Chapter14

MendelandtheGeneIdea
LectureOutline
Overview
Everydayweobserveheritablevariations(suchasbrown,green,orblueeyes)among
individualsinapopulation.

Thesetraitsaretransmittedfromparentstooffspring.

Onepossibleexplanationforheredityisablendinghypothesis.
Thishypothesisproposesthatgeneticmaterialcontributedbyeachparentmixesina
manneranalogoustothewayblueandyellowpaintsblendtomakegreen.
Withblendinginheritance,afreelymatingpopulationwilleventuallygiverisetoa
uniformpopulationofindividuals.
Everydayobservationsandtheresultsofbreedingexperimentstellusthatheritabletraits
donotblendtobecomeuniform.

Analternativemodel,particulateinheritance,proposesthatparentspassondiscrete
heritableunits,genes,thatretaintheirseparateidentitiesinoffspring.
Genescanbesortedandpassedon,generationaftergeneration,inundilutedform.
Moderngeneticsbeganinanabbeygarden,whereamonknamedGregorMendel
documentedaparticulatemechanismofinheritance.
A.GregorMendelsDiscoveries
1.Mendelbroughtanexperimentalandquantitativeapproachtogenetics.
Mendeldiscoveredthebasicprinciplesofhereditybybreedinggardenpeasincarefully
plannedexperiments.

MendelgrewuponasmallfarminwhatistodaytheCzechRepublic.

In1843,MendelenteredanAugustinianmonastery.

HestudiedattheUniversityofViennafrom1851to1853,wherehewasinfluencedbya
physicistwhoencouragedexperimentationandtheapplicationofmathematicstoscienceand
byabotanistwhostimulatedMendelsinterestinthecausesofvariationinplants.

TheseinfluencescametogetherinMendelsexperiments.

Afteruniversity,MendeltaughtattheBrunnModernSchoolandlivedinthelocal
monastery.
Themonksatthismonasteryhadalongtraditionofinterestinthebreedingofplants,
includingpeas.

Around1857,Mendelbeganbreedinggardenpeastostudyinheritance.

Peaplantshaveseveraladvantagesforgeneticstudy.
IG Lecture Outline 14-1

Peaplantsareavailableinmanyvarietieswithdistinctheritablefeatures,orcharacters,
withdifferentvarianttraits.
Mendelcouldstrictlycontrolwhichplantsmatedwithwhich.
Eachpeaplanthasmale(stamens)andfemale(carpal)sexualorgans.
Innature,peaplantstypicallyselffertilize,fertilizingovawiththespermnucleifrom
theirownpollen.
However,Mendelcouldalsousepollenfromanotherplantforcrosspollination.

Mendeltrackedonlythosecharactersthatvariedinaneitherormanner,ratherthana
moreorlessmanner.
Forexample,heworkedwithflowersthatwereeitherpurpleorwhite.
Heavoidedtraits,suchasseedweight,thatvariedonacontinuum.

Mendelstartedhisexperimentswithvarietiesthatweretruebreeding.
Whentruebreedingplantsselfpollinate,alltheiroffspringhavethesametraits.

Inatypicalbreedingexperiment,Mendelwouldcrosspollinate(hybridize)two
contrasting,truebreedingpeavarieties.
ThetruebreedingparentsarethePgeneration,andtheirhybridoffspringaretheF1
generation.

MendelwouldthenallowtheF1hybridstoselfpollinatetoproduceanF2generation.

ItwasmainlyMendelsquantitativeanalysisofF 2plantsthatrevealedtwofundamental
principlesofheredity:thelawofsegregationandthelawofindependentassortment.
2.Bythelawofsegregation,thetwoallelesforacharacterareseparatedduringtheformation
ofgametes.
Iftheblendingmodelwascorrect,theF1hybridsfromacrossbetweenpurpleflowered
andwhitefloweredpeaplantswouldhavepalepurpleflowers.
Instead,F1hybridsallhavepurpleflowers,justaspurpleastheirpurpleflowered
parents.
WhenMendelallowedtheF1plantstoselffertilize,theF2generationincludedboth
purplefloweredandwhitefloweredplants.
Thewhitetrait,absentintheF1,reappearedintheF2.

Mendelusedverylargesamplesizesandkeptaccuraterecordsofhisresults.
Mendelrecorded705purplefloweredF2plantsand224whitefloweredF2plants.
ThiscrossproducedatraitsratioofthreepurpletoonewhiteintheF 2offspring.

MendelreasonedthattheheritablefactorforwhiteflowerswaspresentintheF 1plants,
butdidnotaffectflowercolor.
Purpleflowercolorisadominanttrait,andwhiteflowercolorisarecessivetrait.
ThereappearanceofwhitefloweredplantsintheF2generationindicatedthatthe
heritablefactorforthewhitetraitwasnotdilutedorblendedbycoexistingwiththepurple
flowerfactorinF1hybrids.
Mendelfoundsimilar3to1ratiosoftwotraitsamongF 2offspringwhenheconducted
crossesforsixothercharacters,eachrepresentedbytwodifferenttraits.
Forexample,whenMendelcrossedtwotruebreedingvarieties,oneproducinground
seedsandtheotherproducingwrinkledseeds,alltheF1offspringhadroundseeds.
IntheF2plants,75%oftheseedswereroundand25%werewrinkled.
IG Lecture Outline 14-2

