8. This breets tho rulo to be adopted in the Domeoclaturo of moltiplo donorpbs (p. 30} that the ame symbol, distinguished by . Ali, would be used througboat. The allelontorpluc nature of auch more i then still uppareat when the dous alone aro em ployed. The too of Great lotters should alnya lodonto ta ut different lock. Furthermore, to represent in the same y the genes and the blood-group which they control bavites a cooloistoa which should never dot that between the chanatos nod the genes responsiblo for them (pp. 90-1) La addition, to reading works on blood-grouping, it often by no man clear whether particular letter refers to pero to procp. This can only be determined by a careful Aody of the pamango concerned, and sometimes not tben. Abu tho we of the cypher (0) for a reno, in distinctoo to another letter for los allelomorph, suggests beenco of gendo material at the locaux concerned, nad of this wo bave no cridenco bat A moro intolerable praction is sometimes adopted, in which the gene for groups A und B art designated and B. but the gene for group is called R (to wgreet the recentre) tho stotypo then being RR To represent two oat (three fone by tho uma letter - the groupe they produce, and tho third by a letter quito diferent from its group baring Dothing to repot alelomorphuom, lead to a confusion for which there is no paralle In genetio Dotation. I have thero- Loro employed the ordinary multiples lielomorph notation for the blood-group reet; ndng : (group) for that with tho recendre edicet, and the capital and Rules for the decat DADE, u would be done in any other auch wie (5) TK V N Series In addition to the egglutinoge so far dhuned, other edat in human blood which Interact with glotinn pricat to the plems of rulow animale Only two auch rria here to far been reled the tut compres two tutipogee kord - Vuod Al human red blood

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·POLYKOLPAILU 113 toglo potr ol aliclomorphs without dominance, cutted in . dulant chromosomo from that containing the locatie Groupe and Neo bomosyror, and JIN W the hetero 7 dan Tbo gorses tarolmod may bo represented by a B for group II and PB for group N o that HN bus tho genotypo R'R Here, w in the 0 A, B series, I havo do parted from the current notation, to which the rene and the dames which they produce uro represented by emlar Typ Verder Beool group boot u chitra NXN NXN HXN 1 X HIN NX HN IN X MIN NIIN M, LIN VN N r Tablo E Mercepts toporto the UN od UN blood proup and the type obloh cannot appear amoop the Lettem, o obucurtag alobomorphlom. Hy rouous for doing un wondeatly aplained on pp. 110-11 Conecquently I havo tuned the more letter for the two phases of the amo rone in cofournity with ordinary resetlo usage R being chorom (with relero.co to nbbit kium) with so inter modiato beterdaygoto it is not detrable to employ aapital and coal Letters for tho respectin ellalomuphlo state, there should ladiesto dominera Thon, I hato adopted fized letter with . Trying parts, which demonstratos both wielomorphloe and the relation of so to characto It courg only Docemary to pply Vadds Ant Law to decorar the result of any meslegs far us the WN Klab concerned Loreter thb information is prorled to Table E, and its onthoudce will be dead on pp. 115-10 ·OINSTICI YOL VEDICAL STUDENTI (c) Tu Na Group (sco alto p. 152) It has recently bees abown that the human red cowpuncilor sually contain an entipena eulled Rh, which reacts with lamuno sa prepared by fojecting nbhita or gumpalgt with the blood of rbeau monkeys (na Taylor 1013). The promeo of the theatges is inherited urkmplo domlouant, It occur in about 80 per cent of the population (cabulated on whito America) Racial diderescut in frequency at Izomever now mom, u is the orience of more than one klad of Rh, analogou with the dierent forms of A. Antibodies for Rb do not normally ocaur la huxzau plasma However when blood containing the Nb antigea is given Oo of thout lacking it, alight bacmoolyais may rewall Rb antibodles art the produced that Rb blood seen at later enn fundon my hare gravo rarita Serious reactloos arc weetne obrerred la mome true tured for the Art ume after the birth of a child (or mir arriago) There seem to be due to lindude antibodies fordord in response to antigen prescot foto foetu but shecat in tho dolber of them, ab appears to be parthularly knportante Taylor suggests that the pasage through the placenta al such maternally formed motibollen may be the cause of cry throblastou toeulle a huenolytuc dean of the Dewly lacta The detection of buman Nh antibodies may be difficult ar imponebla Taylor therefore advised that Phrncy tiro Hood should be used where potrble, for repeated trwal usians or eves for a fre transfusion to a recully pregnant Puncil APPLICATIOX A koowledge of the A, B blood-group senas s of contro entential in the wide range of cues to which trubalance s denrable. So it who in medko-legal work, uleco blood main can be used to their correct blood-groupe thom usting in their kentication. The resetio speck of poly morphim, exemplified by the usko test and the two boot groop series, is dito at itaportance to practitioners bath Lor its legal and its medical significance.

·POLYVOIPAIS 115 It has been demonstrated in this chapter that it pomblo to predict, within oertain Imits, the blood groups which an per utook the children of parents whomo pooping ba know. The type of evidenco is now admitted in Legal proceedings which involve doubtful paternity and modicul men may find themselves alled upon to giro apart ovldeoco h ruch cure The Information which they will require is fontarted to Tablas C-E in the chapter Lvidence of this kind may of couro bo required by the party in divorce Lod Hodred proceedings. It may be shown that child cannot be the oddspring of its logul antha or ternatively that a man cannot be the father of a child attributed to him. The revert procedure that of proving thut, man must be the fatha o particular chid, u pot fencible for this rouson, tho tables art unanged to abow which blood-groups cannot yppear among tho children of particular types and marriage, u this is the information requred in practice In all wuch circumstances it will be well not to no tho toplo O AB AB series, in the bopo that this may provido the required data. If it does not do no, recouru ona bo bad to the 11 N, KIN wooring and Anally groap A abould bo subdivdal (1 present) It sbould bo omphadeed, however, that pedal asperience is required for work on thero latter proape, od this should not be undertaken atoopt by an apert Tho ning of powdbilities AppHod by all throw of there methode la considerable. In this matter the oppert witness must guard html galost en obras althcare. Ho may be asked, 'I. It not true that genetic factors are abject to addon and unpredict able changes, alle mutations und (gruntung thu Lact) da not ordena depending upon the inheritancowbally w post? How In fact, aan it be swerted in any legal own that the gene the factor la question has not changed in the way!' The toformation required to a thene quortlaas ba beca pren in Chepte IIL However It may be covenience to provide a correct reply to them here The bereditary mechanion of at least w higher arrania ·116 GENETIC. TOR MEDICAL STUDENTS to the particulato o Meoddlan type, which depende for its operation upon the estremo permanence of the bereditury factoo themselva. Ware there to chango (mutate) in as many Mode fodindul in crea a few thouhod, the system would break dowe A study of such mutatzans throughout the widest selection of living organtons demonstrate that . mutation nato of 1 to 50,000 indiriduals extremely high, cod this frequency & hardly ever acceded Inbetanco in man Loon the mimo type, and there conandam oro stretly applicable to him. But we are no longer dependent upon Lalogy for a bowledge of human mutation-rate. It has now been pooblo to study this m heveral instances (pp. 01-8). in which it proved to be, when most frequent, of the humo order of runty u in other animals (100 Habane, 1980) Wo aun therefore be confident that the error Introduced into blood-grouping by mutation is not preater than I in 80 000, and is probably lem. Such minuto chances aro out skdo ordinary asperience. Few legal y an have been decided during tho prouent century in which the possibility of mistako wu pot condderably greater than this Wero. chanoo of aror for greater than that introduced into blood grooping by matation taken into consideration to legal procedure, the law could operato no longer From the medical point of view the human polymorph broom, u exemplified by the taste test and the throa blood group chien, ero of importance from several spects. First, they poorido a means of marking ahromosomes for Inkaro soden, tho value of which to discused on pp. 197-& They aro apecially adtablo for this purpose Haco a largo pro portion of tho population is beterozygous for tho getes com trolling them. Secondly the light which they throw on paternity Bready exploited from the legal uspect, bd datanco in chochong tho ralidity of a pedigree to which som inbadita condition appears u . naty or lo aprened In un aceptional muy In there circumstances, onglo aures may greatly attest tho lnterpretation, and the pobility o doubtful peternuty should be investigated carefully when Taxis ruspected ·POLYHOLPHISY 117 Finally we most return to the general principles outlined In the latroduction to this chapter It there shown that the po controlling polymorphiam ll not usually bo or qual marital rahe The correction of the view has now been