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MCQsFORSTUDENTS
1.A28yearoldhealthyfemalemedicalstudent,whosefatherhadbeendiagnosedwithAdultpolycystickidney
disease(ADPKD),hadultrasoundscandoneonhertwokidneys,whichsheinquisitivelyrequestedduringa
radiologypostingandwasnormal.AweeklatersheagainrequestedforanMRI,andaT2weightedbreathheld
AdetectatruncatingmutationinthePKD2genein
MRIwithoutcontrastinjectioninonebreathholdandthisrevealedmultipletinycysts(>10/kidney)inacortical
herandherotheraffectedfamilymembers.
andperihilardistribution.DNAtestingwillmostlikely:
BdetectcontiguousdeletionofPKD1/TSC2with
resultantendstagerenaldisease.
CdetectatruncatingmutationinthePKDH1gene
abnormality.EdetectatruncatingmutationinthePKD1geneonchromosome4q21inherandherfather
2.WhichofthefollowingistrueconcerningthepathogenesisofAdultpolycystickidneydisease(ADPKD)?
AADPKDischaracterizedbynumerouscystswithintherenalcalycealsystemBMutationsofPKHD1resultin
ADPKD,pancreaticcystsandhepaticbiliarydysgenesisandfibrosis.CThecystsfluidsoriginateinmorethan
98%ofnephrons,andmostlyderivedfromglomerularfiltrate.
D.defectsinthegeneproduct,polycystin1andpolycystin2,presentintheciliaoftubularepitheliacellsdisrupt
calciumsignalingthatnormallyinhibitsrenaltubulegrowth.Edefectsinthegeneproduct,fibrocystin,foundin
thekidney,liverandpancreas,appearstobeinvolvedintheregulationofcellproliferationandadhesion
3.TheprocessofDNAsynthesisnormallyavoidstransmittingerrorstosubsequentgenerationsofcells.However,
geneticabnormalitiesofDNAmismatch/repairdooccur,andincludeallofthefollowing,except:AADPKDB
hereditarynonpolyposiscoloncancer(HNPCC)CataxiatelangiectasiaDBloomsyndromeExeroderma
pigmentosum
4.Whichofthefollowingistheleastcommoncauseofendstagerenaldisease?
AAdultpolycystickidneydiseaseBDiabetesmellitusCHypertensionDTheyallcauseESRDwithaboutthe
samefrequencyEUnknownduetocurrentlackofclinicaldata
5.Whichofthefollowingisnottrueconcerningtheanatomyofthegene?
A.AgeneproductcanoccasionallyconsistofRNAthatisnottranslated.
B.ExonsrefertotheportionofgenesthatareeventuallysplicedtogethertoformmRNA.
C.IntronsrefertothespacingregionsbetweentheexonsthataresplicedoutofprecursorRNAsduring
RNAprocessing
D.GenetranscriptionoccurswhenRNApolymerasebeginstosynthesizeRNAfromtheDNAtemplate.
E.Mutationsoccuronlyincertaindomainsofageneandpointmutationsthatintroduceaprematurestop
codonresultinanaminoacidsubstitutionifthecodonisaltered.
6.A25yearsold,otherwisehealthymale,hasbeenselectedasapotentialkidneydonor.The55yearsold
fatherhasa10yearshistoryofADPKDwithESRD.Priortothekidneytransplant,ageneticcounseling
anddirectmutationanalysisformoleculardiagnosisofADPKDinthe25yearsoldkidneydonorwas
scheduledtobeperformed.WhichofthefollowingfactsaboutDNAsequencingistrueexcept:
A.Itiscompletelyanautomatedprocedure,withtheadvantageofusingabloodsamplefromthedonor.
B.ThecapillaryelectrophoresisbasedSangermethodinwhichdideoxynucleotidesareusedtorandomlyterminate
DNApolymerizationateachofthefourbases(A,G,T,C)iscurrentlythemostcommonlyusedstrategy.
C.Theuseoffluorescentlylabeleddideoxynucleotidesallowsdetectionofthedifferentbasesanddirect
computeranalysisoftheDNAsequence.
