Transcription of DETERMINING A GENETIC DISTANCE
1 LlncferstandlngInheritanceDETERMININGAGE NETICDISTANCE~ sworkonfruitflies, :adomi-nantalleleBthatspecifieswild-type wingsand{3recessiveallelebthatspecifiesv es-tigial(veryshort) (andthereforehasredeyesandnor-malwings)a ndamalefruitflythatisho-mozygousforbothr ecessivetraitvariants(andthereforehaspur pleeyesandvestigialwings).Furthermore, ,a,B,andbonthehomologousauto-somepairoft hefemaleisknown:Bothdominantalleles(Aand B)resideononememberofthehomologousautoso mepair,andbothrecessivealleles(aandb) ,a,b,andbonthehomologousautosomepairofth emaleisalsoknown(becausethemaleishomozyg ousforbothtraits) ,(1),1 Meiosesintheheterozygousfemalethatinvolv enocrossoversbetweenthetwolociyieldtwoty pesofeggs:thosepossessingthechromosomewi ththeallelecombina-tionABandthosepossess ingthechromo-somewiththeallelecombinatio nab, }:otherwords,thetwodominantallelesandtth etworecessiveallelesremainlinked.
2 ( ,/--= :J<>+ {some),justastheyareinthe \ ~:---\ >._=.:<..\.\#~.. ; ;2:/==%:>,.,i::,.~;..,f- ;:2?21{ w / l $~ .:i:> G;~{// * 4 /,,T )~~/ *.&y,3-,-- .Aj*. + ,,/ % .///,-.$,\/~. meiosesinthefemalethatinvolveasinglecros soverbetweenthetwoloci(oranyoddnumberofc rossovers) ,asinglecrossoverbetweenthetwolocies-tab lisheslinkagebetweenonedominantandonerec essiveallele,Ontheotherhand,meiosesinthe doublyhomozygousmale,whetherornottheyinv ovecross-oversbetweenthetwoloci, ,eachcorrespondingtooneofthefourpossible phenotypes:AB/abfemalexab/abmale >AB/ab+ab/ab+Ab/ab+ (AB/ah), (ab/ah), (Ab/ah), (aB/ab).}}}
3 Alltheoffspringexhibitingthelasttwopheno -types(thecombinationsofonerecessivetrai tvariantandonedominanttraitvariant) ,107=0,053+ ,Thatvaluefortheso-calledrecombinationfr actioncorrespondstoageneticdistanceofabo ut12centimorgans.(Therelationshipbetween recombinaticmfractionandgeneticdistancei spresentedin ClassicalLinkageMapping in fMappirlgtheGenome, )Theparticipantsintheotherbreedingthatpr ovidesunambiguousrecombination-frac-tion dataare,liketheparticipantsinbreed-ing1, ,thesecondfemaleisknowntobeaproduct01the breedingAb/AbxaB/aB(ratherthanthebreedin gAB/ABxab/ab).Thereforethedistributionof allelesonherhomologousautosomepairisAb/a B(ratherthanAB/a~5).
4 (Thedifferenceinalleledistri-butionsofth etwodoublyheterozygousfemalesisoftenrefe rredtoasadifferenceinlinkagephase.)These condbreedingisthussymbolizedbyAb/aBfemal exab/abmale.(2)Breeding2yieldsoffspringt hatexhibitthesamegenotypesandphenotypesa sbreed-ing1:Ab/aE?femalexab/abmaleAb/ b+aB/ab+AB/ab+ (Ab/ah), (aE1/ah), (AB/ah), (ah/ah),Agaitl, ,whichcorrespondstoageneticdistanceofabo ut15centimorgans, , (thatis,abreedingbetweenadoublyheterozyg ousmaleandadoublyhomozygous-recessivefem ale).Then,thecrossoversdetectedarethoset hatoccurduringmeiosesinthe,----maleparen tratherthaninthe\ , ,andgeneticdistancesforotherspeciescanbe determinedbycarryingouteitherbreeding1,s ay, ,considerthefruit-flybreedingAB/abfemale xAB/abmale.
5 (3) :redeyesandnormalwings(Af3/Af3andA/3/ah) andpurpleeyesandvestigialwings(ab/ab).No wassumethatcrossingoverdoesoccurduringme iosesinthefemaleparent,Thenamongtheoffsp ringofbreeding3aresomethatexhibitthetwoo therpossiblepheno-types:redeyesandvestig ialwings(Ab/ab)andpurpleeyesandnormalwin gs(aB/ab).Alloffspringthatexhibitthosetw opheno-typesresultonlyfromcrossingover,H ow-ever,crossingoveralsoleadstooffspring thatexhibitoneofthephenotypesproducedint heabsenceofcrossingover,namely,redeyesan dnormalwings(Ab\ABandaB/Af3).Inotherword s, ,inaddition, ,sincethebreedingofhumanscannotbemanipul ated,thegeno-typesandalleledistributions ofhumanpar-entsarenotalwaysknown, 1>>+.