demostrated a respect of the tatto text (p. 103), and theoretical condations indicate that it may bo equally uppboablo to those of the blood group Kria und 8 Here the prodl still lucidne, but colence may yet sccumulato to show that the prin yalao a tho dulcrent membent of then werden is not idential Information bearing on this matter might be obtained from stody of the blood-groupe d abortions, #1-birtbe, und children dying in infancy It Poncible that the double dominant group (AB) might be tndaly common among them, Indicating its ecen allmina thon. However Prolour R. A Flaber has lately wrested to De that it is not too roboto pondbility to rock cridan.co al dimerential survived from a compartion of the blood-group frequence of the young and the oldały We can hardly support that the blood-groups represent bostanca o transient polymorphis, rather they must bo of the balanced typo (p. 101), modated with rate which havo long remained stable that tho proportions of tho group should very widely between different nous does not ppour to contradiet this view The genotto constitution of tho mare drattoct of the human races most differ rather on derably providing Internal environment whose optimum boditions may well be disimilar On the other hand, the evidenco doved from palo and from Jews (p. 107)indicato that the blood-groupa Ithin ruces her attained stable proportions which must have andured for boog periods of tooc. Furthermore, the anthropold epos are tho only mammals in which are found antheon Lentical with the human d and D In this respect the lower Pumata aro do Deater noun than ure many other mammals, but in tho anthropoldo the groupe are tho me u In Oatserna It L strongly marested therefore that this grouplog is rey dent, bering been oro red to the common ancestor of anthropolita und of man ·LIS OEXLTICI TOI WEDICAL STUDEXT! Theo condations of coarso apply not only to the OA B series, but also to the H, N WIN groupe Indeed it etabliebed that rubatances corologically related to the andgere odat in the chimpanser, bat dot to lower monkeys or in other mamak (Wienet 18.39) In the emplo fonctia situation of the L N IN said, Itablo equilibrium would be attained the beterosyrotu dla wero at an advantago compared mth ather bomoryrote This would lead to an area of the WIN group, though petu haps . mimte one. It to noteworthy that auch an cook more frequently recorded than a defctt in those bostanco in which the group departs significantly froth expectation! ("Vienot 1009). This bus been commented on with purpette though, in Duct, it be Dot unreasonable to anticipato much an eflect. However It probably due to store in technique for no wch access to appareat in the exeptionally areful andler of Taylor and Ikeda (1950); though one might hart pocted mistake to canoe ono another out in data dained from the combloed results of mamber of workert Yet it quite poolblo that weder absorption, or the presence of tutinin and loading to an apparent cucer of the AIN daw, may be more frequent coult than over-abrorption or tho we of falda of inruiscicot strength, tending in the other direction. Clearly the matter is one which mients taratigation in the future The implications of the different habiliter conferred by the genes for the testo test, and powdbly for the blood proops, cannot bo predicted in the present state of lowledge. It to conocirable that thero gnotypes may not be equally resistant to certain duets At any rate, the ordeta within the population of sections having mequ lability Anull and costre though the datinctions may be, han deserving the careful attentioa al medical practitions and pahups, of bannnco com 1 The apestation that the proportion of the heterore dhe pe) world be equal to tula the prodact of the quer rooutbe other two od Napist ·CHAPTER VI VIETHODS OF STUDY IN HULIAN GENETICS IT WILL 11 ordent to those who read this book that further research on human genetion to much needed. Indeed, the abject to only fost rashing the start at which it on totally be applied to practical problemen, wo that additional Inowledge will now site preatly to extend ita noope. It L by the co-operation of medical ma that auch advancos sro hikely to be schoved, and the main purpose of this chapter box to indicato sotto of the man to which tho necemury Infor mation may bo obtained Obrou restrictions are imposed upon the study of genetic to an organlo punh u Man, in whilab uspeolauanta uro imponible yet certain suplo methods edat which have been deed good to Rumount some of there, and a relection of those will now be discused Some advico may be helpful both on simplo means of analyus and om the type of data which it le most betul to amen Howoven many methods of great importanod to human genetton ero too tactinical for promentaton hag and information om them abould be obtained from specialist woda Thu reform ta portucaler to mathemation procedure In addition, this chapter throw further light on a puumber of genetto phenomena Some of there have not for been considered while bele relanco only has been made to othed whtoh aan uw bo explained moro fully L LITOITARY QUOTATIN TROUE The rudent of humed povetio paust rank mathemoutsoul analyse among the most important of his tools, but that Rubject to ano which won herily be undertaken to a book of topo. Fortunately however then cute Dumber worla specially devoted to it from which all the information ncccery an be obtalued. One of the Loomch acptopel importera thet It must be mentioned at the ontacta thlo a Elsbe Sulinis Urheds for primera olan ·10 GINITIOI TOI MEDICAL STUDENTI I would also strongly recommend an excellent little tratte by K. Mather The Veam of Lembage i dentity Yet there are a few metrial considerations which uro po doplo and fundamental thot they may belony bo decimed here Tho fint of these reen to the distribution of goue in Popoletion breeding at random. A pair of Jelom phas uutosomally tranamitted an out in three gobotypes, the two bomosypotas and the betero yhoto With nndom mating their frequencies reach stability to a Anglo genetation, so that tho proportion to which they cour retrien constant unti dlaturbed ether by mutation of relation. Those sende will come tho clamos to strumo neu quilibrum tn tho nart genution, which will also rematn tn stability mla rubject to extraneous modification us before At whatever proportlane of its los santosomal may the frequences of tho three clamo alwayu bear. Amplo relationship to one another That is to say tho number of Individual belongiog to the beterozygous clam (H) is twice the product of the quere mote thow forming the other two clama Thau ff tho number of individuals to the homo wygous dominent ces (D) is pl and in the bomory poos rocando el (R) is go the three genotype, D, E, and R. ura distributed in the proportion p' Spec This to a condderation of much Importance. If we know tho proportion of recoudra in the population, the notion of the domment phonotype which is composed of hotero "Trota b directly calculable. Suppose a discux doo to . Ample receptro occur on the arerigo in ono Individual bon ten thousand, then approximately 1 percent of the popula ton ero heterozygoto for itt "ye ko at anoo how utoalabingly widespread in the human co mngt be tborond whiteb pred to receiro defects o nurt that they are judood to bo little more than medical castles The gailcance of the concluded will be discussed ca p. 180. Sappors, on the other hand, rc conder . peas wib ·WCTRODE OF ITUDY 11 heterosypus manifestation (1 saaled Somirant) Po may relu bow often can ito bomosypou creat be studied? Icon dividual ta ta thorend pouces the heterosypous cancter then the beterozygotes forty thouand time commoner than tho domimnt bomosypots, which therdaro ppous only in ono Indirdual in four hundred millbon. Many al the non-tooentro condition in Von aro neret than this, so that the difference in frequency between their two homo- Trou en is yet moro rast. It w pointed out on PP 11 cod 87 that though many of the nro condiboas found to Nu uro described u dominante thu . puro wrumption to nadly cvery one of them. It will be ovident from the renc-trequencies involred box dificult it puomally to europare them to their bomo ypous and beterozygous pharet, und until this is done no concludon on their dornance an bo reached The aplanation of dominanco-modification doveloped in Chapter IV depended upon the condideration that the steet ol any nero gene m almost alwayı bo fodpod in its heterozygous stato, the frequency of the bomosypoto bring Depligible. The bands for this oration will now be dar 17. buvo wo far been rookwing the distribution of Loto- Honal peppe tn population mating at random Hovover the normal typo or mm-lokere (total sos linkego in the X-chromowotne) Lands to comewhat different dtuation Peste stability to not immodletely reached after the pro dating trequenca havo bem disturbed, but the propor toor In Aubacquent grantkoos candidate about their dow quilibrium veluo. Soooodly no boterosygoot repolypo ccate to the male (atelotly speaking to the heterogumello 9) Aoco that kar pomenes * Anglo I-chrononomo oaly The poolblo genotypes of penes outled in the non-pabeing reglos of the curomosomes, and the proportions, uro #follow alon D D R P P 1p2 R 1 ·01XETICI TOP NEDICAL STUDENTI I would do strongly recommend an Icellent little treated by K. Mathe Th Veasurement of Labago tu Bond Yet tbero aretov metrial considentom which uro po Amplo and fundamental that they may bneily bo duced bere. The int of these reiers to the distribution of gena la * population bacating