 Mendeldevelopedahypothesistoexplaintheseresultsthatconsistedoffourrelated
ideas.Wewillexplaineachideawiththemodernunderstandingofgenesandchromosomes.
1.
Alternativeversionsofgenesaccountforvariationsininheritedcharacters.
Thegeneforflowercolorinpeaplantsexistsintwoversions,oneforpurpleflowersand
oneforwhiteflowers.
Thesealternateversionsarecalledalleles.
Eachgeneresidesataspecificlocusonaspecificchromosome.
TheDNAatthatlocuscanvaryinitssequenceofnucleotides.
ThepurpleflowerandwhiteflowerallelesaretwoDNAvariationsattheflowercolor
locus.
2.
Foreachcharacter,anorganisminheritstwoalleles,onefromeachparent.
Adiploidorganisminheritsonesetofchromosomesfromeachparent.
Eachdiploidorganismhasapairofhomologouschromosomesand,therefore,two
copiesofeachgene.
Thesehomologouslocimaybeidentical,asinthetruebreedingplantsoftheP
generation.
Alternatively,thetwoallelesmaydiffer.
3.
Ifthetwoallelesatalocusdiffer,thenone,thedominantallele,determinesthe
organismsappearance.Theother,therecessiveallele,hasnonoticeableeffectonthe
organismsappearance.
Intheflowercolorexample,theF 1plantsinheritedapurpleflowerallelefromoneparent
andawhiteflowerallelefromtheother.
Theyhadpurpleflowersbecausethealleleforthattraitisdominant.
4.
4.Mendelslawofsegregationstatesthatthetwoallelesforaheritable
characterseparateandsegregateduringgameteproductionandendupindifferent
gametes.
Thissegregationofallelescorrespondstothedistributionofhomologouschromosomes
todifferentgametesinmeiosis.
Ifanorganismhastwoidenticalallelesforaparticularcharacter,thenthatalleleis
presentasasinglecopyinallgametes.
Ifdifferentallelesarepresent,then50%ofthegameteswillreceiveonealleleand50%
willreceivetheother.
Mendelslawofsegregationaccountsforthe3:1ratiothatheobservedintheF 2
generation.
TheF1hybridsproducetwoclassesofgametes,halfwiththepurplefloweralleleandhalf
withthewhiteflowerallele.

Duringselfpollination,thegametesofthesetwoclassesuniterandomly.

Thisproducesfourequallylikelycombinationsofspermandovum.

APunnettsquarepredictstheresultsofageneticcrossbetweenindividualsofknown
genotype.

LetusdescribeaPunnettsquareanalysisoftheflowercolorexample.

Wewilluseacapitallettertosymbolizethedominantalleleandalowercaseletterto
symbolizetherecessiveallele.
Pisthepurpleflowerallele,andpisthewhiteflowerallele.

WhatwillbethephysicalappearanceoftheF2offspring?
IG Lecture Outline 14-3

OneinfourF2offspringwillinherittwowhiteflowerallelesandproducewhiteflowers.
HalfoftheF2offspringwillinheritonewhitefloweralleleandonepurpleflowerallele
andproducepurpleflowers.
OneinfourF2offspringwillinherittwopurpleflowerallelesandproducepurple
flowers.

Mendelsmodelaccountsforthe3:1ratiointheF2generation.

Anorganismwithtwoidenticalallelesforacharacterishomozygousforthatcharacter.

Organismswithtwodifferentallelesforacharacterisheterozygousforthatcharacter.

Anorganismstraitsarecalleditsphenotype.

Itsgeneticmakeupiscalleditsgenotype.
Twoorganismscanhavethesamephenotypebuthavedifferentgenotypesifoneis
homozygousdominantandtheotherisheterozygous.

Forflowercolorinpeas,theonlyindividualswithwhiteflowersarethosethatare
homozygousrecessive(pp)fortheflowercolorgene.
However,PPandPpplantshavethesamephenotype(purpleflowers)butdifferent
genotypes(homozygousdominantandheterozygous).

Howcanwetellthegenotypeofanindividualwiththedominantphenotype?
Theorganismmusthaveonedominantallele,butcouldbehomozygousdominantor
heterozygous.

Theansweristocarryoutatestcross.
Themysteryindividualisbredwithahomozygousrecessiveindividual.
Ifanyoftheoffspringdisplaytherecessivephenotype,themysteryparentmustbe
heterozygous.

3.Bythelawofindependentassortment,eachpairofallelessegregatesindependentlyinto
gametes.

Mendelsfirstexperimentsfollowedonlyasinglecharacter,suchasflowercolor.
AllF1progenyproducedinthesecrossesweremonohybrids,heterozygousforone
character.
Acrossbetweentwoheterozygotesisamonohybridcross.

Mendelidentifiedthesecondlawofinheritancebyfollowingtwocharactersatthesame
time.

Inonesuchdihybridcross,Mendelstudiedtheinheritanceofseedcolorandseedshape.
Thealleleforyellowseeds(Y)isdominanttothealleleforgreenseeds(y).
Thealleleforroundseeds(R)isdominanttothealleleforwrinkledseeds(r).

Mendelcrossedtruebreedingplantsthathadyellow,roundseeds(YYRR)withtrue
breedingplantsthathasgreen,wrinkledseeds(yyrr).
Onepossibilityisthatthetwocharactersaretransmittedfromparentstooffspringasa
package.
TheYandRallelesandyandrallelesstaytogether.