6 < ,typeintotwocategories-thosethat }.,.<$1<-,..:aretheresultofcrossoversandthose!~,:Yj,-. thatarenot theoffspringresultingfrom ~breeding3cannotbesosortedbecausemeiosesthatdoanddonotinvolvecross-oversresultinthedoublydominantpheno-type,35 UnderstandingInheritancecelldisplaysacharacteristicpatternofdarkandlightbandswhenstainedwithanappropriatedye(see Chromosomes:TheSitesofHereditaryInformation ).BecaLlsethebandingpatterncharacteristicofapairofhomologousmetaphasechromosomesvariesalongthelengthofthechromosomes, (Theincidenceofaberrantchromosomes,liketheincidenceofgenemutations,canbeincreasedbyexposuretoxraysorothermutagenicagents.)
7 Severaltypesofchromosomeaberrations,orre arrangements,werenoted,includingtransloc ations(theexchangeofchromosomeregionsbet weennonhomologouschromosomes)andinversio ns(thereversaloftheorientationofachromos omeregion).Obviouslyachromosomerearrange mentcanleadtochangesinthecomplement, (or-genes)affectedbyachromosomerearrange ment(asdeterminedfromgeneticdata) , anchor agenetic-linkagemapincludingthatgenetoth echromosome,(Recallthatalinkageanalysisp rovidesonlydistancesbetweengenesonachrom osome;additionalinformationisrequiredtol ocatethegenesrelativetothechromosomeitse lf.)Chromosomerearrangementsandgenemut:~ tionsarebuttwoexamplesofnaturallyrarephe nomenathat,oncenoted, (andotherinsectsoftheorderDiptera).
8 (1889 [969)andindependentlytwoGermangeneticist sdiscoveredthatthechromosomesinthosecell sweremicroscopicallyvis-ibleduringinterp hase.(Interphasechromosomesareusuallynot microscopicallyvisiblebecausetheyhavenot yetcondensedinpreparationformitosis.)For someunknownreasonthesalivarycellsofDwsop hi[aundergonotasingleroundbutmanysuccess iveroundsofchromosomeduplicationduringth eSphaseofinterphase(see TheEukaryoticCellCycle ),Thenumerous(ontheorderofathousand)copi esofeachchromosomeremaincloselyassociate dalongtheirlengths, polytene chromos-omesarenotcondensed, , , ,whentheFrenchgeneticistLucienClaudeCu&m t(1866 1951) (1857 1936)establishedthatthehumandiseasealkap tonuriawasinheritedasarecessivetraitvari antandproposedthattheunmistakablesymptom ofthedisease(urinethatblackensafterbeing excreted)]]
9 Wasduetoaccumulationintheurineofametabol icproductthatnormallyisdegradedwiththehe lpofacertainenzyme.(Anenzymeisaproteinth atcatalyzesabiochemicalreaction.)ButCu6n ot sandGarrod ,in1941,theAmericangeneticistGeorgeWells Beadle(1903 1989)andtheAmericanbiochemistEdwardLawri eTatum(1909 1975)clearlydemonstratedtheconnectionbet weenthegenesanorganismpossessesandthebio chemica] , (onecontainingonlysucrose,inorganicsalts ,andthevitaminbiotin), ,BeadleandTatumproducedaveryfewmutantspo resthatcouldnotbeculturedonaminimalgrowt hmediumbutcouldbeculturedonagrowthmedium containingasingleadditionalnutrient(vita minB6,forexample).
10 Theyconcludedthatthe~ ,andin1948theAmericangeneticistandbioche mistNormanHaroldHorowitz(1915 )propoundedthefamousonegene+ shypothesishassincebeenmodifiedtostateth atonegenedirectsthesynthesisofoneprotein ,or,moreprecisely,onepolypeptidechain, ,atenantofthevertebrategut, ~oisJacob([920-),JoshuaLederberg(1925-), JacquesLucienMonod(1910-1976),andElieLeo Wollman(1917 ), ,includingtheirregulation, ,thesimplestofallorganisms,andinparticul aronthevirusesthatinfectbacteria,knownas bacteriophagesorsimplyphages.( ,however,reproduce byusurpingthebiosyntheticmachineryofthec ellstheyinfect andpasstheircharacteristicsfromgeneratio ntogenerationthroughthemediumofgenesjust ascellularorganismsdo.)]