at random A parr of allelomorphs uutosomally tranenitted an obt in three genotype the two homoxygotes und the betero tygote With random meting their frequendo reach stability to a dngle generation, so that the proportioon in which they coCur retain constant tuntil disturbed other by mutation of selection. The agencies o cum tho como to damo . new equilibrium to the next generation, which Ill also roman to stability ulon sabject to atraneous modifcatio u betare. At whatova proportion of its loci un autosomal geoo muy adat, the frequences of the three cena almaya bour . duplo relationship to ano another That is to my the number of Individuals belonging to the hoterozygous claw (H) i twice the product of the quero roots of thou forming tho other two duo. Thus it the number of individuals in the barnoygou domment dom (D) bo p' and in the bomorypour roedvo con (R) a ql the threo genotypes, D L and R. aro duobuted in the proportion P ep2:9 The e coridaration of much importance. It wo know the proportion of receive in the populatiog, the Inaction of tho dominant phenotype which is composed of hetero ygotes is directly alculable Supporo e discuse dos to Amplo reoeutro ocents on the averago in ono individual to ten thoutmod, then approximately 3 per cent of the populi thon uro beterozyrotes for Iu Wo so at an.co how utaobab ingly widapread in the human naco but be tho gepas which gtvories to reccutro detecta rere that they are judged to bo little more the medical curiosities. The significance of this cuocudoa will be discused on p. 104. Suppoes, on the other hand, wo condder o gece ylth ·Part, stability to not moodustoly reached atte the pro tood in absequent renerations date about there wata in the malo (strictly spandey In tho betaugunotto a) doce that was por unglo X chru dopO00 only The possible rootype od rena canal in the doo-politog rapon of the X-chrom, and the proportion, vo XETHODS OF STUDY bateraryros manifatatko a salad dominant'). Wo may well ak bow often an its bomodygow cllect be studied Ilco badirkhul In ten thousand power the betarorypois duructa, then the beterdayroto is forty thousand toas com Doner than the dominant homosyrote, which therebro peu cnly in 000 sodiyldual in four hundred million. Many of the Doo-recer conditrons in kos no rure then this so that the difference in frequency between ther two homo sypou cames is yet more raut It w połnted out o PP- 17 cod 87 that though many of the ruro conditions found in Yu are described us dominant this puro waruumption la nourty ctory one of them. It will be crident from the ne-Arequencas foraired bow dildcult # normally to to compen them in thete bomoa you and heterozygous phanh und until thile la dona do concludar on their domioanco ou The explanation of dominanco-modification developed in Chapter IV deproded upon the comuderation that tho sheet of nay rano ponto wm almost always bo jadrad lo lbs baderosyrous stata tho frequency of the bomosyrote beter begligible The Beads for this recition will now bo We have no fer been soviowing the distribution of autocomel sempre in population mating at randon. However the portaal type o meu linkage (total ma-inkage to the I chromosome) Loude to Bowbut dittaent dtuation dating frequenchen bero been disturbed, but the proper qudbetam valasa Secondly beterosyroto remotype be reached llow D R Time Y 977 D P ·19 GEXETICS TOL XEDICAL ITUDEXTI great the Consequently the nto of reoandro males to rendive femalo 19 qdorl ! So that if one individual in ten thomud b. KI-linked receive, wtected malos tre fro thousand time command then attected females That is to ay totally mes-linked reocalve ooddition an immensely moro frequent in malo thun tn femala. The pows on aror which I have staral tits an.countered in medical writings. It u sometimo noticed that . receivo delect occun rather more often in malay then in femalen (perhaps three or four timon us frequently). Realizing that recoverO Klinkego leads to an awe of mala, It bus been rugrated that the gene in quation is corded on the X-chronoroc. With one exception of a very specialised type, thus an dora bo truie in fish arcumstanca Tho difference between recoudra in total sex-linkage is alwayu ro Am Cop of mula, mounting to a low timer the females, cannot possibly bo attributed to it. Morcovea rough antrauto of the frequency of the condition to the popa Luton an wually be made, allowing a comparison between expeotation mod reallation in the so af aflected persons The remains the possibility of partial t-bnluge su pointed out on Pp. 46-8, this does not produce any KOCAtion with me when the population us a whole us canadared. Only within given familiei con mucha relation be detected and this will take the form of a small ace of tected malom in one family and of affected femela lo another Clearly a mell caso o RI among individuals Rulering from u roce uro defect must not be attributed to kilkago unlom it relate to inheritance within a particular famig Creo thon it an only indicato pertul e llokage. Totally sav-linked genes dominant m aprehuon appear to bo very rart. Poobly true dominants of the kind do not dat The presence of the two X chromosoma la tho feruk would allow them a greater opportunity for occurraco to that se. Il the gene were a very uncommon one, the propor tion of homosypoun female would be negligible, so that the frequency of lected mula und fanel would not dilter detectably from a ratio of 111 ·YETHODI OT STUDY 128 Dominent total ketmayo cannot are rue to an eten d'elected palen. Eren un exces dwfccted females amountfog to promately double thet of the elected malas most bo attulbuted to it with ooting, fo.co the conditioa bat any nats extremely nre Dominant partid ka linkage could produco a Alght arrons of the lected in other ex so that it unrecognisable in the population u a whole, but it can bo dirtingulahed in a study o doglo families Soal ocemos o one I umoog afected periods, whether al dominants or of recadires, une poorly aluny duo to the operation of ex-controlod Inhaltanco (pp. 82-8), and at the outact this must be regarded us by far ther post probablo opluontom. Partiel Kalnbago an be d'atloguluhod from It by eroveral of the sa-dietribution when different familla To compared with one another Doo regard to them coowiderations will prevent the repetition of mistako whlah bu bocn mudo on a number of occudown to tho put It obvlornly necemury to catimate the crror involved in Dy geneto calculation. The populations which we wsuh to study ero olly wo large that it is not poudhlo to countoo overy one of their member Yo tbereloro deduco their qualition from emplos which wo believo may be chanctalatie of the Sach featura u the kinatio, or the distribution of regregating clanc, sro directly alculablo o che ampls, but the rolba most then be upplied to the general populatroo from which that emplo has been withdraw.. Carly tho barger the maple, the more dearty do ito attri bata telect those of tbewbolo population on the other hand, the greater the rooiaballty of the sample, the larger it must be if it is to provide information of pro standard of Accuracy The relation which the characteritis fe wmplo bear to those of the whole group an be comod by sppill ations of the theory i arrot To Docery methods for doing o ato giron by Haber (1041). Former for the calculations of this Hod uro odmple that they may briely be omplained bet The probability that • gran reult eball be qullod or V ·184 GENETICI FOL MEDICAL STODEXTS 9X. Aupued by chance may in propriate circumstances, bo determined by calculating quantity called the Standard Error (). The frequency with which a marathon a larro us the standard error (cit multiple) may occur by chadoo is approrimately u follore Standard Korat (0) Probability to be reached by shunga 1 xa 1 in 8 1 in 2 XO I la TO It se convention to consider that statistical dlgold.crbco be attained by a quantity which equal to its standard anar the may roughly be regarded as odds of so I euinst tho result being fortuitor. Tho standard error of a percentage may bo expreced ne: V 100-p) what pletho percentar and a to the total number 190 Day wish to discorer the rex nato at a given you particular district. Sappose that for this pupowo wo obtala . mmplo of 100 individual, and find that 48 par cept of Chrem ane males. The standard error to calculated as #52 and the res natio sbould be apressed as 45+-52. That is to ay tho chances aro approximately 11 that the true mer ratio of the population from which the sample we with drava la within the range 45+7-01 Moreover Naco the 50 per cent level falls within the limits, to have obtained no evidence that the corentio of the population differ Irow equality It may be noted that I wo ad uctually coa uned to tat whether the observed frequeoco woo cold patible with an epada ratio auch u 50 per cat va sboull alculate the error udog that rabo (La V60 X 50 / 200 -354) This camplo abonot only that it is poseblo to stimate the relation of sample to the population from which it * takes, but that is actual ratio may be compared with that crpected to power on one hypothed Therdore it be ·XETHODS OY STUDY 123 propriate means of testing the dgnifasce a Mendellan ratio regregating into two clases. For with grouped data barring a fried total, the number of class (V) to which an atetrury value can be andgoed -Y-L This called the number of Depress of Preedom. Obviously two-cu llendella ratio completely described by stating the total number of individuals, and that ouring in ono cum Supporo Ho collect 100 instances in which a chancter le segregating