D.NewerDNAsequencingtechnologies,suchaspyrosequencingchemistries;wholegenomesequencingusing
solidphasesequencing;massspectrometryandDNAchipsarelaboriouslesscosteffective
E.ThemajorlimitationofdirectDNAtestingisthatdefinitivediseaseassociatedmutationdarefoundinonly
about4060%ofcase.
7.Allthefollowinginformationconcerningtheanatomyoflocus,allelesandagene,aretrue,except:
A.Theparticularallelewhichcausesthecharacteristicofanindividualtobeexpressedinanormalfashionis
oftenreferredtoasthewildtypeallele.
B.IfamaleinheritsarecessivemutantallelesuchascolorblindnessonhisXchromosome,heexpresses
colorblindnessbecausehepossessesthewildtypealleleonhisYchromosome.
C.Therearetwochromosomesofeachkindandhencetwoallelesofeachkindofgene,exceptforthesex
chromosomes,whichissaidtobehemizygousforallelescarriedonthemalesXchromosome.
D.Analleleisanyoneoftwoormorealternativeformsofagenethatoccupiesafixedpositioninthe
chromosome.
E. A locus is the specific position of a particular gene or one of its alleles, in all homologous
chromosomes.
8.TechnicaladvancesinDNAsequencingandcomputationalbioinformaticshaveledtothecompletionofthe
DNAsequenceforthehumanchromosomes.WhichofthefollowingistrueconcerningtheHumanGenome
Project(HGP)anditscurrentdevelopments?
A.Thewholegenomesofotherorganismsareyettobesequencedcompletely.
B.HGPisyettocommencecomparativegenomics.
C.StudiesoflargescaleexpressionofRNAs(functionalgenomics)andproteins(proteomics)candetect
differencesbetweenvarioustissuesinhealthanddisease.
D.EfforttoexamineethicalandlegalimplicationsoftheHGPhasnotyetbeeninitiated.
E.HGPisyettoidentifygenesthatplaycriticalrolesinthedevelopmentofpolygenicandmultifactorial
disorders.
9.WhichofthefollowingstatementsareNOTTRUEconcerningmutationsandthetransmissionofgenetic
diseases:
A.ItisachangeintheprimarynucleotidesequenceofDNAregardlessofitsfunctionalconsequencesand
canoccurinthegermline(spermoroocytes)duringembryogenesisorinsomatictissues.
B.Somaticmutationsareassociatedwithneoplasiabecausetheyconferagrowthadvantagetocells.
C.Epigeneticeventsareheritablechangesthatdonotinvolvechangesingenesequence(e.g.,alteredDNA
methylation),therefore,donotinfluencegeneexpressionorgeneticdamage.
D.Mutationsareusuallystable,withtheexceptionoftripletnucleotiderepeats.
E.Ifapurineisreplacedbyanotherpurinebase(A G),thesubstitutioniscalledatransitions;ontheother
handifapurineisreplacedbypyrimidineitisreferredtoastransversions.
10.Anewlyweddedcouplecomesintoyourclinicaftertheirhoneymoonandstatesthattheyareplanningtohave
achildsoon.Themanis60yearsoldandthewomanis34yearsold.Themangaveafamilyhistoryof
achondrodysplasia,whilethewomangaveafamilyhistoryofneurofibromatosis.Theywerebothconcerned
abouttheriskoftransmittinganygeneticdiseasetotheirchildandcameinforgeneticcounselingandyour
mostlikelyresponsewouldincludeallofthefollowingEXCEPT:
A.Mutationratesaredifficulttodetermineinhumansbecausemanymutationsaresilentandbecause
testingisoftennotadequatetodetectthephenotypicconsequences.
B.Theprobabilityofacquiringnewpointmutationsismuchgreaterinthefemalegermlinethanthemale
germline,inwhichratesofaneuploidyareincreased.
C.Theincidenceofachondrodysplasia,Marfansyndromeandneurofibromatosisasaresultofnewpoint
mutationsinspermatogoniaincreaseswithpaternalage
D.Itisestimatedthatabout1in10spermcarriesanewdeleteriousmutation.