Ifthiswerethecase,theF1offspringwouldproduceyellow,roundseeds.

TheF2offspringwouldproducetwophenotypes(yellow+round;green+wrinkled)ina
3:1ratio,justlikeamonohybridcross.
IG Lecture Outline 14-4

ThiswasnotconsistentwithMendelsresults.

Analternativehypothesisisthatthetwopairsofallelessegregateindependentlyofeach
other.
Thepresenceofaspecificalleleforonetraitinagametehasnoimpactonthepresence
ofaspecificalleleforthesecondtrait.

Inourexample,theF1offspringwouldstillproduceyellow,roundseeds.

However,whentheF1sproducedgametes,geneswouldbepackagedintogameteswith
allpossiblealleliccombinations.
Fourclassesofgametes(YR,Yr,yR,andyr)wouldbeproducedinequalamounts.
Whenspermwithfourclassesofallelesandovawithfourclassesofallelescombined,
therewouldbe16equallyprobablewaysinwhichtheallelescancombineintheF 2
generation.

Thesecombinationsproducefourdistinctphenotypesina9:3:3:1ratio.

ThiswasconsistentwithMendelsresults.

Mendelrepeatedthedihybridcrossexperimentforotherpairsofcharactersandalways
observeda9:3:3:1phenotypicratiointheF2generation.

Eachcharacterappearedtobeinheritedindependently.

Ifyoufollowjustonecharacterinthesecrosses,youwillobservea3:1F 2ratio,justasif
thiswereamonohybridcross.
Theindependentassortmentofeachpairofallelesduringgameteformationisnowcalled
Mendelslawofindependentassortment.
Mendelslawofindependentassortmentstatesthateachpairofallelessegregates
independentlyduringgameteformation.
Strictlyspeaking,thislawappliesonlytogeneslocatedondifferent,nonhomologous
chromosomes.
Geneslocatedneareachotheronthesamechromosometendtobeinheritedtogetherand
havemorecomplexinheritancepatternsthanthosepredictedforthelawofindependent
assortment.
4.ThelawsofprobabilitygovernMendelianinheritance.
Mendelslawsofsegregationandindependentassortmentreflectthesamelawsof
probabilitythatapplytotossingcoinsorrollingdice.
Theprobabilityscalerangesfrom0(aneventwithnochanceofoccurring)to1(anevent
thatiscertaintooccur).
Theprobabilityoftossingheadswithanormalcoinis1/2.
Theprobabilityofrollinga3withasixsideddieis1/6,andtheprobabilityofrollingany
othernumberis11/6=5/6.
Whentossingacoin,theoutcomeofonetosshasnoimpactontheoutcomeofthenext
toss.

Eachtossisanindependentevent,justlikethedistributionofallelesintogametes.
Likeacointoss,eachovumfromaheterozygousparenthasa1/2chanceofcarryingthe
dominantalleleanda1/2chanceofcarryingtherecessiveallele.
Thesameoddsapplytothesperm.
IG Lecture Outline 14-5

 Wecanusethemultiplicationruletodeterminethechancethattwoormoreindependent
eventswilloccurtogetherinsomespecificcombination.
Computetheprobabilityofeachindependentevent.
Multiplytheindividualprobabilitiestoobtaintheoverallprobabilityoftheseevents
occurringtogether.
Theprobabilitythattwocoinstossedatthesametimewilllandheadsupis1/21/2=
1/4.
Similarly,theprobabilitythataheterozygouspeaplant(Pp)willselffertilizetoproduce
awhitefloweredoffspring(pp)isthechancethataspermwithawhiteallelewillfertilize
anovumwithawhiteallele.
Thisprobabilityis1/21/2=1/4.

Theruleofmultiplicationalsoappliestodihybridcrosses.
Foraheterozygousparent(YyRr)theprobabilityofproducingaYRgameteis1/21/2=
1/4.
WecanusethistopredicttheprobabilityofaparticularF 2genotypewithoutconstructing
a16partPunnettsquare.
TheprobabilitythatanF2plantfromheterozygousparentswillhaveaYYRRgenotypeis
1/16(1/4chanceforaYRovumand1/4chanceforaYRsperm).
Theruleofadditionalsoappliestogeneticproblems.

Undertheruleofaddition,theprobabilityofaneventthatcanoccurtwoormore
differentwaysisthesumoftheseparateprobabilitiesofthoseways.
Forexample,therearetwowaysthatF1gametescancombinetoformaheterozygote.
Thedominantallelecouldcomefromthespermandtherecessivefromtheovum
(probability=1/4).
Orthedominantallelecouldcomefromtheovumandtherecessivefromthesperm
(probability=1/4).
Theprobabilityofobtainingaheterozygoteis1/4+1/4=1/2.
Wecancombinetherulesofmultiplicationandadditiontosolvecomplexproblemsin
Mendeliangenetics.
Letsdeterminetheprobabilityofanoffspringhavingtworecessivephenotypesforat
leasttwoofthreetraitsresultingfromatrihybridcrossbetweenpeaplantsthatarePpYyRr
andPpyyrr.
Therearefivepossiblegenotypesthatfulfillthiscondition:ppyyRr,ppYyrr,Ppyyrr,
PPyyrr,andppyyrr.
Wecanusetheruleofmultiplicationtocalculatetheprobabilityforeachofthese
genotypesandthenusetheruleofadditiontopooltheprobabilitiesforfulfillingthe
conditionofatleasttworecessivetraits.