amoog to offspring of parents both of whom m of the dominant phenotype, and wo And that to belong to the dominant dan und 80 to the recitare. Doo this dlater galtcently from : 3:1 natt The standard error calculated at ✓ 70 x 23/100-4-43 The departure from expectation (of eltber dan) b & Thl, belog well under twice the standard error fires no ground for numing that wo un dealing with other than . Dorinal 3:1 ratio This method is inapplicable to ration of more than two dames, the dgnliounce of which mast be tested by means of tho z' datribution (Tuber 1941). Furthermore, in human Penetbo particularly regregating nation are often made up of 1 Dumber of emplo, some of which may be obtained in womewhat differing circumstances. It is highly important to determine if there all accord with one another or if they are heterogeoeous, in which the they must not be pooled to provide a total. Tbo x detribution providos, lo addition, test doch beterogeneity and this should always bo applied In puch instance (Keo Hather 1438) It wu explained to Chapter I that the crow-over room (COV) I obtained by adding together the two cromover dums and aprending there us porcentage of the total. Consequently the standard cirur fa peronten ben appro priate tort of ita Nyobades, ed should be comployed for this perpors" may tako tho ample already studied (pp. 23-7), that of Doanel cost-colour domioant to alblog, and white fat dominant to yelor fat, to the nobbat. The ·16 GEXITIOI TOL MEDICAL STUDIYTI to explało tho procedure for doing to The ruluo of Auch work will, it ha bopod, now bo pparent An nccount of Inkage and crongoro wu piven in Chapter L and it wu pointed out on pp. 94, that ouunto information on three geastons is normally required in order to study these phenomen. This is rarely inulleblo in human material, so that it is important to realize that link 40 data can now be obtained from an anelynis of two generations or even a coglo one. Methods for studying linkego aung two generations only hero been developed by . number of worken, and now provide forly accurato monds for its detection in Van. A ducansion of them is outside the xcope of this book but an admirablo scoount of the abject Li given by Finney (1940-1). A lo senative, but untul, test for Inkaro may bo obtatned from a single generation. It reqafres indeed a somewhat atendivo study of brother and deters, but it is far more practicable to score two or three hundred individual belonging to a dnglo generation for tho dat button of two contrusted character than to do so on maller number belonging to three datinct generation. The method of obtaining Inkage data from tho cumination of a doglo generation is doo to Ponroe (1985). I regard it as an advanced great potential troportanco for human genetic Tho proceduro is not dificult, od may briefly bo conoderad. Two children from the momo parents are desfile for stren chance for instance the presence of applutenogen A In tho rod blood corpusola Thoro aliko in other respect (both with or both without A) are placed in one can, whilo unliko pain (ano with and coo without A) ero placed in another die Thoy urother similarly candied for any other uni- Lectoral chancter This is repeated for u many pairs of pibe (that l children of the same parents tortopecure of K) u posibila If the genes controlling the two sets of contruted characto uro unlinked, the form classes will appear in dopo proportion. If, bomover they are linked, the two cases representing pain which are alle unhko la bout respecto vil bo in aces. The expectation on the costumption that ·NITIODI OT ITODY 19 Antigo does not occur is obtained by the proportions of each con trosted separately Ao complo will make the method court Prevence of the cool platinagoo A unt Pruenos or shoes ofred beb 40 (63) 17 (10) ul. 0 (1) (1) 40 30 00 Table F Cherbaation of two aberto for the dotoction of Kalap. The valoon to brushoto an thou spooted on the ampton dlfr ortmoet In Tablo P modified from Penron (1985), 60 pan of wba uro woored to the protenco or abutocool rod hair and for the prononoo or absence of glutinogen A in the blood. The nombeni arpected on the sumption of treo mortucat are entered in brackets below the actual numbers In auch cam. There expectations are obtained by dividing the total burber (37) of de who are both atiko in respect of hats colour (whether both red or both non-red) lo tho proportion in which the liko wod uplo blood-poop class aro db tributed (that is, 400) Y thu obtain an opectation of 88 10 Similarly for the unlike pain for bar-colour Theme total 8 and, when dlatributed in a ratio of 10 7 giren expected distribution of sil Naturally tho proportion could oqually well hero been obtained by dividing the blood. groep word proportboostely to the hur-cobur case. The data demonstrate tight arce of een patru (both allo or both onllo), u follow trea palo odd pain Tou! obrerrod 17 00 apectod 60 ·150 QENETICS YOL YEDICAL STUDIYTI The dgnificance of tho result can be established by calculat ing the standard tror of the proporbon, in tho mana indicated m tho lost section. In this mtance, the standard curora 87 It is bowever prefabbo to ove the r' ditabtion (Fbber 1041) for this tort of monificanoc. The departure from cipectation is of the kind to be entid pated it inlage occurs, but it not agnificent Yet larger numbers might posibly demonstrate linkage between theo genes The method of the widest application. By its inc, information on homan linkago could readily be amazed. Attention must be directed to an error which seems to be nather widapread in the interpretation of linkage. It is often noticed that to distinct chanceri ero inberited together und I havo repeatedly found this attnbuted to Ankage between the two genas controlling them. It must bo clearly understood that, I the population as a whole, Ink ugo CD Dover produce such repult. Croang-ove will wwwly reparto linked genes from ono another mother frequently For the cross-over value is tually over 1 pa ocnt and even in exceptional instances of very rare uolang ove this procens may bo espected to occur at a level will above tho mutation rate. In the general population, therofors, linked genes are just us often found democlutad u como bloed, and linkage provdo no explanation at all for the Inbentance of two chancters together Such result aan bo produced by linkage only within gren fastle It is then doo to the check imposed upon tree soortenent by the presenco ołtwo gena in tho ume chromosome but this bahipdru.co only not an absolute berger Indeed the tendency for two conditions to be located within the memo famly though they appear independently of 000 Another in the population uwbole, 1 dutinct lodication of linkere til uds soeption, the inbentanco together of two distinct characten Hattributable to the multiple effects of angle genes, a pbcoo- Denon which has already been dikmed (pp, TB-80).

·NETIODS OF STUDY LSI IL TTE DETECTION OF DITED CHALACOEU The rule of conreathe is the study of bereilty has already been descried (pp. 67-8). It wu pointed out that the corelation coefficient indsoutas the degree to which two vetables are wodatod, psch, for betanco, u helght and oyu-colour 1, on the other band, to mocation between the same character in different portions bestuurd the coordation coefisicat becomes both method for detecting Inhardtance and comparativo moumro of Ito futensity For the standard ctor of the difference between two correlation coeffi lenta aun of course be calculated, m that it can be dotermine whether the currence of puthcolar condition in 200 todividual i accompanied by to ooourrence in a relation more often than in a random uplo of the population. The methods of alculating the carrelation couident are given by Pibe (1041). I a character to duo to the operation of soveral goue, ita wegrepation becarna todetectablo even when the numbet be quito all (pp. 20-12 Had the method of correla ticom largely oporredor that of aperimental breedinc bat In an organize auch w lan, in which apertinents cannot be wdertekess, cordatoo studies must be applied yet mor widely It pertcularly to bo noticod that they are upplloable to all charactent apable of mountment of whatever Hal. They therefore provide a tout of the tobortacon of mental and moral qualiber, in so far us thome and boomed qostitatively Partons othe type of dumerioul compartoon ro umulable for the purpose Tho Delaurement of intelligace s dl courns a matter of much dlliculty but the cardully derimod Binot putem Kettu to provido . {ut bade for anticouting Inborn abbty In childres, totally hospoblou I believe it to be of appllom top to bottual adulta It is adjusted that cavironmental and temperamental deeds are largely ecluded, wo that tho Tuolta obtained by Itsen nithe Deadly proportions to the potential apacity of the children pumped. They are exproved a number oled the Island Quatlon (LQ) ·102 OLXITICS Yol MEDICAL STUDENTI A valuable ontmple of its who in genetic provided by Fraser Roberts (1010 PP. 87-8). A group of 8,400 children al school 490 wao gtren mental tests and cardile u Bright (LQ >119), Arango (LQ-91-113), and Dal (LQ <01). Throo dames were then relected, compriding the brightest per cent, the central i per cent, and the dullet & per ornt. Tho mibe of school age of the children of the three groups woro abo tested. It wu found that per cent of the aby of the brightest children were belght, and only one per ocht ware dulls whilo only 8-7 per cent of the abs of the dullest children wat bright, and 80-9 pa cent of them Tero dall Soch stadios a there hero