Test Bank for Medical Genetics 5th Edition by Jorde - Ch. 1-8, 9780323188357, with Rationales

Test Bank For Human Genetics, 13th Edition All Chapters -
s s s s s s s s s




Lectures1:s-sssANSWERss

-sDNAsisspackagedsasschromatin,schromosomessbecomesvisiblesduringsmitosis.s-
sssANSWERss




Homologues-s(maternalsandspaternalsformssofssameschromosome)s-sssANSWERss

Meiosis:sG1,sS,sG2,sM.sBeforesreplicationsphase,schromosomesshavesoneschromatidsan
dsaftersreplication,schromosomesshaves2ssisterschromatids,sheldstogethersatsthescentro
mere.sEndsswiths4sdaughterscellsswiths1schromatidseach.s-sssANSWERss

Keysdifferencessfromsmitosis:sHomologsspairs(ProphasesI),sSisterscentromeressactsassas
singlescentromeres(MetaphasesI),sSisterschromatidssremainsattacheds(AnaphasesI),sMei
osissIsissasreductionsdivision-
smeaningsstartsmeiosissIswiths46sunitssandsendsmeiosissIswiths23sunitss(s2schromatidssinse

achshaploidsdaughterscells),sMeiosissIIsissansequationalsdivisions(identicalstosmitosis).s-
sssANSWERss




RecombinationsoccurssinsProphasesI.sCrossingsoversandsrecombsissExchangesofshomol
ogousssegmentssbetweensnon-sisterschromatids.s-sssANSWERss

HomologuessmovesapartsduringsanaphasesI-
disjunction.s223spossiblescombinationssofschromosomes.sInscytokinesissI,sCellssdividesi
ntostwoshaploidsdaughterscells.sOnescellsreceivessmostsofsthescytoplasmsandsthesothersb
ecomessthesfirstspolarsbodyswhichsdoesn'tsgosthroughsMeiosissII.sMeiosissIsendssaftersov
ulation.sNonsdysjunctionsinsmeiosissI:scanscausesproblemsslikesTrisomys21.s-
sssANSWERss




-
Briefsinterphasesbetweensfirstsandssecondsmeioticsdivisions.sNosSsphasesoccurssinsMeio
sissII.s-sssANSWERss

-
Insthessecondsmeioticsdivisionsassecondspolarsbodysformssduringsoogenesis.sInsoogene
sis,seggsissarrestedsinsmetaphasesIIsuntilsfertilization.s-sssANSWERss

AftersMeiosisstheresissasReductionsofschromosomesnumbers2nn.s(diploidsvs.shaploidscell
s)-
sNotations'n'shasstosdoswithsamountsofsDNAs(#of snucleotides),snotsthesnecessarilysthes#so

fschromosomes.s-sssANSWERss

Lectures2:sPatternssofsInheritances-sssANSWERss

,MedeliansInheritance-
sdeterminedsbysa ssinglesmajorsgene.sBasedsonsindependentsassortment.sDihybridscross

s(2 sgenotypes)swithsry, sRy,srY,sRyssetsupsonsbothssidesphenotypicsratiosof s9:3:3:1-

yellowsround,sgreensround,syellowswrinkled,sgreenswrinkled,sIfsgets9:3:3:1syousknowsthat
ssegregationsissindependent.s-sssANSWERss




Multifactorialsinheritance-multiplesgeneticsandsnon-geneticsfactorssinvolveds-
sssANSWERss




Compoundsheterozygous:shasstwosdifferentsmutantsallelessforsascharacters-sssANSWERss

Linkage-
2sgenessphysicallysnearseachsothersonsaschromosomeswillsnotsassortsrandomlysinsmeios
is.sTightlyslinked:swillsgets2stypessofsgametessex.sPLsandspl.sUnlinked:swillsgets4stypessofs
gametessPL,sPl,spL,spl.s-sssANSWERss

Thesfrequencysofsrecombinationsbetweenstwosgenessissproportionalstosthesdistancesbet
weensthesgenes.sThesclosersthesgenessaresonstheschromosomestheslessslikelyscrossings
oversoccurs.sLinkagesmap:s1%srecombinations=s1smapsunits=s1scentiMorgans(cM),sMaps
distancessaresadditive.s-sssANSWERss