E.TheratesfornewmutationsarecalculatedforautosomaldominantandXlinkeddisordersandare~105
106/locuspergenerationandthereforenewmutationcanbetransmittedtotheaffectedindividualbutdoes
notnecessarilyimplythattheparentsareatrisktotransmitthediseasetootherchildren.
MATCHING:PARTA
A. PraderWilli syndrome (neonatal hypotonia, developmental delay, obesity, short stature, and
hypogonadism)
B.Marfansyndrome
C.Huntingtondisease
D.Singlenucleotidepolymorphisms(SNPs)
E.ADPKDcausedbyPKD2genemutation
F.FragileXsyndrome
G.Promyelocyticleukemia.
Regulationofgeneexpressionisinfluencedbyepigeneticevents,suchasgeneticimprinting,whichisa
processesinwhichDNAmethylationorhistonemodificationsisassociatedwithgenesilencing.
Thisclassofmutationconsistsofdeletionsorinsertionsthatshiftthereadingframeofthemessage
ThisclassofmutationconsistsoftrinucleotiderepeatsrepeatsthatencodesFMR1protein.
Thet(15;17)chromosomaltranslocationfusesthePMLgenetoaportionoftheretinoicacidreceptor
(RAR)gene.
AnautosomaldominantdisordercausedbyexpansionofaCAGtrinucleotiderepeatthatencodesa
polyglutaminetract.
Characterization,usingDNAchips,providesimportanttoolforcomprehensiveanalysesofgeneticvariation,
whichmaybeusefulpharmacogenomicsandpredictionofdiseasepredilection.
AngiotensinIIreceptorblockersmayslowdiseaseprogression,asdemonstratedbythehumangenomeProject.
MATCHING:PARTB
A.Frameshiftmutation
B.Missensemutation
C.synonymouspolymorphism
D.pointmutations
E.Geneconversion
F.nonsynonymouspolymorphism
G.Nonsensemutation
H.Gainoffunctionmutations
I.Inactivatingmutations
J.Haploinsufficiency
1. Mutationsinvolvingsinglenucleotides
2. DNAsequencechangethatoccursinacodingregionandtherebyaltersanaminoacidsequence
3. DNAsequencevariationsthatdonotresultinaperceptiblephenotypeandconsistofsinglebasepair
substitutionsthatdonotaltertheproteincodingsequencebecauseofthedegeneratenatureofthegeneticcode
4. Smallnucleotidedeletionsorinsertionsthatcauseashiftofthecodonreadingframe
5. SequencevariationsthataltermRNAstability,translation,oraminoacidsequence,butdonotresultina
perceptiblephenotype.
6. Readingframealterationsthatresultinanabnormalproteinsegmentofvariablelengthbeforeterminationof
translationoccursatastopcodon
7. Nonreciprocalexchangeofhomologousgeneticinformation,usedtoexplainhowaninternalportionofagene
isreplacedbyahomologoussegmentcopiedfromanotheralleleorlocus.
8. Mutationinasinglealleleinandwhichonenormalalleleisnotcapableofmaintaininganormalphenotype,
seeninVonHippelLindausyndromeandotherdiseasesassociatedwithmutationsintranscriptionfactors.
9. Mutationistypicallydominant,andresultsinphenotypicalterationswhenasinglealleleisaffected.
10. Mutationistypicallyrecessive,andtheaffectedindividualiseitherhomozygousorcompoundheterozygous
forthediseasecausingmutations.
ANSWERS
#1,ANSWER=A:
AdetectatruncatingmutationinthePKD2geneinherandherotheraffectedfamilymembers.Bdetect
contiguousdeletionofPKD1/TSC2withresultantendstagerenaldisease:thisisseenintuberoussclerosis.
CdetectatruncatingmutationinthePKDH1geneonchromosome6p21inherandherfather:thisisseen
inARPKD.DdetectatruncatingmutationintheMCKD1geneonchromosome1q21,asthecauseofher
abnormality:thisisseeninmedullarycystickidneydisease.EdetectatruncatingmutationinthePKD1
geneonchromosome4q21inherandherfather:amutationinthePKD1geneisseenonchromosome16p.