clearly demonstrated that inheritance plays an aportant part in the development of mental character Analyus o murober of them rugrat that perhaps 75 per cent of the mariation in fundamental intelligence is genetic. It must of course bo appreciatod that the war 427 Zodirxdur? rubrequently makes of his mental aodowonents is largely environmental, and quito outn de tho scope of exch torth It is undoubtedly true also that there to rent variation la the rate of dovelopment of intellectuel, u of physical quehties. Correquently children of apparently Dodiocro aspadty may occasionally attain to high ability whilo many clever children do not fulm ther carly promiec. Environment must be an important factor in such changes but the daterco of genes controlling nta of development and the time of onset of process in the body (pp. 091) indicates that heredity is also in part rospondbilo for them The hereditary component to the control of Intelligence ! particularly important insamoch u mating for from being at random to respect of mental quahtles. There is a strong tendency for the more and the low intelligent Ixembous al the community rapectively to marry those who produto to their own mental levd. In rental, there an be no doubt that ordinary mental qualities are controlled by Dormel genetlo mans, bong determined fantly by beredity and environment, as are phgral cancta So too uro prch conditions u teodendo ·180 KETRODI OT STUDY to be od nancy a fact well demounted by the nd Ilbette (1933) The body of twlos play an important part in the detoothon al laberited conditions in Han. Two types of two ezket, fraternal and Identical, and the tendency to produco * or the other of them to inherited Fraternal twlos sro dac to the dmultaneous ovulation of two con both of which fatithood. They may thereforo bo ether emler or do smer in mers, and they uro no moro clandy related to ono Another than ero ordinary brothers uod deter Identical tobox, on the other hand, wine from single fertilisod 28. which plita into two it an curly stero in development Therefore they must be of the memo pot and contain scootscu roa. The distinction between there two type ta wually H-wheat. Patorul twim dilter to many ropocts, whilo Hential twins are shoot indistinguibablo Hero od thero doubtful instances are found, but thorough cumination Il tuolly deeldo to which can they boloor this abould tenda u many physical fosture, known or procumed to be genotionlly coatrullad, u poble, aleo such plyntologloul olunate us the blood-proaps uod the tutto torte Tratamdal twins, though no more aboo goctially than ordinary brothco und dotaru, tend to live in a more dmlar anyironment than they Statistical todlas on the differences between ach twins and between normal dhe ero therdoro of tertia tn determining the effect of artrommeatal mariatou. For more troportant, boworer uro comparisons between the two cuxa of twine. The dilatoors betreca tho memben Hentical pain oro purely cavironmental, genetlo rule thon being wholly beent. They are of courro abject to & man dmilar anvironment then are baroul dibe, but not Oro than teatem two, so that they low : nther precbe mount of the timportance of environment in pro ductoy Tulation, whether physical or metal, and the Anterity of the beatsoul typo Indiaato how larp. part battributable to haradity Twin stodia en of warrion to other way, and those aro 10 ·184 INETICI 702 YIDICAL STUDIXTI well Ilhustrated by a seful comparison between the genetic of tuberculods and preutssonie, drama by Freser Roberto (1040) Ia sumber of trios bo studial, one of whom faller from tuberculosis, the frequency with which tho other member is also a tuberculosis patsent to much higher in the kentical than in the Internal type Herodity Is therefore important in determining rusceptibility to the bedillos, bat the environment i abo a lactor anco ona manber o. put of Identical twlos may sometimes be tubaculous when the other not. Burther in the latter circumstancos tho pros Doole of the divano a particularly hopeful ance, u Frunt Roberts points out, the wlected individual hus mocumbed In tpito of a high resistance. It is notoworthy also that tbo ste of the lesson i pertly determined by hereditary vencie, door thus far more often tho amo in pairs of Identical than of fraternal twins. These facts us to be contruted with the frequcdoy with which poeumonla aitoote pain of twin this I sourctly any bigbar la tho Identloul than in the Intanal type Clearly bcrodity not an important pent la prtdispoolng to that disease. When a syphilitio woman give birth to Antanal twine, It rotactic found that ons metaber only of them allan crom conreutal syphilte. This is strong evidence that onceptibility to it to be part due to the action of gener The occurrenco al commanguincous merrlagen provide Taluablo material for detecting muro receiro cood tioos la Kan. It bo propodtion of renal application that, with parttoolato inharitadce, interceding tedda to produce bodo tyronity Whoo sell letillation ocun, u la planta, the proportion of heterozygotes is actually halred at each frenation for those individuals already bomozygou remalo to white ball the oitspring of the beterozygotes uro bomo Tyrotes. Les con degrees of labreeding produce bomo wypodtynkeblon play but now the lo definitely It's individual la beterdaygote for some tiro recessivo autorou medition, the chances that has brother of Aster s beter pote unlil, they al 7that a ant coaria botales ·WITHOPI OT STUDY 185 The recir conditico tects on individual in 10,000, 1. percent of the population are beterosyrotos (p. 180), od ffove other marriam varelatod person the chanoes egalost bowite being beterozygous leo uro 1140 but they aro 1:7 It bo mama first coudo. In theo draumstances, the cence that the condition that appear among the odepong une force od kreatold by . Aut condo marriage. I wo ponaldo the population us whole, ono individual in any kebeterdayrote, so that no murluge in 1,500 ka apable a producing the bomorygon recento (which appende in con quarter of the offspringh, but on. Art-condo marriage In 400 eur a do: the frequency to on time focteurod Thame Lacta indlasto that nur moores must appear Andong tho ofispring of soutanguloods marriage for more often than lo the groenl population. The frequent cour redono conseculoty botwora the parents of the matterlay from .rar dloudlagportlogo of much foportadoc. It strongly ret that the condition biabaltod dmple rooowire In Pogland about do per coat of a manlagen take place betwoco first conding. Yet over so per conto bow madering from Japłonaria (p. 7) are the optepeling Brut-conda merdagaal thereby Froully it t nocenry to mention a fruitful moxdan od ator in the collection of genetlo date I. charnster is in autosonal docalmant hall tho children wbo bare odo ntleetod parent will on the arengo pop it. Bot me famille will vetalo too many siected individuals and others will contain Done. There in reality cance wach other out but to recording rich family groups, those without atiected individuals will be omitted This will make the copdition appeer to wyregate la cont of the expected equality Such in eifect is unimportant for rene haring botan you apreedom, pa to sppearano la cortalo Carlles of character to Approximately half the Individuals al second fro rescatou make its method of Inbaltasca obrou But for readincaricten tbt cortoepooding ator la malou ·180 QINLTICI TOE VIDIDAL STUDIITI unler Yery cotnmoon, the rest majonty of receres barn normal parent, while their expected famiy laddence only 118 Therefore many familia in which both partat are beterozygou will have to strechod children, and will be omitted to collecting data Tbo ayer frequency per atfected family will consequently bo much too high, and the 1 ucentorted by the fact that familia with mody Adiected members are more likely to be recorded than those with Law Thus it may unjurtzbably be doubted if the station In one of simpto unffectorial inheritanoc. Statthaul methodu, bowever ocht which help to reduen theho kourt of octor TY COOCNIO It was shown in the fint section of the chapter that the nos responsible for rery rare receed to conditions uro extremely widespread to the population. Furthamart, It will be recalled that most mutations are doudontageous ta ellect, and that unit rourablo character teod to become retesevo (Chapter 10 Very large gambers of much pedak mut therefore et lo Blat. Coorquently we can bo MITO that each individual will be beterotypou for some of them. It is for this reason that only cloro in breeding bs generally harmful, so that prohibitions against It exist in the law of most countles. There is nothing mysterious about the cleots of brotha wod dater managh, and la o Leally wound took one which carria few disadvantageous genes, they would pot havo unde nublo consequence Thets danger amply due to the derulation already made that Inbreeding toode to product homozygooty with lot conscquent reproration of didvantacou recadra These facts todicate bow diialt must be soy erteiro Programme of care la reform. It is absolutely loopowiblo to nd population of ditesto inbenta un simple recente Obrionly this appot be done by prercating a bo potter from it from baring children, becaur the betarongoten art landstinguishable. But even if they could be detected, the pas vould be o ddy spread that its extermination would e out of the question Nor is the Atuatios u al umple in ·Mlected pero WITHODS OT STUDY 187 rapect of the beterosypou conditions (tho naled dommanta). These could be eliminated by this man in . dngle gamtoo, but only