TheprobabilityofproducingappyyRroffspring:
Theprobabilityofproducingpp=1/21/2=1/4.
Theprobabilityofproducingyy=1/21=1/2.
TheprobabilityofproducingRr=1/21=1/2.
Therefore,theprobabilityofallthreebeingpresent(ppyyRr)inoneoffspringis1/41/2
1/2=1/16.

ForppYyrr:1/41/21/2=1/16.

ForPpyyrr:1/21/21/2=1/8or2/16.
IG Lecture Outline 14-6

ForPPyyrr:1/41/21/2=1/16.

Forppyyrr:1/41/21/2=1/16.

Therefore,thechancethatagivenoffspringwillhaveatleasttworecessivetraitsis1/16
+2/16+1/16+1/16=6/16.
5.Mendeldiscoveredtheparticulatebehaviorofgenes:areview.
Whilewecannotpredictwithcertaintythegenotypeorphenotypeofanyparticularseed
fromtheF2generationofadihybridcross,wecanpredicttheprobabilitythatitwillhavea
specificgenotypeorphenotype.
Mendelsexperimentssucceededbecausehecountedsomanyoffspring,wasableto
discernthestatisticalnatureofinheritance,andhadakeensenseoftherulesofchance.
Mendelslawsofindependentassortmentandsegregationexplainheritablevariationin
termsofalternativeformsofgenesthatarepassedalongaccordingtosimplerulesof
probability.
Theselawsapplynotjusttogardenpeas,buttoalldiploidorganismsthatreproduceby
sexualreproduction.
Mendelsstudiesofpeainheritanceendurenotonlyingenetics,butasacasestudyofthe
powerofscientificreasoningusingthehypotheticodeductiveapproach.
B.ExtendingMendelianGenetics
1.Therelationshipbetweengenotypeandphenotypeisrarelysimple.
Inthe20thcentury,geneticistshaveextendedMendelianprinciplesnotonlytodiverse
organisms,butalsotopatternsofinheritancemorecomplexthanMendeldescribed.
Infact,Mendelhadthegoodfortunetochooseasystemthatwasrelativelysimple
genetically.
EachcharacterthatMendelstudiediscontrolledbyasinglegene.
Eachgenehasonlytwoalleles,oneofwhichiscompletelydominanttotheother.
TheheterozygousF1offspringofMendelscrossesalwayslookedlikeoneoftheparental
varietiesbecauseoneallelewasdominanttotheother.

Therelationshipbetweengenotypeandphenotypeisrarelysosimple.

Theinheritanceofcharactersdeterminedbyasinglegenedeviatesfromsimple
Mendelianpatternswhenallelesarenotcompletelydominantorrecessive,whenagenehas
morethantwoalleles,orwhenageneproducesmultiplephenotypes.

Wewillconsiderexamplesofeachofthesesituations.

Allelesshowdifferentdegreesofdominanceandrecessivenessinrelationtoeachother.

OneextremeisthecompletedominancecharacteristicofMendelscrosses.

Attheotherextremefromcompletedominanceiscodominance,inwhichtwoalleles
affectthephenotypeinseparate,distinguishableways.
Forexample,theM,N,andMNbloodgroupsofhumansareduetothepresenceoftwo
specificmoleculesonthesurfaceofredbloodcells.
PeopleofgroupM(genotypeMM)haveonetypeofmoleculeontheirredbloodcells,
peopleofgroupN(genotypeNN)havetheothertype,andpeopleofgroupMN
(genotypeMN)havebothmoleculespresent.
IG Lecture Outline 14-7

TheMNphenotypeisnotintermediatebetweenMandNphenotypesbutratherexhibits
boththeMandtheNphenotype.

Someallelesshowincompletedominance,inwhichheterozygotesshowadistinct
intermediatephenotypenotseeninhomozygotes.
Thisisnotblendinginheritancebecausethetraitsareseparable(particulate),asshownin
furthercrosses.
Offspringofacrossbetweenheterozygotesshowthreephenotypes:eachparentalandthe
heterozygote.
Thephenotypicandgenotypicratiosareidentical:1:2:1.

Aclearexampleofincompletedominanceisseeninflowercolorofsnapdragons.
AcrossbetweenawhitefloweredplantandaredfloweredplantwillproduceallpinkF 1
offspring.
SelfpollinationoftheF1offspringproduces25%white,25%red,and50%pinkF2
offspring.

Therelativeeffectsoftwoallelesrangefromcompletedominanceofoneallele,through
incompletedominanceofeitherallele,tocodominanceofbothalleles.
Itisimportanttorecognizethatadominantalleledoesnotsomehowsubduearecessive
allele.

Allelesaresimplyvariationsinagenesnucleotidesequence.
Whenadominantallelecoexistswitharecessivealleleinaheterozygote,theydonot
interactatall.

