Test Bank For Human Genetics, 13th Edition All Chapters - 9781260240894.pdf

Test Bank For Human Genetics, 13th Edition All Chapters
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Lectureh1:h-hhhANSWERhh

-hDNAhishpackagedhashchromatin,hchromosomeshbecomehvisiblehduringhmitosis.h-
hhhANSWERhh




Homologues-h(maternalhandhpaternalhformshofhsamehchromosome)h-hhhANSWERhh

Meiosis:hG1,hS,hG2,hM.hBeforehreplicationhphase,hchromosomeshhavehonehchromatidha
ndhafterhreplication,hchromosomeshhaveh2hsisterhchromatids,hheldhtogetherhaththehcentr
omere.hEndshwithh4hdaughterhcellshwithh1hchromatidheach.h-hhhANSWERhh

Keyhdifferenceshfromhmitosis:hHomologshpairh(ProphasehI),hSisterhcentromereshacthasha
hsinglehcentromereh(MetaphasehI),hSisterhchromatidshremainhattachedh(AnaphasehI),hM

eiosishIhishahreductionhdivision-
hmeaninghstarthmeiosishIhwithh46hunitshandhendhmeiosishIhwithh23hunitsh(h2hchromatidshinh

eachhhaploidhdaughterhcells),hMeiosishIIhishanhequationalhdivisionh(identicalhtohmitosis).h-
hhhANSWERhh




RecombinationhoccurshinhProphasehI.hCrossinghoverhandhrecombhishExchangehofhhomo
logoushsegmentshbetweenhnon-sisterhchromatids.h-hhhANSWERhh

HomologueshmovehaparthduringhanaphasehI-
disjunction.h223hpossiblehcombinationshofhchromosomes.hInhcytokinesishI,hCellshdividehi
ntohtwohhaploidhdaughterhcells.hOnehcellhreceiveshmosthofhthehcytoplasmhandhthehotherh
becomeshthehfirsthpolarhbodyhwhichhdoesn'thgohthroughhMeiosishII.hMeiosishIhendshafterh
ovulation.hNonhdysjunctionhinhmeiosishI:hcanhcausehproblemshlikehTrisomyh21.h-
hhhANSWERhh




-
Briefhinterphasehbetweenhfirsthandhsecondhmeiotichdivisions.hNohShphasehoccurshinhMei
osishII.h-hhhANSWERhh

-
Inhthehsecondhmeiotichdivisionhahsecondhpolarhbodyhformshduringhoogenesis.hInhoogene
sis,hegghisharrestedhinhmetaphasehIIhuntilhfertilization.h-hhhANSWERhh

AfterhMeiosishtherehishahReductionhofhchromosomehnumberh2nn.h(diploidhvs.hhaploidhcel
ls)-
hNotationh'n'hhashtohdohwithhamounthofhDNAh(#of hnucleotides),hnoththehnecessarilyhtheh#h

ofhchromosomes.h-hhhANSWERhh

,Lectureh2:hPatternshofhInheritanceh-hhhANSWERhh

MedelianhInheritance-
hdeterminedhbyhahsingle hmajorhgene.hBasedhonhindependenthassortment.hDihybridhcros

sh(2hgenotypes)hwithhry,hRy,hrY,hRyhsethuphonhbothhsidesphenotypichratiohofh9:3:3:1-
yellowhround,hgreenhround,hyellowhwrinkled,hgreenhwrinkled,hIfhgeth9:3:3:1hyouhknowhtha
thsegregationhishindependent.h-hhhANSWERhh

Multifactorialhinheritance-multiplehgenetichandhnon-genetichfactorshinvolvedh-
hhhANSWERhh




Compoundhheterozygous:hhashtwohdifferenthmutanthalleleshforhahcharacterh-
hhhANSWERhh




Linkage-
2hgeneshphysicallyhnearheachhotherhonhahchromosomehwillhnothassorthrandomlyhinhmeio
sis.hTightlyhlinked:hwillhgeth2htypeshofhgameteshex.hPLhandhpl.hUnlinked:hwillhgeth4htypesh
ofhgameteshPL,hPl,hpL,hpl.h-hhhANSWERhh

Thehfrequencyhofhrecombinationhbetweenhtwohgeneshishproportionalhtohthehdistancehbet
weenhthehgenes.hThehcloserhthehgenesharehonhthehchromosomehthehlesshlikelyhcrossingh
overhoccurs.hLinkagehmap:h1%hrecombinationh=h1hmaphunith=h1hcentiMorganh(cM),hMap
hdistancesharehadditive.h-hhhANSWERhh