in one group of Instances to It ruth attempting to do this, or nther to love their inddenco by pretenting the procreation de leut proportion of From the point of vier dagendos heterozygous delecta must be grouped into two cases thom which reduce gaitantly the number a children born to atooted indi Hatuals, and those which do not. The flot of these, of wbich Durla's Dlcun is an amps, could never bo diminlahod materially in the population by curedio methods, beowuro the genes controling them must be distributed with u frequency not greatly above their mutation-rata Conra quently any one of them would soon bo established again & Its former loved even after its comploto elimination. The econd group of heterozygou delecta, there which bero but ght influence the number of children born, procent. Lagltimato Beld for the application of cugenio MolITO. IL Inclodas open lew sovero dhouses, being tbomo whor Ort ymptoms appear after the average 4 of reproduction, of thone Hantingtoo. Chores an instance. However L Darwin (1990) had strehod that the most valuable opportunities for eugenkes are provided by mult! factocal conditions, while notually allor of more rupla colectivo Improvement Mental deficiency is usually of this 7p, though It may also bo unllectorial It of grout Importance, afecting us it does about 1 per cent of tho population, while it tenda to increure, nather than to decreu the mumber of children bore. It is oertainly true that . progamtos of stribution could materially reduce its cace. Of J inberita oril, Insanity presents Dot only con of the most proming but oon of the most dificult problems Paltary to damage the working of a deliately balanced putem like the human brain in variety of way. Thus it comes aboat that many Hicret rere may en product apparently similar forms of mental decot Only be und ·188 OLXETICI YOL MEDICAL STUDEXTI there, when one of them chance to pre stato porno recognis bilo dalbopal chancter can tho imllectorial nature of typo of tatal deficiency be detected, u la cpilots or phenylketoourie It must not be supposed, however that no adesco o. eugenio nature as dy bo giran Indeed auch advico has already been offered on a number of occasions to this book. Those who belong to family in which a linked dironda oocure will now know what type of datboy run a marriage. Those who water from a defect inberito usa plmplo dominant must realize that they will tranenit tho gedo responsable for it to ball their children. to certain instances they may well question wbetha they ought to produce otpring It All particularly important that those who belong to a family in which dangerous roceadro dlecand bus appeared about not marry a bear relation. To abstain from so doing i 80 crident duty be raron for this will now bo dour and it will be deur also bow greatly linkage studies will belp those wbo are fuced with such perronal problemos u theme. Wo baro to been oosimpled with Degatiro eugenios' the climination of diadnuntpcous chercters. There artists also the question of poedtivo angeloa the disemination of adruptageous ara. Among animals och proceu i quta practicable, and it has been mocemully applied. Clomit inbreeding, brother and data mating for cumple, not only aura the regregation of diadnuntagcou receniva bat, it combined with the elimination of the unit, purge tbe muco of them. By content repetinon of this process to two hoc, natha invariablo stoclu can bo bult up each cotaning relatively few harmful rena A anglo out-croes' betwoch tham enpiros much grepation and a wide range of wration, from which the best arning an bochote und maintained safely by inbreeding Sach proceduro obriously loapplicable to lan. Moreover wo bare et portent exch poor cnteria for deadling bat buman types are drastatou. Some of u buna mcoupletd the conjunction of weakly body and met lain, sod vout all familiar with its depitsong cover ·LETRODI OT STUDY 1 Lat to human judgment, It certain that the gealas would often derer bare been born on a minor auly, clover men should seek in marriage a partner wborn mental powes ut food, for wo have seen that, on the average, they will prodaco intelligent children: but so aateadre prognummo of positivo eugenics a one for the distant future. The questioo o etagenio reform encroacha opon one of the special preserve of the fanatis, the problem of Race To sono in these days, it hus become a creed that much coo cept us the Batush, the Nordk, or the Jewbb races here, « bare not, reality In this matter u in many others, extremo vlom appar to be incorreet. On the one band, it is not edmable to malntain that auch ructuure purely artifcial. Their cbarston have some reshty and wo baro good orldence that they may be preserved when do people is immersed among other. It has already beon mentioned that the blood froap frequences of Dutoh od Ruslan Jows are much moro altko tban are those of the communities among bom they live (p. 107). On the other hand particulato inheritance allom tho mulntcondco within auch too of Tutoerres of nariability apablo of producing without ncal mlituro, far groter diversity than that repantog ny of them. Recurtat mutation allow tho fona o ono nuce to appear to other, and great a part of their reno-complex bare even the most diverse of the human rico la compon, that do sbadow of speciae detraction an bo detected area between the mout dansimilar of them (p. 81) Tbo proportion of revetlo outerial which is different In the moro nearly alled rucos annot be great An acourte bads for the race-concept, is so far as this to attainable, should reflect the time anailable for the accumu Lation of genetic diversity It might be reasonable to crot for stample, that Eaptisbonen had half their ancestors to common Afty generatbou 40, and that should hart to po back seventy-Ar reportion before thb wu true of both Engllohmen nod Prochmen. It is probable that the most redoto of the race arc, judged from this point of the many tlma older ·110 ORXETICTOD NEDIDAL STUDENTS Tho Detbods morested in this chapters provide the nam for incitasng rapidly our knowledge of human heredity Additional data rather than de techniques are at parent tha chet need. I hope that some medial practitioners wil tee that it is worth while to devoto time and trouble to obtaining auch information. It is my bellel that it can bo wed for the beseft of mankind.

·APPENDIX I CYTOLOGY CTTOLOOY II the study of structors, wd I bero no ter bod that the reader por michakoonloo oftt ta por un roquired by medical students to any Antibelt Other. It may be bort that some bo bare boecquentano the object may be to read the book. Furthermore, groot moon ban bere nede la rocket cytolog during the wat treaty rats Thon wo apost that the information o putto, and capetely madlock, bo pomentet out of date, may pomaly down to morbo t I born therefore propered thla behal romy of the telenot poots of cytology AD wbo toquin om detelind scorent boold arwalt the fundamental work of Durthington (1077) Ialo wlab to roommend the aculeat Mittle true by Volt (1037) ( ) TB TOTUTU STADE To Arte mahatang at the body s olled protoplann, and the startowy Gridad tato plorocopter unite ale coll. Rect bol boscowpowd of two parts, a mucho Wblete control the motivity and the nato protoplaers, alled gruplar The protoplasco of the comis, kovo M Mulaples, odomd la aud OD Thon goe by outtiptention of the online, Dot by me Low to call The podca cute to the chocowe, and how cauty the bereditary touto o pow (Compte n. Therefore the matter of the word important that the brotowo should be no debuted a col diybko that much of tho to Le foto stuleb the old on puitte booll para completo e of the Northe socle dividon Laulled tubes. A widet hot doriting wd to be in the teethg degesdoo it may theo bb date of paydolopkel settroy the tem 4 anfortunata De bruto ply though not quite alway bulbo be the rette mole when she was only led by the that is to y Hong the vithe Date Udartiempo to od boy this with to what colour ther parte din Owing apporootly to the high water A bud Alo the boat, berme en tabulk don tant 11 ·140 OLXLTICS TOL NEDIOAL STODETTI The methods morated in this chapter provide the meani for increasing rapidly our knowledge of bumuo baddity Additional data rather than des techniques tout prescat the chle need. I hope that some medical practitioners wil feel that it is worth whilo to de rote time and trouble to obtaining rich information. It is my bellel that it can be used for the benefit of mankind.