Toillustratetherelationshipbetweendominanceandphenotype,letusconsiderMendels
characterofroundversuswrinkledpeaseedshape.
Peaplantswithwrinkledseedshavetwocopiesoftherecessiveallele.
Theseedsarewrinkledduetotheaccumulationofmonosaccharidesbecauseofthelack
ofakeyenzymethatconvertsthemtostarch.
Excesswaterenterstheseedduetotheaccumulationofmonosaccharides.
Theseedswrinklewhentheexcesswaterdries.
Bothhomozygousdominantsandheterozygotesproduceenoughenzymestoconvertall
themonosaccharidesintostarch.
Asaresult,theydonotfillwithexcesswaterandformsmoothseedsastheydry.
Foranycharacter,dominance/recessivenessrelationshipsdependonthelevelatwhich
weexaminethephenotype.
Forexample,humanswithTaySachsdiseaselackafunctioningenzymetometabolize
certainlipids.Theselipidsaccumulateinthebrain,harmingbraincells,andultimately
leadingtodeath.
ChildrenwithtwoTaySachsalleles(homozygotes)havethedisease.
Bothheterozygoteswithoneworkingalleleandhomozygoteswithtwoworkingalleles
arehealthyandnormalattheorganismallevel.
Theactivitylevelofthelipidmetabolizingenzymeisreducedinheterozygotes.Atthe
biochemicallevel,theallelesshowincompletedominance.
Heterozygousindividualsproduceequalnumbersofnormalanddysfunctionalenzyme
molecules.Atthemolecularlevel,theTaySachsandfunctionalallelesarecodominant.
Adominantalleleisnotnecessarilymorecommoninapopulationthantherecessive
allele.
IG Lecture Outline 14-8

Forexample,onebabyin400isbornwithpolydactyly,aconditioninwhichindividuals
arebornwithextrafingersortoes.
Polydactylyisduetoadominantallele.
However,therecessivealleleisfarmoreprevalentthanthedominantallele.
399individualsoutof400havefivedigitsperappendage.

Manygenesexistinpopulationsinmorethantwoallelicforms.

TheABObloodgroupsinhumansaredeterminedbythreealleles,IA,IB,andi.
BoththeIAandIBallelesaredominanttotheiallele.
TheIAandIBallelesarecodominanttoeachother.

Becauseeachindividualcarriestwoalleles,therearesixpossiblegenotypesandfour
possiblebloodtypes.
IndividualsthatareIAIAorIAiaretypeAandhavetypeAcarbohydratesonthesurfaceof
theirredbloodcells.
IndividualsthatareIBIBorIBiaretypeBandhavetypeBcarbohydratesonthesurfaceof
theirredbloodcells.
IndividualsthatareIAIBaretypeABandhavebothtypeAandtypeBcarbohydrateson
thesurfaceoftheirredbloodcells.
IndividualsthatareiiaretypeOandhaveneithercarbohydrateonthesurfaceoftheirred
bloodcells.
Matchingcompatiblebloodgroupsiscriticalforbloodtransfusionsbecauseaperson
producesantibodiesagainstforeignbloodfactors.
IfthedonorsbloodhasanAorBcarbohydratethatisforeigntotherecipient,antibodies
intherecipientsbloodwillbindtotheforeignmolecules,causethedonatedbloodcells
toclumptogether,andcankilltherecipient.

Thegenesthatwehavecoveredsofaraffectonlyonephenotypiccharacter.

However,mostgenesarepleiotropic,affectingmorethanonephenotypiccharacter.
Forexample,thewiderangingsymptomsofsicklecelldiseaseareduetoasinglegene.

Consideringtheintricatemolecularandcellularinteractionsresponsibleforan
organismsdevelopment,itisnotsurprisingthatagenecanaffectanumberof
characteristics.
Inepistasis,ageneatonelocusaltersthephenotypicexpressionofageneatasecond
locus.
Forexample,inmiceandmanyothermammals,coatcolordependsontwogenes.
One,theepistaticgene,determineswhetherpigmentwillbedepositedinhairornot.
Presence(C)isdominanttoabsence(c)ofpigment.
Thesecondgenedetermineswhetherthepigmenttobedepositedisblack(B)orbrown
(b).
Theblackalleleisdominanttothebrownallele.
Anindividualthatiscchasawhite(albino)coatregardlessofthegenotypeofthesecond
gene.
Acrossbetweentwoblackmicethatareheterozygous(BbCc)willfollowthelawof
independentassortment.
However,unlikethe9:3:3:1offspringratioofanormalMendelianexperiment,the
offspringratioisnineblack,threebrown,andfourwhite.
IG Lecture Outline 14-9

Allccmicewillbealbino,regardlessoftheallelestheyinheritattheBgene.

Somecharacterscannotbeclassifiedaseitheror,asMendelsgeneswere.

Quantitativecharactersvaryinapopulationalongacontinuum.

Theseareusuallyduetopolygenicinheritance,theadditiveeffectsoftwoormoregenes
onasinglephenotypiccharacter.
Forexample,skincolorinhumansiscontrolledbyatleastthreeindependentgenes.
Imaginethateachgenehastwoalleles,onelightandonedark,whichdemonstrate
incompletedominance.
AnAABBCCindividualisverydark;anaabbccindividualisverylight.
AcrossbetweentwoAaBbCcindividuals(withintermediateskinshade)willproduce
offspringcoveringawiderangeofshades.
Individualswithintermediateskinshadeswillbemostcommon,butsomeverylightand
verydarkindividualscouldbeproducedaswell.
Therangeofphenotypeswillformanormaldistribution,ifthenumberofoffspringis
greatenough.

Phenotypedependsonenvironmentandgenes.
Apersonbecomesdarkeriftheytan,despitetheirinheritedskincolor.
Asingletreemayhaveleavesthatvaryinsize,shape,andgreenness,dependingon
exposuretowindandsun.
Forhumans,nutritioninfluencesheight,exercisealtersbuild,suntanningdarkensskin,
andexperienceimprovesperformanceonintelligencetests.
Evenidenticaltwins,whoaregeneticallyidentical,accumulatephenotypicdifferencesas
aresultoftheiruniqueexperiences.