Thesnon-
randomsassociationsbetweensallelessatstwoslocationssonsaschromosomesisscalledslinkag
esdisequilibrium.sIfsthesfrequencysofschromosomesswithsAB=Ab=aB=absthensthesgeness
aresinsequilibrium.sIfsfrequencysofs1sallelesissseensmores(AsmoresthansBsforsex)sthensgene
ssaresinslinkagesdisequilibrium.s-sssANSWERss

AutosomalsdominantsinheritancesExamples:s-sssANSWERss

Achondroplasia-
sFGFR3smutations,sAlwayssfullspenetranceswithsachondroplasias(sosnormalsparentsshav

esaschildswithsaplasiasthensit'ssasnewsmutation).sHeterozygoussb/cshomozygotessusuallys
diesinsuteros-sssANSWERss

Neurofibromatosis-sNF1s(neurofibromin)sandsNF2s(merlin)smutations.s-sssANSWERss

Incompletesdominance-
smixedsphenotype.sInscasessofsdisease,sDominantsdisorderssaresmoresseveresin shomoz

ygotessthensinsheterozygotess(termedsalsos"semidominant")sIe.sFamilialsHypercholeste
rolemia.s-sssANSWERss

Co-dominance-
sphenotypicsexpressionsofstwo sdifferentsallelessforsaslocussie.sBloodstype.s-sssANSWERss




Autosomalsrecessivesinheritance:sExamples:sCysticsfibrosis,sTay-
Sachssdisease,sSickle-cellsdiseases-sssANSWERss

Pseudodominance:sthesinheritancesofsansautosomalsrecessivestraitsmimicssansautosom
alsdominantspatterns-sssANSWERss

,MalessareshemizygousswithsrespectstosX-linkedsgenes.s-sssANSWERss

X-
linkedsdominantsinheritance:sAffectedsfemalessarestwicesasscommonsassaffectedsmaless
butsmalessusuallysmoresseverelysaffectedsorsthesdisordersmaysbeslethalsinsmaless(Rettss
yndrome).s-sssANSWERss

X-
linkedsrecessive:sincidencesissmuchshighersinsmalessandsaffectedsmalessdosnotsusuallyst
ransmitsthesdisordersunlesssmothersissascarrier.sHeterozygotesfemalessaresusuallysunaff
ected,sbutssomesmaysexpresssthesconditionswithsvariablesseveritysassdeterminedsbysthes
patternsofsXsinactivation.sAssignificantsproportionsofsisolatedscasessaresduestosnewsmutat
ions(Duchennesmuscularsdystrophy-DMD).s-sssANSWERss

Pseudoautosomalsinheritance-
sgroupsofsgenessonsthesinactivesxschromosomesaresNOTsinactivated.sDiseasessassociat

edswithsthesesgenessaresinheritedssimilarstosautosomalsinheritance.s-sssANSWERss

SamesamountsofsX-
linkedsgenesproductssbetweensmalessandsfemalessachievedsthroughsdosagescompens
ation.sLyonsHypothesissstatessthatsthesinactivesXsissNOTsrandomlyschosensinseachscells
Ex.sAsstructurallysabnormalsXsisspreferentiallysinactivated.sInactivationsissNOTscomplete
-
ssomesgenesscansescapesinactivations(ie.sThoseswithsa sfunctionalshomologsonsthesY).sIn

activationsissNOTspermanent-
sreversedsinsdevelopmentsofsgermscellss(notspassedsonstosgametes).s-sssANSWERss




TheskeysplayersissthesX-
linkedsgenesXIST→sXs(inactive)sspecificstranscript.sXISTsisstranscribedstosproducesasno
n-codingsRNAsthats"coats"sthesX-
chromosomesandsinactivatessit.sXISTsissonlysexpressedsfromsthesinactivesX.sTheshiston
essonsthescoatedsXsundergosmethylationswhichscausesstheschromosomestoscondenses(
heterochromatin),sformingsasBarrsbody.s-sssANSWERss

-
SomesgenessdosnotshavesYshomologuesandsdosnotsundergosinactivations(e.g.ssteroidssu
lfatasesgene)s-sssANSWERss

-Random/skewedsinactivationsmaysresultsinsaffected/totallyshealthysheterozygotes.s-
sssANSWERss