·APPIIDII I 159 monk, aled the catrodo, les outilda tho noclear membrane. At bo od of the prophen, the two parts separate and moto to opposto dos of the nocicus They malo la copedas, bom by s molbod regloo of cytoplasma allod the 'stadhe At the beloning of the prometaphase, the mockar membrana dilim pe and the spindle Hobs Lende uot loads couple in between the to contram Each chroonam thaa arpobrom the Doctor ploto delitonal pode coments whileta con los round the one plade, toetudag is bulk. As foly med therefore, the platio le composed of two dlatinct parte structura called uplados Abro rooning from the chromosome to woch pole, men formerly donorlbod. Indood I wore wated thet by their contraction the two chromatida muhtoolly poled sport. It Low mown that do noch Abrw oht Wb oppuret, they are probably done to the shitukogo of the podio duty fretboa, ang crich to appear betwore ita pantaly arud o comports. Aldapan. At this iter, the chronomes the on the equator potem whow poles are the contropomor, and they sco welchor to the podle there. That is to my thoy en poated with tho pertpheral spindle elements of nochr odgto what they Leme themelvor organised. It come that they never come into relation with the control plads formed of atau Docteur material which, to test, dow Dot arket in all bort. The stuhneet of the cromomocou to the spindle mocurod only ethods both Attachments, and their bag um stretch out into the cytoplasma Lauromovom brombo tato tro parte, ooly that containing the podle attachmeat become anchored to the podle, the other portboa dosta eww and bout when the old divide The two chromatiche forming woh chromoo Bere comer together to the metapher than to the propheus Coperqoratly the pot spurting them no longer permet corpt to trang Yeow motion, when the churomono wae the shape of Ogu. at dght Bpoole methode show that the chromathie hare tho born of tabtly spied petog witho thla pellicola. At the time, tutto e Domy to contact, but they can be punind bothy from one mother to reting the chromatid structure The pain of doometido codied buchependently footbar. The pin troetine derelope dutag late prophes width prometaph It peeta for the female of Dxod and hen there the star bort, oue rello al # may will be Volblout the bagtomkog the set propter ·OLXETICO TOR WEDICAL #TODOXTI Axaphone. The metaphase be a period during which y BHL chusgo Oooun. tatty #kot sort duration The como azapham te kod by the situat auch podhe attachment into two parts. There the reped one anchet o that the two chrottle forming much chrotom u drugod apart to opposto dictions towards the pol of the pindho. Tazam the peopbass chromato booome the anapbase agitar chromom somes When the two other more to stance from Another ther wpanatoa ta completed by change in the cour tartu regloa of the place. The congue forontar a manlled um body which petube the two metu olcamphtar chromosoma not larther a partir Telapukan. When the two groups of darghter chrono 1*** *puntod wildly they come to rest is undergo a casa change the Interno od than wilab took place is the propisano A mucous membrane box, the chromowme taka la watat moll, od to increasingly disticult to fx mod to Fiordly thayan no longer be demonstrated by the moun. The muscow bu the named to the moutag stage Kather during luto anupam or telepben, the cytoplastic Atricte between the two beply formet social, which aro who coclomod with a parto cella Ench of them theretons pour * oot taketa met od odlichoul chromosomal There acatain the full completion of retrou, kaco they want produced by the loopt todlami ilizing or chromonts whilars had grown to combine tbar or thicknam. It will be remembered that the occurred during the previous routing suge Mitowa la Dot completo, and Ebe Dew dezghter chromowca wtb themely grow ootd they so wit foto chromatica sbortly before the set och dithalom (m) MOLL Det the formation of the pmcle, no totorctang of material ako place between the paternalty cod zatarrody dorty berabers of the pulo of bookigas chromo, renulting in porta crowngu wbitio the chrononne amber redwood to the diploki (20) to the haplok (o) Tbwagtut about by ipocal prooo called meloun It combate of two highly moodle Di dhidod, bepy tbo lut which the permet undesgo Weio de datoed by Darlington is to dirbtota of the posts with bot o diralod of the throno Tu # boonpetence In watk dtelefon and . And writte diolin. There ·APPEXDII I 16 los bolety be deathed Tbom heterys, much a podle toto tas, stubhtbo po to common with metoda v beorolter (.) TW hr scoti teision Propken The prople of the top thelotto direton babool and cooplo. It mabilised tuto four perts, the Leptothor, 80 tos, peytons, uod diplotno stages Laprene ** The chromosom presy longthin thered while no pot je pet bato Chrome, they would best the beginning mitotie propban A hes of detty Welky pamia, whom position to constant for promotoromano bo bo datooted along the weath. There are and dre. It happoned that they may rupture the greater hom west Tbo borobopou ohrown coton together be polis. The se do to odtion betwood Wheetboel otromo miro It does not rwalt tmn an attraction betrouwbare Sotto, Bur the remain nopubad in the region of N London (AOL ANA ODOHC Don of the perbere the beplota ber(of double bodies, allod Holm, komad. The borm.pl woofthed length, and thoy thertor mnohrombie the chronorm of mitotilo prophen The Dact that they po two plade tohtonte bomen todistus that rey antot aton Packy eye Tha come the pooled duty which the bomologoun chrotom i uroctoled u branite. It may et hors coulerable time. At the membo of och bitralot - poble, but they won twist round on mother Durtong pachytone, the chromosomo politt foto barometida. Asarwady explamod, try Dortowy do betonow-draco starta bat the A moda ta powodors, for the rooting sp prwooding # short or tocompleto. Cornequently the order an Dot tedy to dlake until the prophed sond Displaku keys. It was thet thekruhlat betrap about ood Desting Shropatring to do the area that We beep topther the two durometida comuning cech bromo during the ottoto crophens This to attraotte of bonsore site in para Bat word ETOROM do logo atest on noodber etter they pet ta pestyle, for the trotoo trukod to the pain of chromat de o posky thom Lodeed the chromon that the led to ori ·148 GXXKTIOA YOR YEDICAL STUDIXT# nput oning to pro sepulka Bowmer they en pored troca boli to completely because they bell together a outala ponta were they havo baterchanged material. The tot authod chance, and the formation must behely be donethod. The four chromatida forthing the two chrome of bomo lopou pelr allod a letrad. Iro o tem, dentro repactirely from the discreet metabers of the past, ay interchange mutaha? a potot, while the other two remata Lalakt Tubs Interbang of Puterial prodooo pooseblo cung orer Sharon it ha pot scoop pansed by an interchange of partners two of the car chromatid runt mo. Oror aos mother lo the form of an X, where the DADO blog (F110). At least one cha sasly any CRU bet dy pair of chratacenes, end to areago saber PE 20 Can formation - hegle chant les formed beds pats of bongolog chrowoom. Tot ar mo compooed of two chromatids bulab an wanted at the gooche anchment, bere reported iod A on d. It w be to that the chick laratra two okromatidy dertred from different banalogous cto uomone walch interchange material but not pertinera palat, while the other two al binct may uvod bo w bigb weight lommer thoy do not acetur rury pour together because the chuomaths are still court to rest how twing TTA OCEWTEDP of an chhane therefore prontato the formation of another in the impediato paghbourhood Larodon toy the wae chromatth. Consequently doubin croesoforo do not take place betwee gone with the near to on koother where the poenomenon of otorlerotico (o Complete sytomeghoal proof bas now been obtained that the diromstkie do not rely twhat are one another bent á at forts, but that they actually interchango material at that potat (vor During tor, 2037). Volthet chlapra fortsaloo could do provide the physie basis of poetlo odore After the chibanata bar Logo, the crooneths worla d thickene la mitous, and they torno through about 180 deprem Generally who the white channata (the points at while the chromis pas cher com esothor to form a tend to Lake any from the place attachment torudt ose eads of the ·APPIXDII I 147 chromosoma. This is allod xndition. Obroadly I doo et Moot the attuation of the Interchangodamente, but merely the podtion of the tri rakalting from that later hann The propeo de Colored by study normal prometaph replan The Twomble the metapbed. mito It w barmhede borror that auch beboat (ton) por two podle attachment, o patermly od 09 maternally desired Araplos The plodhe attamento do not now dirlois, as they do ta puttade hen, therefore, thom of bomologous obroponom begle to ropol.com other they dog part pala of chromatike Consequent upon chisma formation, the coutain nootloos both of petoral and of maternal origlo. Both la mitods and in the int meloete, tbe dipbold Dombor of bodian more from the oquator towards oust pole lappbar. Iı altock, thom in the diplokd mumber of individed chucomo Roses, bot in the first prekid they won the hepbold comber of cturonowomo dirkdled Into pan of chromatide (whlah on yot ball together at the plodhe attachment). The ropertion of the duro owoce mote and their monument towards the power of the stoche de brought about u la mitor Tulopka The doo pot dine materially from normal mito de todo pber. It may or may not be callond by bolo moting stage called on the phone. (5) TW co wlasi If there be bora no interpus . nood malo the prophane te not moded, and the telopbew of the Ant medotto di ridoa pew directly into the procetapher of the mood. The COLONTOON at un totorpher Deowultatoa woood peodo propter bat there to Dort woda po try pomnorthy toature. Predahan This dutes from that of a mitolo to two repou anly The crocoma un of the baptold wombe while the cromat into wblod och pet me only held together by the wa attentional darhere they dr dey ·OXXX71C3 TOR XIDICAL STUDENTS Tpo motaphas, anaphan, and beloping and for no poll comment it will readily be approchetat that they wait to their productka o puncte sootalning the baptad mumber of dyldod chromokoma. (c) Geron muy o wload In general, It may be mld that relate coasts of two bhilly abnormal olayleoas, modited from the mediotlo plan. That erolution bue kergely been drpecadent upos na altratta la uning much that the chromosomes do bot pit into chipuakta aotll the Art propboxa well advanced. The tarotulbule for chromosome pairing (148) Mekaallowa na interchange of material to take place betwo bezolopou