Therelativeimportanceofgenesandtheenvironmentininfluencinghuman
characteristicsisaveryoldandhotlycontesteddebate.
Theproductofagenotypeisgenerallynotarigidlydefinedphenotype,butarangeof
phenotypicpossibilities,thenormofreaction,thataredeterminedbytheenvironment.
Insomecases,thenormofreactionhasnobreadth,andagivengenotypespecifiesa
particularphenotype(forexample,bloodtype).
Incontrast,apersonsredandwhitebloodcellcountvarieswithfactorssuchasaltitude,
customaryexerciselevel,andpresenceofinfection.

Normsofreactionarebroadestforpolygeniccharacters.
Forthesemultifactorialcharacters,environmentcontributestotheirquantitativenature.

Areductionistemphasisonsinglegenesandsinglephenotypiccharacterspresentsan
inadequateperspectiveonheredityandvariation.

AmorecomprehensivetheoryofMendeliangeneticsmustvieworganismsasawhole.

Thetermphenotypecanrefernotonlytospecificcharacterssuchasflowercolororblood
group,butalsotoanorganisminitsentirety,includingallaspectsofitsphysicalappearance.
Genotypecanrefernotjusttoasinglegeneticlocus,butalsotoanorganismsentire
geneticmakeup.
Anorganismsphenotypereflectsitsoverallgenotypeanditsuniqueenvironmental
history.
C.MendelianInheritanceinHumans
IG Lecture Outline 14-10

Whilepeasareconvenientsubjectsforgeneticresearch,humansarenot.
Thegenerationtimeistoolong,fecundityistoolow,andbreedingexperimentsare
unacceptable.

Yethumansaresubjecttothesamerulesgoverninginheritanceasotherorganisms.

Newtechniquesinmolecularbiologyhaveledtomanybreakthroughdiscoveriesinthe
studyofhumangenetics.
1.PedigreeanalysisrevealsMendelianpatternsinhumaninheritance.
Ratherthanmanipulatematingpatternsofpeople,geneticistsanalyzetheresultsof
matingsthathavealreadyoccurred.
Inapedigreeanalysis,informationaboutthepresenceorabsenceofaparticular
phenotypictraitiscollectedfromasmanyindividualsinafamilyaspossible,across
generations.

Thedistributionofthesecharactersisthenmappedonthefamilytree.
Forexample,theoccurrenceofwidowspeak(W)isdominanttoastraighthairline(w).
Phenotypesoffamilymembersandknowledgeofdominant/recessiverelationsbetween
allelesallowresearcherstopredictthegenotypesofmembersofthisfamily.
Forexample,ifanindividualinthethirdgenerationlacksawidowspeak,butbothher
parentshavewidowspeaks,thenherparentsmustbeheterozygousforthatgene.
Ifsomesiblingsinthesecondgenerationlackawidowspeakandoneofthe
grandparents(firstgeneration)alsolacksone,thenweknowtheothergrandparentmust
beheterozygous,andwecandeterminethegenotypeofmanyotherindividuals.

Wecanusethesamefamilytreetotracethedistributionofattachedearlobes(f),a
recessivecharacteristic.

Individualswithadominantallele(F)havefreeearlobes.

Someindividualsmaybeambiguous,especiallyiftheyhavethedominantphenotypeand
couldbeheterozygousorhomozygousdominant.

Apedigreecanhelpusunderstandthepastandpredictthefuture.

WecanusenormalMendelianrules,includingmultiplicationandaddition,topredictthe
probabilityofspecificphenotypes.
Forexample,theserulescouldbeusedtopredicttheprobabilitythatachildwithWwFf
parentswillhaveawidowspeakandattachedearlobes.
Thechanceofhavingawidowspeakis3/4(1/2[WW]+1/4[Ww]).
Thechanceofhavingattachedearlobesis1/4[ff].
Thiscombinationhasaprobabilityof3/41/4=3/16.
2.ManyhumandisordersfollowMendelianpatternsofinheritance.
Thousandsofgeneticdisorders,includingdisablingordeadlyhereditarydiseases,are
inheritedassimplerecessivetraits.
Theseconditionsrangefromrelativelymild(albinism)tolifethreatening(cystic
fibrosis).
Therecessivebehavioroftheallelescausingtheseconditionsoccursbecausetheallele
codesforamalfunctioningproteinorfornoproteinatall.
Heterozygoteshaveanormalphenotypebecauseonenormalalleleproducesenoughof
therequiredprotein.
IG Lecture Outline 14-11

 Arecessivelyinheriteddisordershowsuponlyinhomozygousindividualswhoinherita
recessiveallelefromeachparent.

Individualswholackthedisorderareeitherhomozygousdominantorheterozygotes.

Whileheterozygotesmaylackobviousphenotypiceffects,theyarecarrierswhomay
transmitarecessivealleletotheiroffspring.

Mostpeoplewithrecessivedisordersareborntocarrierswithnormalphenotypes.
Twocarriershavea1/4chanceofhavingachildwiththedisorder,1/2chanceofhaving
achildwhoisacarrier,and1/4chanceofhavingachildwithoutadefectiveallele.

Geneticdisordersarenotevenlydistributedamongallgroupsofhumans.