2.WhichofthefollowingistrueconcerningthepathogenesisofAdultpolycystickidneydisease
(ADPKD)?
ANSWER=D
AADPKDischaracterizedbynumerouscystswithintherenalcalycealsystem.INCORRECT:ADPKDis
characterizedbycystswithintherenalparenchyma.BothADPKDandARPKDlackcystswithintherenal
calycealsystem.BMutationsofPKHD1resultinADPKD,pancreaticcystsandhepaticbiliarydysgenesis
andfibrosis.INCORRECT:MutationsofPKHD1resultinARPKD,pancreaticcystsandhepaticbiliary
dysgenesisandfibrosis.CThecystsfluidsoriginateinmorethan98%ofnephrons,andmostlyderived
fromglomerularfiltrate.INCORRECT:Thecystsfluidsoriginateinabout2%ofnephrons,andinitially
derivedfromglomerularfiltrate,butmostlyderivedfromtransepitheliamovement.
D.CORRECT:defectsinthegeneproduct,polycystin1andpolycystin2,presentintheciliaoftubular
epitheliacellsdisruptcalciumsignalingthatnormallyinhibitsrenaltubulegrowth.Edefectsinthegene
product,fibrocystin,foundinthekidney,liverandpancreas,appearstobeinvolvedintheregulationofcell
proliferationandadhesion.INCORRECT:defectsinthegeneproduct,fibrocystin,foundinthekidney,
liverandpancreas,appearstobeinvolvedintheregulationofcellproliferationandadhesioninARPKD.
3.TheprocessofDNAsynthesisnormallyavoidstransmittingerrorstosubsequentgenerationsofcells.
However,geneticabnormalitiesofDNAmismatch/repairdooccur,andincludeallofthefollowing,except:
ANSWER:A
AADPKDBhereditarynonpolyposiscoloncancer(HNPCC)CataxiatelangiectasiaDBloomsyndromeE
xerodermapigmentosum
4.Whichofthefollowingistheleastcommoncauseofendstagerenaldisease?
ANSWER:A
AAdultpolycystickidneydiseaseBDiabetesmellitusCHypertensionDTheyallcauseESRDwithabout
thesamefrequencyEUnknownduetocurrentlackofclinicaldata
5.Whichofthefollowingisnottrueconcerningtheanatomyofthegene?
ANSWER:E.Mutationsoccurinalldomainsofageneandpointmutationsthatintroduceapremature
stopcodonresultnoaminoacidformation.
A.AgeneproductcanoccasionallyconsistofRNAthatisnottranslated.
B.ExonsrefertotheportionofgenesthatareeventuallysplicedtogethertoformmRNA.
C.IntronsrefertothespacingregionsbetweentheexonsthataresplicedoutofprecursorRNAs
duringRNAprocessing
D.GenetranscriptionoccurswhenRNApolymerasebeginstosynthesizeRNAfromtheDNA
template.
E.Mutationsoccuronlyincertaindomainsofageneandpointmutationsthatintroducea
prematurestopcodonresultinanaminoacidsubstitutionifthecodonisaltered.
6.ThefollowingfactsaboutDNAsequencingistrueexcept:
ANSWER:DNewerDNAsequencingtechnologies,suchaspyrosequencingchemistries;wholegenome
sequencingusingsolidphasesequencing;massspectrometryandDNAchipsarefasterandmorecost
effective.
A.Itiscompletelyanautomatedprocedure.
B.ThecapillaryelectrophoresisbasedSangermethodinwhichdideoxynucleotidesareusedtorandomly
terminateDNApolymerizationateachofthefourbases(A,G,T,C)iscurrentlythemostcommonlyused
strategy.
C.Theuseoffluorescentlylabeleddideoxynucleotidesallowsdetectionofthedifferentbasesanddirect
computeranalysisoftheDNAsequence.
D.NewerDNAsequencingtechnologies,suchaspyrosequencingchemistries;wholegenomesequencing
usingsolidphasesequencing;massspectrometryandDNAchipsarelaboriouslesscosteffective
E.ItispossibletodeducetheDNAsequencebyexaminingtheprogressionoffragmentlengthsgeneratedin
eachofthefournucleotidereactions,afterseparatingthearrayofterminatedDNAfragmentsusinghigh
resolutiongelorcapillaryelectrophoresis.