chromosomes, and therefore tampoonide for pooth croning over It also reduces the chrokome puntes from the dlpkokul to the baptabel. Formerly it was bed that seboude coco prh a doghe rolactina diretoa (the art belona) and that the la followed by * nitonta (wakte oorromponds to the moond nakoube Bucbo vlow ls totally Loncorrect. The memo for the male razy chemrly tho fundamental dátlaction between mall and moclock and there one worta barter cooldertoo. Toe and the function of sucioar dvisloa b genetle. A mtonia en quating divlaka one which cogans that the Vangtua elle wall auch receive the Mc Rumber of goa Llant porod try the from which they were desired. Wiesol bocizno i battan about Woodeta regration if no carta were to forta, the whole of wegregation would bo ettected at the ant moloch, to that tho micosodtoy dlrheioa (the moond mootouchant would be perely equating and therefore puttade to typu Online to chu Lormation, bonore greaton takes plan the Art or the second melota alternately w mo pass from our later changed moueat to the nort, starting throm the handse Attweb Let the best coluitbalam before the ruta an tomond therefore fummos copotried lo epeting Mandolima were too us to the penultimate on Thurma la moand more pot mitati ·APPENDIX II CLASSIFIED LIST OF SOUB INHERITED CHARACTERS IN MAN TIIN LIIT b. Amited to cooditboos urrained on tality good whilemon to bo determined at least petoetpally by Anglo malo pron. It be pot intooded to be complets, and lo fact I azotado raumber of centers mowa or promed to be unifotortel mucoation on there may bo obtatood from the worla sted to the Bubiography) In dit boe, milfactorial faheritance b been stodhad ataustvoly to Ven, but thorolta annot mo unfoly bo mummod in tabaler form The caructen en oranged to groupes detingahod by botter Withto ouch of thow they en pisood to apbabetlool order and numbered. This allow crow-roaspoon to be gtron when dmlar section produced by Hiderat port Caution must be robod to ung thus Bist. In mome kretanom, ovironmental que muy modify the promou ofron Pather coochoo whom genetia in charty estab who may sometime be borttod tam correptional way Thile cay be du to the ordinary gone opening to make gene-comples, ar to the notion os distinct pon bertug soportionally dmlar atoote Per ample, though wbudem man knowo to be recording domestibileum has been reported a groet nartty Arabandy aqlalood ( 17), Do oviscon cdote that the majority of the O autod Homtomat' chemoteo to man in prodaood by ra beyting houthal Onete ta the barstonyro and bonosyrous Abbreviatioon on cord to pre farther information on thore suncto which ma parthouderty robjot to various trregulartilen thlon Probabły oplontoos P Dowodooel heterosy po mesiatlon Ooondocally pot aprend la heterocypte 1 - Docatnapon peoplete • Expression verhadly redelike - ·10 EXETIOI TOR MEDICAL STUDIXT A. SIMPLE IORITE L. Ular IL Lannoo Hooo-Bed at 1 saptooarte dromo & ineurodo Wogy labo LL Apollon of HL 18. phooy Partout amrollo dlouy furot. 14 phonylthbour, booty & atbero. (BO) to tacto blow or my yo (4 16. polydactyly (13 ou dat-outh It porphyitaarla coppia Taur-Lobo hercat IT rod but & Friedrichstad I redolthe permetton, with . bero-tp aod cat polato dana 18. RO mortloo a sotto 10. tbthgodt og godta A od B. 1 JIX LA DOMINANTI 1 AB blood-group de n. bactrophet 1. seholurlo Jandle. Huntfoyton oboru 1acboodtoplastia drarry Ichthyoda mugurta (yle 2. Allergy ( 8 COD) (D1) a anddrotts actodermal &gt 24 otacz, alacana od pbede (D1). He faundlen, scholarla plus cuti cogantta. 24 karatodermi & theretoa (T) (AS) 20. Dout into inforto, D 0. auditory dem atrophy astram today 7 bono fragtity and blue 21 Detrodbrogato ceutian 2. niyot banda * bachydactyly to. Dedem, noflooctorate 9 aanttia praemator. (Doulanglah 10. starct, congenital 1. Over dhon 1L cholesteroes outh 31 phalangeel synortosa 12 golobocon Iridi * pikebalding ja Dulr'ı dhan. u polydestyty (t(AUS) 1 footincham of tacth 1 porotantos (coor 1K dlabete boupido (TL fooddotont. 10 epidermoly, lopta He permeture baktas 17 spowołytymal dyt tropblos TL throcter polypl 1. epilat ( 3. rethet plupoenton, with Il epithellone, bool goitia out doute (DA FA) 20. gamot. ( TK 11. Notre ·ULIDIY IT 151 * mbeccoor cynta, multiple 41. white forclock (B-49) #glutis peapleghe (FS). white forebok (tortioned # put tot to maba), (B-11) torth, operuary 4 Woolly befrit 40. tylode palmas et plus Potre tada (T) INTERVED ATI IJTI OITOOTE: Lady streghet, mary haft minor bachydactyly (Europe) LUN Wood-group. D JEI LINKED NICIUSIVES 1. en drotlo cotodecom dyr 3. fo.complete albintum pharl's (ba). macol tota, sboca al. 1 coloar bildca, ned groen 7 mlorophthalmia (1 family) optheberro atrophy boradi Ibum philis (1 lobo orpha petialul pigmentos with kohthyoels vulpuis (B) out dentno (B3, 74). 1 IXI LOOD DOMINANTE 1 mletong taction (1 bumily) i nystagmumu (only about so ca per bot brtarodyrom a prodae) ( T PA TAL MIXL XC OX 1 epidempoty, mren dyr A poto panpleghe, twoudno tropbilo (root tre) (um 2. barelp and cloft palate o total colour blindo (ro- (ruotra) (AO 4. Oguobu's dlou ( re 1 veroderme petoro rodottle plazmontor, with- (rodrom out detalles morphy, i dominant, i retro) (BUS, DO) . TO L » XK QE IN Y 1 kohthyol lystes go for 1 tabbed too (i form) ·APPENDIX 111 THIS Alb GROUP (Continued from p. 114) IMPORTANT INFORMATIOs on the Rh group ber boots obtained Loote book was first pabilal Asttpot yet anlab ATT in olgtaal papers, and a tettel trattat cay now be bad apoo the monetle sodio, I have decided to pro add omny of outain parts of this work to ao Appardos (tor tuler detall * Thylac, 1011). Hacroalyties of the tw-bow most womonly meatba that clerin gris Donatorum It aloo prodova vome of the -births country star the twenty cytoth week, though it to dore to rold in pregnancla ding water Tho Ahtatta only prodwood La Rb Degatire ladridole ID then It Day appear us toolt of tourtoina by Rh podth blood, or al pregnancy in which the foetal blood is Rh powthre, that conditia batning lobedited from the batha. In the marriage to light the husband Rh podtiro and the wife Rh negathre. Float-bom ob reo way aroupo hacmolytlo do, and then may bo wt torto birthy botom o cotod hud ppoan, tar tho Hh antibody can ruoan for you in the outernal blood mood Lo scomata from soveru prognende. If the busband # batetusyon for the game, Janata birth will on the artig ba Patrol Utrolyte symptoma tundly occur galom the botaod bamo FU. Mthroo out of soroa Ak pouttre en v bu do cient Bh antibody ha sido torted whicus bell the propunches aro Ilh negaliro Cosequently parents abould under Hand that we can stilected child bes yppeared, the chama of bearing houlthy bodno sguin is remoto. Appropriato trous batt, bom piros pood results Problastoary stope should be taken during the wobquant prof Do sad, peanution, this would also be done werner bubuod la Rh poutin und here Ilh pegura, aspectely the bara beto a births Tola bould constat tawarty that # Rpply of Q, The Deathe blood barulable at With Or that by any dgn of tocmolytic dise, the child should too be tror td with rock blood into reds, tot 4 erythrocyte bell 4,000,000 b radiod. To prostdo this, together itb = OUTS, boat 230 DC Mll be it aind, to furtba tartaloa y be needed the sold apply sythrocytas until the nottbody is the I'm stod un word that bigbly electory i Tasta, L. (1944) Britis Descopeda y United toppscot A.

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(1934) Lioy Orperion, Oxford Timofte Bewoniky NW (1994) The experimental Pro dootloa of Mutattoo Bal Ba, 1 411-57 GELAPTER IV ACTION ud m Tord, E P (1050, A Bite) Vanda Erol (sce Goldwell, i (100) stymistapiced Comercios, hot bork ·OEXITICI YOX XEDICAL ITODEXT3 ACTIOK IL Haber R (180) TW Garctical Thery hotus Schection, Orfoed ALOTPON IT Roberts JA. Fru.seri (1960) A lxtroduction to studio Genta, Odlund CRAFTRY Yard, & B. (1953) Polymorphlo od Thumbodmy" hat The Na Systemsla, Oword. When AS (1938, od Edn. Blood Crope and Blood Tray/ution, London OTAPTIR VL NON L. Pahor i A. (1941, sh Kan.) Statistic declade for Raud Yorks, Edinburyte Mathet K(10 The Name of Lintage Ich Lando ACTION TIL Roberta, J A Frazer (1910) 4s Improduction to Medlem Gorich, Otord. NOCTION TY Faber, R Aus(760) 7 Genethal Theorya Nam Schacha (sco Cuapter VIII to XI, Oxford APPENDIT L Dedingtos, C D.: (167 bod Edda.) Broaw Adoma Cytology London White, LJD (2037) Tu romo, London APIDU II. Beur R. 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XIDICAL STUDXXN Dalton Dit wapid ST 4, 10 Grow, 1, 14 Filter 87 draumu Daybeden mootty note 7 Diploma 10 subnas, TBT Deporn, 143 dupedranken at Dortmund, 17. 041603 dices Dominator buditonton & Grote 16 haran, Domo, 10, 11, 11, KS 117- modulytec 776 Dronesia, 24, 87, 8, 15 motip decide to 40, 180 Duhtmega 34, 1-7 Tout Dhanth $$ uz , # Exam,, 00 Debondoc, podlabowy w art. 71, * Genotype Lanban, 360 Quoco, ico Badh, **, DS ERRA, 13 (loodrich, 15 Ernu, 85 Endocrine ano, Gruneber Genipa 2-2, Romant exhiu do Other 73 tercih Centrum kateral, 0-3 opter, SL Gypal 207 177 toute you balco, 0, Tb 1801 och 76, - IM, 150 brand, o petalow nuk, Rannonia, 151 palloween, but, 250 AUTO antny dlymbian, Tu, 14 paula Erythro salonu BLAN, 13% portation in Ataula, 14-40 HAL 11-11, 12, 120, 120 Irabution, $T 9, 97 WYY da, uz Expresy 6 woofty #1, 133 Xrolor, -1, 220 wanata, Boo, RTK Hey, 11 Toon ( Go! Hohentuelle railoc, IO Eat up AA, 160-3 rontloc, 10 Nay Lett , 12 Idd, teen, 10 Tz Ahlation 10 Herecky buena, 017-4 moment in perioa 10 met na Toplarke, 4 1,566-7, 71, A, H. 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