Thisresultsfromthedifferentgenetichistoriesoftheworldspeopleduringtimeswhen
populationsweremoregeographicallyandgeneticallyisolated.

Cysticfibrosisstrikesoneofevery2,500whitesofEuropeandescent.
Onein25peopleofEuropeandescentisacarrierforthiscondition.
ThenormalalleleforthisgenecodesforamembraneproteinthattransportsCl between
cellsandextracellularfluid.
Ifthesechannelsaredefectiveorabsent,thereareabnormallyhighextracellularlevelsof
chloride.
Thiscausesthemucuscoatsofcertaincellstobecomethickerandstickierthannormal.
Thismucusbuildupinthepancreas,lungs,digestivetract,andelsewherecausespoor
absorptionofnutrients,chronicbronchitis,andbacterialinfections.
Withouttreatment,affectedchildrendiebeforefive,butwithtreatment,theycanlivepast
theirlate20soreven30s.
TaySachsdiseaseisanotherlethalrecessivedisorder.
Itiscausedbyadysfunctionalenzymethatfailstobreakdownspecificbrainlipids.
Thesymptomsbeginwithseizures,blindness,anddegenerationofmotorandmental
performanceafewmonthsafterbirth.
Inevitably,thechilddiesafterafewyears.
AmongAshkenazicJews(thosefromcentralEurope),thisdiseaseoccursinoneof3,600
births,about100timesgreaterthantheincidenceamongnonJewsorMediterranean
(Sephardic)Jews.

ThemostcommoninheriteddiseaseamongpeopleofAfricandescentissicklecell
disease,whichaffectsoneof400AfricanAmericans.
Sicklecelldiseaseiscausedbythesubstitutionofasingleaminoacidinhemoglobin.
Whenoxygenlevelsinthebloodofanaffectedindividualarelow,sicklecell
hemoglobinaggregateintolongrodsthatdeformredbloodcellsintoasickleshape.
Thissicklingcreatesacascadeofsymptoms,demonstratingthepleiotropiceffectsofthis
allele,assickledcellsclumpandclogcapillariesthroughoutthebody.
Doctorscanuseregularbloodtransfusionstopreventbraindamageandnewdrugsto
preventortreatotherproblems.
Attheorganismallevel,thenonsicklealleleisincompletelydominanttothesicklecell
allele.
Carriersaresaidtohavesicklecelltrait.
Theseindividualsareusuallyhealthy,althoughsomesuffersomesymptomsofsicklecell
diseaseunderbloodoxygenstress.
IG Lecture Outline 14-12

 Atthemolecularlevel,thetwoallelesarecodominantasbothnormalandabnormal
(sicklecell)hemoglobinsaresynthesized.

AboutoneintenAfricanAmericanshassicklecelltrait.
Thehighfrequencyofheterozygotesisunusualforanallelewithseveredetrimental
effectsinhomozygotes.
Individualswithonesicklecellallelehaveincreasedresistancetomalaria,aparasitethat
spendspartofitslifecycleinredbloodcells.
IntropicalAfrica,wheremalariaiscommon,thesicklecellalleleisbothaboonanda
bane.
Homozygousnormalindividualsdieofmalariaandhomozygousrecessive
individualsdieofsicklecelldisease,whilecarriersarerelativelyfreeofboth.

TherelativelyhighfrequencyofsicklecelltraitinAfricanAmericansisavestigeof
theirAfricanroots.
Normallyitisrelativelyunlikelythattwocarriersofthesamerare,harmfulallelewill
meetandmate.

However,consanguineousmatingsbetweencloserelativesincreasetherisk.
Individualswhosharearecentcommonancestoraremorelikelytocarrythesame
recessivealleles.

Mostsocietiesandcultureshavelawsortaboosforbiddingmarriagesbetweenclose
relatives.
Althoughmostharmfulallelesarerecessive,anumberofhumandisordersaredueto
dominantalleles.
Forexample,achondroplasia,aformofdwarfism,hasanincidenceofonecasein25,000
people.
Heterozygousindividualshavethedwarfphenotype.
Thosewhoarenotachondroplasticdwarfs,99.99%ofthepopulation,arehomozygous
recessiveforthistrait.
Thisprovidesanotherexampleofatraitforwhichtherecessivealleleisfarmore
prevalentthanthedominantallele.

Lethaldominantallelesaremuchlesscommonthanlethalrecessives.
Ifalethaldominantkillsanoffspringbeforeitcanmatureandreproduce,theallelewill
notbepassedontofuturegenerations.
Incontrast,alethalrecessiveallelecanbepassedonbyheterozygouscarrierswhohave
normalphenotypes.

Alethaldominantallelecanescapeeliminationifitcausesdeathatarelativelyadvanced
age,aftertheindividualhasalreadypassedonthelethalalleletohisorherchildren.

OneexampleisHuntingtonsdisease,adegenerativediseaseofthenervoussystem.
Thedominantlethalallelehasnoobviousphenotypiceffectuntilanindividualisabout
35to45yearsold.
Thedeteriorationofthenervoussystemisirreversibleandinevitablyfatal.

AnychildborntoaparentwhohasthealleleforHuntingtonsdiseasehasa50%chance
ofinheritingthediseaseandthedisorder.

IntheUnitedStates,thisdevastatingdiseaseafflictsonein10,000people.