7.Allthefollowinginformationconcerningtheanatomyoflocus,allelesandagene,aretrue,except:
ANSWER=B
A.Theparticularallelewhichcausesthecharacteristicofanindividualtobeexpressedinanormal
fashionisoftenreferredtoasthewildtypeallele.
B.IfamaleinheritsarecessivemutantallelesuchascolorblindnessonhisXchromosome,heexpresses
colorblindnessbecausehepossessesthewildtypealleleonhisYchromosome:Ifamaleinheritsarecessive
mutantallelesuchascolorblindnessonhisXchromosome,heexpressescolorblindnessbecausehelacks
thewildtypealleleonhisYchromosome.
C.Therearetwochromosomesofeachkindandhencetwoallelesofeachkindofgene,exceptforthesex
chromosomes,whichissaidtobehemizygousforallelescarriedonthemalesXchromosome.
D.Analleleisanyoneoftwoormorealternativeformsofagenethatoccupiesafixedpositioninthe
chromosome.
E.Alocusisthespecificpositionofaparticulargeneoroneofitsalleles,inallhomologous
chromosomes.
8. TechnicaladvancesinDNAsequencingandcomputationalbioinformaticshaveledtothecompletionof
theDNAsequenceforthehumanchromosomes.WhichofthefollowingistrueconcerningtheHuman
GenomeProject(HGP)anditscurrentdevelopments?
ANSWER=C
A.Inadditiontothehumangenome,thewholegenomesofsomeorganismshavebeensequenced
partiallyorcompletely.
B.Therehavebeenadvancementsincomparativegenomics
C.TherehavebeenadvancementsinstudyoflargescaleexpressionofRNAs(functionalgenomics)and
proteins(proteomics)inordertodetectdifferencesbetweenvarioustissuesinhealthanddisease.
D.EfforttoexamineethicalandlegalimplicationsoftheHGPhavebeeninitiated
E.HGPhashelpedintheidentificationofgenesthatplaycriticalrolesinthedevelopmentofpolygenicand
multifactorialdisorders.
9.WhichofthefollowingstatementsareNOTTRUEconcerningmutationsandthe
transmissionofgeneticdiseases:
ANSWER:C
A.ItisachangeintheprimarynucleotidesequenceofDNAregardlessofitsfunctional
consequencesandcanoccurinthegermline(spermoroocytes)duringembryogenesisorin
somatictissues.
B.Somaticmutationsareassociatedwithneoplasiabecausetheyconferagrowthadvantage
tocells.
C.Epigeneticeventsareheritablechangesthatdonotinvolvechangesingenesequence(e.g.,altered
DNAmethylation),therefore,donotinfluencegeneexpressionorgeneticdamage:
ANSWER:C
Epigeneticeventsareheritablechangesthatdonotinvolvechangesingenesequence(e.g.,
alteredDNAmethylation),anditmayinfluencegeneexpressionorgeneticdamage.
D.Mutationsareusuallystable,withtheexceptionoftripletnucleotiderepeats.
Ifapurineisreplacedbyanotherpurinebase(A G),thesubstitutioniscalledatransitions;ontheother
handifapurineisreplacedbypyrimidineitisreferredtoastransversion
10.Anewlyweddedcouplecomeintoyourclinicaftertheirhoneymoonandstatesthattheyareplanningto
haveachildsoon.Themanis60yearsoldandthewomanis34yearsold.Themangaveafamilyhistoryof
achondrodysplasia,whilethewomangaveafamilyhistoryofneurofibromatosis.Theywerebothconcerned
abouttheriskoftransmittinganygeneticdiseasetotheirchildandcameinforgeneticcounselingandyour
mostlikelyresponsewouldincludeallofthefollowingEXCEPT:
ANSWER:B
A.Mutationratesaredifficulttodetermineinhumansbecausemanymutationsaresilentandbecause
testingisoftennotadequatetodetectthephenotypicconsequences.