Thehnon-
randomhassociationhbetweenhalleleshathtwohlocationshonhahchromosomehishcalledhlinkag
ehdisequilibrium.hIfhthehfrequencyhofhchromosomeshwithhAB=Ab=aB=abhthenhthehgenes
harehinhequilibrium.hIfhfrequencyhofh1hallelehishseenhmoreh(AhmorehthanhBhforhex)hthenhge

nesharehinhlinkagehdisequilibrium.h-hhhANSWERhh

AutosomalhdominanthinheritancehExamples:h-hhhANSWERhh

Achondroplasia-
hFGFR3hmutations,hAlwayshfullhpenetrancehwithhachondroplasiah(sohnormalhparentshha

vehahchildhwithhaplasiahthenhit'shahnewhmutation).hHeterozygoushb/chhomozygoteshusual
lyhdiehinhuteroh-hhhANSWERhh

Neurofibromatosis-hNF1h(neurofibromin)handhNF2h(merlin)hmutations.h-hhhANSWERhh

Incompletehdominance-
hmixedhphenotype.hInhcaseshofhdisease,hDominanthdisordersharehmorehseverehinhhomoz

ygoteshthenhinhheterozygotesh(termedhalsoh"semidominant")hIe.hFamilialhHypercholeste
rolemia.h-hhhANSWERhh

Co-dominance-
hphenotypichexpressionhofhtwohdifferenthalleleshforhahlocushie.hBloodhtype.h-hhhANSWERhh




Autosomalhrecessivehinheritance:hExamples:hCystichfibrosis,hTay-
Sachshdisease,hSickle-cellhdiseaseh-hhhANSWERhh

,Pseudodominance:hthehinheritancehofhanhautosomalhrecessivehtraithmimicshanhautoso
malhdominanthpatternh-hhhANSWERhh

MalesharehhemizygoushwithhrespecthtohX-linkedhgenes.h-hhhANSWERhh

X-
linkedhdominanthinheritance:hAffectedhfemalesharehtwicehashcommonhashaffectedhmales
hbuthmaleshusuallyhmorehseverelyhaffectedhorhthehdisorderhmayhbehlethalhinhmalesh(Retth

syndrome).h-hhhANSWERhh

X-
linkedhrecessive:hincidencehishmuchhhigherhinhmaleshandhaffectedhmaleshdohnothusuallyh
transmiththehdisorderhunlesshmotherhishahcarrier.hHeterozygotehfemalesharehusuallyhuna
ffected,hbuthsomehmayhexpresshthehconditionhwithhvariablehseverityhashdeterminedhbyhth
ehpatternhofhXhinactivation.hAhsignificanthproportionhofhisolatedhcasesharehduehtohnewhmu
tationh(Duchennehmuscularhdystrophy-DMD).h-hhhANSWERhh

Pseudoautosomalhinheritance-
hgrouphofhgeneshonhthehinactivehxhchromosomeharehNOThinactivated.hDiseaseshassocia

tedhwithhthesehgenesharehinheritedhsimilarhtohautosomalhinheritance.h-hhhANSWERhh

SamehamounthofhX-
linkedhgenehproductshbetweenhmaleshandhfemaleshachievedhthroughhdosagehcompens
ation.hLyonhHypothesishstateshthaththehinactivehXhishNOThrandomlyhchosenhinheachhcellh
Ex.hAhstructurallyhabnormalhXhishpreferentiallyhinactivated.hInactivationhishNOThcomplet
e-
hsomehgeneshcanhescapehinactivationh(ie.hThosehwithhahfunctionalhhomologhonhthehY).hI

nactivationhishNOThpermanent-
hreversedhinhdevelopmenthofhgermhcellsh(nothpassedhonhtohgametes).h-hhhANSWERhh




ThehkeyhplayerhishthehX-
linkedhgenehXIST→hXh(inactive)hspecifichtranscript.hXISThishtranscribedhtohproducehahno
n-codinghRNAhthath"coats"hthehX-
chromosomehandhinactivateshit.hXISThishonlyhexpressedhfromhthehinactivehX.hThehhiston
eshonhthehcoatedhXhundergohmethylationhwhichhcauseshthehchromosomehtohcondenseh(
heterochromatin),hforminghahBarrhbody.h-hhhANSWERhh

-
SomehgeneshdohnothhavehYhhomologuehandhdohnothundergohinactivationh(e.g.hsteroidhs
ulfatasehgene)h-hhhANSWERhh

-Random/skewedhinactivationhmayhresulthinhaffected/totallyhhealthyhheterozygotes.h-
hhhANSWERhh