VariablesexpressionsofsX-
inactivation:sOnsbothsextremes,sasheterozygoussfemaleswithsrecessivesx-
linkedsdiseasescouldsmanifeststhesdisease.sInsascaseswithsasdominantsX-
linkedstrait,sinswhichsalmostsallsofsasfemalessXschromosomesswithsmutationsissinactive,s
mightsnotsmanifeststhissdisease.sIdenticalstwinsscouldsevenshavesdiffsphenotypessduestos
skewedsXsinactivation.s-sssANSWERss

Mosaicism-
sXschromosomesinactivationsoccurssrandomlysandsinactivationspatternsisspassedstoscells

, progeny.sResult:sfunctionalsmosaicismsinswhichsfemalesissasmosaicswithsrespectstosexpr
essionsofsgenessonsXschrom.sEx.sCalicosCat,sBs-sdominantsorange,sbs-
srecessivesgenesblack,sGenessforswhite:sautosomal.s-sssANSWERss




GeneticsHeterogeneityscansbesthesresultsofsLocussHeterogeneitys,sAllelicsHeterogeneity
,sandsModifiersLoci.s-sssANSWERss

LocussHeterogeneity-
sassinglesdisorder,strait, sorspatternsofstraitsscausedsbysmutationssinsgenessatsdifferentschr

omosomalsloci.sEx.sretinitisspigmentosashassautosomalsdominant,sautosomalsrecessive
,sandsX-
linkedsorigins.sHowever,sonlysonesmutantslocussissneededsforsthesphenotypestosmanifest
s-sssANSWERss




Allelicsheterogeneitys-
sManysgeneticslocispossesssmoresthansonesmutantsallele.sInsthesCFTRsgene,snearlys140

0smutationssfound.sSomesmutationsscausesclassicalsCFs+spancreaticsinsufficiencys+sco
ngenitalsabsencesofsvassdeferens,sothersscauseslungsdiseaseswithsnormalspancreaticsfx
n.sOtherscausesonlysmalessterility.s-sssANSWERss

Modifiersgene:sAsgenesthatsaffectssthesphenotypicsexpressionsofsanothersgene.sSpecifics
allelessofsonesorsmoresgeness(modifiersgenes)scanssometimessdramaticallysmodifysthesc
linicalsseveritysofsthesphenotypesproducedsbysmutationssinsasdisease-
causingsgene.Thisssourcesofsclinicalsheterogeneitysissoftensreferredstosassgeneticsbackg
round.sEx.sTwinsswithsthessamesmutationsinscysticsfibrosissbutsonesissseverelyssicksandso
nesonlysmoderatelyssick-sexplainedsbysmodifiersgenes.s-sssANSWERss

CandidateslocisactingsassmodifierssforsCFTRsmutations:TGFB1s(cytokinestransformings
growthsfactorsbsandsMLB2s(Mannose-
bindingslectin).sDifferentsallelessofsthesesgenessmodifysthesseveritysofsCFs-sssANSWERss

Clinical/phenotypicsheterogeneity:smultiplesphenotypessofsonessinglesgenesex.sUSH2As
gene,scodessforsproteinsimportantsinsdevelopmentsofsthesinnersearsandsretina.sCansbesbli
ndsandsdeafs(typesIIsUsherssyndrome)sorsjustsblinds(RetinitissPigmentosa).s-sssANSWERss

Othersfactorssaffectionsphenotypesincludesenvironmentalsfactorssie.sG6PDsmutationsOR
ssoilspHsandshydrangeascolor.sAlsosSex-

relatedsfactorssiesHemochromatosis,sAR,scausedsbysironsoverload,sisslessscommonsinsfe
malessduestoslowersironsintake/menstrualsironsloss.s-sssANSWERss

G6PDs(glucose-6-phosphatesdehydrogenase)sDeficiencys(X-linked)-
sCansleadstoshemolytic sanemia,smanyspplswithsthissdisordersneversexperiencesanyssymp

toms.sHemolyticsanemiascansbestriggeredsbysenvironmentalsfactorsssuchsassbacterial/vi
ralsinfections,sdrugs(sulfa,smalariasmedications),seatingsfavasbeanssorsinhalingsfavasbea
nsplantspollen.s-sssANSWERss

Penetrance-
sproportionsofsindividualsswith sasspecificsgenotypesandsactuallysmanifeststhesphenotype.

sEx.sSplit-