B.Theprobabilityofacquiringnewpointmutationsismuchgreaterinthefemalegermlinethanthemale
germline,inwhichratesofaneuploidyareincreased:ANSWERB:Theprobabilityofacquiringnewpoint
mutationsismuchgreaterinthemalegermlinethanthefemalegermline,inwhichratesofaneuploidyare
increased.
C.Theincidenceofachondrodysplasia,Marfansyndromeandneurofibromatosisasaresultofnewpoint
mutationsinspermatogoniaincreaseswithpaternalage
D.Itisestimatedthatabout1in10spermcarriesanewdeleteriousmutation.
E.TheratesfornewmutationsarecalculatedforautosomaldominantandXlinkeddisordersandare~10
5106/locuspergenerationandthereforenewmutationcanbetransmittedtotheaffectedindividualbut
doesnotnecessarilyimplythattheparentsareatrisktotransmitthediseasetootherchildren.
MATCHING:PARTA_ANSWERS
A. PraderWilli syndrome (neonatal hypotonia, developmental delay, obesity, short stature, and
hypogonadism)
B.Marfansyndrome
C.Huntingtondisease
D.Singlenucleotidepolymorphisms(SNPs)
E.ADPKDcausedbyPKD2genemutation
F.FragileXsyndrome
G.Promyelocyticleukemia.
A.Regulationofgeneexpressionisinfluencedbyepigeneticevents,suchasgeneticimprinting,whichis
aprocessesinwhichDNAmethylationorhistonemodificationsisassociatedwithgenesilencing.
E.Thisclassofmutationconsistsofdeletionsorinsertionsthatshiftthereadingframeofthemessage
F.ThisclassofmutationconsistsofCGGtrinucleotiderepeatsthatencodesFMR1protein.
G.Thet(15;17)chromosomaltranslocationfusesthePMLgenetoaportionoftheretinoicacidreceptor
(RAR)gene..
C.AnautosomaldominantdisordercausedbyexpansionofaCAGtrinucleotiderepeatthatencodesa
polyglutaminetract.
D.Characterization,usingDNAchips,providesimportanttoolforcomprehensiveanalysesofgenetic
variation,whichmaybeusefulpharmacogenomicsandpredictionofdiseasepredilection.
B.AngiotensinIIreceptorblockersmayslowdiseaseprogression,asdemonstratedbythehuman
genomeProject.
MATCHING:PARTB_ANSWERS
A.Frameshiftmutation
B.Missensemutation
C.synonymouspolymorphism
D.pointmutations
E.Geneconversion
F.nonsynonymouspolymorphism
G.Nonsensemutation
H.Gainoffunctionmutations
I.Inactivatingmutations
J.Haploinsufficiency
D.Mutationsinvolvingsinglenucleotides
B.DNAsequencechangethatoccursinacodingregionandtherebyaltersanaminoacidsequence
3
C.DNAsequencevariationsthatdonotresultinaperceptiblephenotypeandconsistofsinglebase
pairsubstitutionsthatdonotaltertheproteincodingsequencebecauseofthedegeneratenatureofthe
geneticcode
4
A.Smallnucleotidedeletionsorinsertionsthatcauseashiftofthecodonreadingframe
5
F.SequencevariationsthataltermRNAstability,translation,oraminoacidsequence,butdonot
resultinaperceptiblephenotype.
6
G.Readingframealterationsthatresultinanabnormalproteinsegmentofvariablelengthbefore
terminationoftranslationoccursatastopcodon
7
E.nonreciprocalexchangeofhomologousgeneticinformation,usedtoexplainhowaninternal
portionofageneisreplacedbyahomologoussegmentcopiedfromanotheralleleorlocus.
8
J.Mutationinasinglealleleandinwhichonenormalalleleisnotcapableofmaintaininganormal
phenotype,seeninVonHippelLindausyndromeandotherdiseasesassociatedwithmutationsin
transcriptionfactors.
1. H.Mutationistypicallydominant,andresultsinphenotypicalterationswhenasinglealleleisaffected.
2. I.Mutationistypicallyrecessive,andtheaffectedindividualiseitherhomozygousorcompound
heterozygousforthediseasecausingmutations.