IG Lecture Outline 14-13

 Recently,moleculargeneticistshaveusedpedigreeanalysisofaffectedfamiliestotrack
theHuntingtonsalleletoalocusnearthetipofchromosome4.
ThishasledtothedevelopmentofatestthatcandetectthepresenceoftheHuntingtons
alleleinanindividualsgenome.
WhilesomediseasesareinheritedinasimpleMendelianfashionduetoallelesatasingle
locus,manyotherdisordershaveamultifactorialbasis.
Thesemayhaveageneticcomponentplusasignificantenvironmentalinfluence.
Multifactorialdisordersincludeheartdisease;diabetes;cancer;alcoholism;andcertain
mentalillnesses,suchasschizophreniaandmanicdepressivedisorder.
Thegeneticcomponentofsuchdisordersistypicallypolygenic.
Atpresent,littleisunderstoodaboutthegeneticcontributiontomostmultifactorial
diseases.
Thebestpublichealthstrategyiseducationaboutrelevantenvironmentalfactorsand
promotionofhealthybehavior.
3.Technologyisprovidingnewtoolsforgenetictestingandcounseling.

ApreventiveapproachtosimpleMendeliandisordersissometimespossible.

Theriskthataparticulargeneticdisorderwilloccurcansometimesbeassessedbeforea
childisconceivedorearlyinpregnancy.
Manyhospitalshavegeneticcounselorstoprovideinformationtoprospectiveparents
whoareconcernedaboutafamilyhistoryofaspecificdisease.
Considerahypotheticalcouple,JohnandCarol,whoareplanningtohavetheirfirst
child.
Inbothoftheirfamilieshistories,arecessivelethaldisorderispresent.BothJohnand
Carolhadbrotherswhodiedofthedisease.
WhilenotoneofJohn,Carol,ortheirparentshavethedisease,theirparentsmusthave
beencarriers(AaAa).
JohnandCaroleachhavea2/3chanceofbeingcarriersanda1/3chanceofbeing
homozygousdominant.
Theprobabilitythattheirfirstchildwillhavethediseaseis2/3(chancethatJohnisa
carrier)2/3(chancethatCarolisacarrier)1/4(chancethattheoffspringoftwo
carriersishomozygousrecessive)=1/9.
Iftheirfirstchildisbornwiththedisease,weknowthatJohnandCarolsgenotypemust
beAaandtheyarebothcarriers.
Inthatcase,thechancethattheirnextchildwillalsohavethediseaseis1/4.

Mendelslawsaresimplytherulesofprobabilityappliedtoheredity.
Becausechancehasnomemory,thegenotypeofeachchildisunaffectedbythe
genotypesofoldersiblings.
ThechancethatJohnandCarolsfirstthreechildrenwillhavethedisorderis1/41/4
1/4=1/64.Shouldthatoutcomehappen,thelikelihoodthatafourthchildwillalsohave
thedisorderisstill1/4.

Becausemostchildrenwithrecessivedisordersareborntoparentswithanormal
phenotype,thekeytoassessingriskisidentifyingwhetherprospectiveparentsarecarriersof
therecessivetrait.
Recentlydevelopedtestsforseveraldisorderscandistinguishnormalphenotypesin
heterozygotesfromhomozygousdominants.
IG Lecture Outline 14-14

Theseresultsallowindividualswithafamilyhistoryofageneticdisordertomake
informeddecisionsabouthavingchildren.
However,issuesofconfidentiality,discrimination,andcounselingmayarise.

Testsarealsoavailabletodetermineinuteroifachildhasaparticulardisorder.

Onetechnique,amniocentesis,canbeusedfromthe14thto16thweekofpregnancyto
assesswhetherthefetushasaspecificdisease.
Fetalcellsextractedfromamnioticfluidareculturedandkaryotypedtoidentifysome
disorders.
Otherdisorderscanbeidentifiedfromchemicalsintheamnioticfluids.
Asecondtechnique,chorionicvillussampling(CVS)allowsfasterkaryotypingandcan
beperformedasearlyastheeighthtotenthweekofpregnancy.
Thistechniqueextractsasampleoffetaltissuefromthechorionicvillioftheplacenta.
Thistechniqueisnotsuitablefortestsrequiringamnioticfluid.
Othertechniques,ultrasoundandfetoscopy,allowfetalhealthtobeassessedvisuallyin
utero.
Bothfetoscopyandamniocentesiscausecomplicationssuchasmaternalbleedingorfetal
deathinabout1%ofcases.
Therefore,thesetechniquesareusuallyreservedforcasesinwhichtheriskofagenetic
disorderorothertypeofbirthdefectisrelativelygreat.
Iffetaltestsrevealaseriousdisorder,theparentsfacethedifficultchoiceofterminating
thepregnancyorpreparingtocareforachildwithageneticdisorder.
Somegenetictraitscanbedetectedatbirthbysimpleteststhatarenowroutinely
performedinhospitals.
Onetestcandetectthepresenceofarecessivelyinheriteddisorder,phenylketonuria
(PKU).
Thisdisorderoccursinonein10,000to15,000births.
Individualswiththisdisorderaccumulatetheaminoacidphenylalanineanditsderivative
phenylpyruvateinthebloodtotoxiclevels.
Thisleadstomentalretardation.
Ifthedisorderisdetected,aspecialdietlowinphenylalanineusuallypromotesnormal
development.
Unfortunately,fewothergeneticdiseasesaresotreatable.

IG Lecture Outline 14-15