VariablehexpressionhofhX-
inactivation:hOnhbothhextremes,hahheterozygoushfemalehwithhrecessivehx-
linkedhdiseasehcouldhmanifesththehdisease.hInhahcasehwithhahdominanthX-
linkedhtrait,hinhwhichhalmosthallhofhahfemaleshXhchromosomeshwithhmutationhishinactive,h
mighthnothmanifesththishdisease.hIdenticalhtwinshcouldhevenhhavehdiffhphenotypeshdueht
ohskewedhXhinactivation.h-hhhANSWERhh

, Mosaicism-
hXhchromosomehinactivationhoccurshrandomlyhandhinactivationhpatternhishpassedhtohcellh

progeny.hResult:hfunctionalhmosaicismhinhwhichhfemalehishahmosaichwithhrespecthtohexp
ressionhofhgeneshonhXhchrom.hEx.hCalicohCat,hBh-hdominanthorange,hbh-
hrecessivehgenehblack,hGeneshforhwhite:hautosomal.h-hhhANSWERhh




GenetichHeterogeneityhcanhbehthehresulthofhLocushHeterogeneityh,hAllelichHeterogeneit
y,handhModifierhLoci.h-hhhANSWERhh

LocushHeterogeneity-
hahsinglehdisorder,htrait,horhpatternhofhtraitshcausedhbyhmutationshinhgeneshathdifferenthch

romosomalhloci.hEx.hretinitishpigmentosahhashautosomalhdominant,hautosomalhrecessiv
e,handhX-
linkedhorigins.hHowever,honlyhonehmutanthlocushishneededhforhthehphenotypehtohmanifes
th-hhhANSWERhh

Allelichheterogeneityh-
hManyhgenetichlocihpossesshmorehthanhonehmutanthallele.hInhthehCFTRhgene,hnearlyh14

00hmutationshfound.hSomehmutationshcausehclassicalhCFh+hpancreatichinsufficiencyh+hc
ongenitalhabsencehofhvashdeferens,hothershcausehlunghdiseasehwithhnormalhpancreatich
fxn.hOtherhcausehonlyhmalehsterility.h-hhhANSWERhh

Modifierhgene:hAhgenehthathaffectshthehphenotypichexpressionhofhanotherhgene.hSpecifi
challeleshofhonehorhmorehgenesh(modifierhgenes)hcanhsometimeshdramaticallyhmodifyhth
ehclinicalhseverityhofhthehphenotypehproducedhbyhmutationshinhahdisease-
causinghgene.Thishsourcehofhclinicalhheterogeneityhishoftenhreferredhtohashgenetichback
ground.hEx.hTwinshwithhthehsamehmutationhinhcystichfibrosishbuthonehishseverelyhsickhan
dhonehonlyhmoderatelyhsick-hexplainedhbyhmodifierhgenes.h-hhhANSWERhh

CandidatehlocihactinghashmodifiershforhCFTRhmutations:TGFB1h(cytokinehtransformingh
growthhfactorhbhandhMLB2h(Mannose-
bindinghlectin).hDifferenthalleleshofhthesehgeneshmodifyhthehseverityhofhCFh-hhhANSWERhh

Clinical/phenotypichheterogeneity:hmultiplehphenotypeshofhonehsinglehgenehex.hUSH2A
hgene,hcodeshforhproteinhimportanthinhdevelopmenthofhthehinnerhearhandhretina.hCanhbeh

blindhandhdeafh(typehIIhUsherhsyndrome)horhjusthblindh(RetinitishPigmentosa).h-
hhhANSWERhh




Otherhfactorshaffectionhphenotypehincludehenvironmentalhfactorshie.hG6PDhmutationhO
RhsoilhpHhandhhydrangeahcolor.hAlsohSex-
relatedhfactorshiehHemochromatosis,hAR,hcausedhbyhironhoverload,hishlesshcommonhinhf
emaleshduehtohlowerhironhintake/menstrualhironhloss.h-hhhANSWERhh

G6PDh(glucose-6-phosphatehdehydrogenase)hDeficiencyh(X-linked)-
hCanhleadhtohhemolytichanemia,hmanyhpplhwithhthishdisorderhneverhexperiencehanyhsym

ptoms.hHemolytichanemiahcanhbehtriggeredhbyhenvironmentalhfactorshsuchhashbacterial/
viralhinfections,hdrugh(sulfa,hmalariahmedications),heatinghfavahbeanshorhinhalinghfavahb
eanhplanthpollen.h-hhhANSWERhh