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MonogenicDiseaseTerminologyPedigreesymbol&PedigreeanalysisPedigreecharacteristicsTypesofADInfluentialfactorEstimateofrecurrenceriskEmphasisDominant(A)&

Recessive(a)Locus&

Allele(multiplealleles)TerminologyHomozygote:AA

oraaHeterozygote:AaGenotype&PhenotypeThepedigreeisavisualtoolfordocumentingbiologicalrelationshipsinfamiliesandthepresenceoftraitsordiseases.1.Pedigree1.PedigreeProband(indexcase)Probandisthefirstaffectedfamilymemberwhoseeksmedicalattentionforageneticdisorder.1.Pedigree1.1.PedigreeSymbolIII121231.Pedigree1.1.PedigreeSymbolInformationoffamilymembersmorethanthreegenerationsInformationverifiedbygeneticconsultantInvestigatingthedeathcause,deathage,consanguineousmarriage,fetaldeath,abortion,neonataldeath1.Pedigree1.2.PedigreeAnalysisADinheritancearethoseinwhichasinglecopyofamutantgeneon

autosomeisenoughforthetraittobeexpressedorshown.2.AutosomalDominant(AD)Thephenotypeoftheheterozygote(Aa)willbeindistinguishablefromthephenotypeofthehomozygous(AA)dominant.2.AutosomalDominant(AD)2.1.CompleteDominance

Brachydactyly,typeA1(MIM112500)2.AutosomalDominant(AD)2.1.CompleteDominance

（引自高波等，2001）Brachydactyly,typeA1(MIM112500)2.AutosomalDominant(AD)2.1.CompleteDominance

PedigreeofAD2.AutosomalDominant(AD)2.1.CompleteDominance

×PedigreecharacteristicsEachaffectedindividualhasoneaffectedparent50%ofsibsandoffspringareaffectedMalesandfemalesareaffectedwithequalprobabilityPassedinaverticalfashion2.AutosomalDominant(AD)2.1.CompleteDominance

Thephenotypeoftheheterozygote(Aa)willbeintermediatebetweenthephenotypesofthetwohomozygotes(AAoraa).2.AutosomalDominant(AD)2.2.IncompleteDominance

Achondroplasia

(MIM100800)2.AutosomalDominant(AD)2.2.IncompleteDominance

（引自WolfWikisNorthCarolinaStateUniversity）12IIIIII1231Achondroplasia

(MIM100800)2.AutosomalDominant(AD)2.2.IncompleteDominance

（引自WolfWikisNorthCarolinaStateUniversity）Bothalleleswillbecompletelyexpressedintheheterozygote,andtheindividualhasadifferentphenotypethanthatofeitherhomozygote.MNbloodgroup(MIM111300)ABObloodgroup(MIM110300)2.AutosomalDominant(AD)2.3.Codominance

ABObloodgroup(MIM110300)GenotypePhenotype(bloodgroup)AA,AOABB,BOBABABOOO2.AutosomalDominant(AD)2.3.Codominance

ABObloodgroup(MIM110300)2.AutosomalDominant(AD)2.3.Codominance

FUT1(19q13.33)

ABO(9q34)FUT2(19q13.33)Sometimetheheterozygote(Aa

)willnotshowthephenotypesofdominantallele,orshowdifferentclinicalsymptomsofit.2.AutosomalDominant(AD)2.4.Irregular

Dominance

PenetrancePenetranceingeneticsistheproportionofindividualscarryingaparticularvariationofagene(alleleorgenotype)thatalsoexpressanassociatedtrait(phenotype).2.AutosomalDominant(AD)2.4.Irregular

Dominance

Polydactyly,postaxial,typeA1(MIM174200)2.AutosomalDominant(AD)2.4.Irregular

Dominance

123123412312IIIIIIIVPolydactyly,postaxial,typeA1(MIM174200)2.AutosomalDominant(AD)2.4.Irregular

Dominance

CompletepenetranceIncompletepenetranceFormefrusteSkippedgenerationPenetrance2.AutosomalDominant(AD)2.4.Irregular

Dominance

ExpressivityExpressivityisatermusedingeneticstorefertovariationsinaphenotypeamongindividualscarryingaparticulargenotype.2.AutosomalDominant(AD)2.4.Irregular

Dominance

MultiplefractureOsteogenesisimperfecta,typeⅠ(MIM166200)2.AutosomalDominant(AD)2.4.Irregular

Dominance

BluescleraDeafness2.AutosomalDominant(AD)2.4.Irregular

Dominance

Osteogenesisimperfecta,typeⅠ(MIM166200)MultiplefractureBluescleraDeafness1

2

31

2

31

2IIIIIIIV1

2

3Marfansyndrome(MIM154700)2.AutosomalDominant(AD)2.4.Irregular

Dominance

Marfansyndrome(MIM154700)2.AutosomalDominant(AD)2.4.Irregular

Dominance

Marfansyndrome(MIM154700)2.AutosomalDominant(AD)2.4.Irregular

Dominance

Marfansyndrome(MIM154700)2.AutosomalDominant(AD)2.4.Irregular

Dominance

Notallgeneticdisordersarecongenital,someareexpressedatacharacteristicageandothersatvariableages.2.AutosomalDominant(AD)2.5.DelayedDominance

2.AutosomalDominant(AD)2.5.DelayedDominance

Huntingtondisease(MIM143100)12345IIIIII121234042452132Exon:(CAG)nn=9~34,average20n=37~100,average46Huntingtin(IT15):4p16.3DynamicmutationHuntingtondisease(MIM143100)2.AutosomalDominant(AD)2.5.DelayedDominance

Huntingtondisease(MIM143100)2.AutosomalDominant(AD)2.5.DelayedDominance

(CAG)n1003840262711142ARinheritancearecharacterizedonlyinindividualshomozygousforthemutantgeneonautosome.3.AutosomalRecessive(AR)Carrier(Aa

)Anindividualthatcarriesonegeneforaparticularrecessivetrait.Acarrierdoesnotexpressthetraitbut,whenmatedwithanothercarrier,canproduceoffspringthatdo.3.AutosomalRecessive(AR)PedigreeofAR3.AutosomalRecessive(AR)××PedigreeofAR3.AutosomalRecessive(AR)PedigreecharacteristicsBothparentsarecarriers1/4ofsibsareaffected.Malesandfemalesareaffectedwithequalprobability2/3ofunaffectedsibsarecarriersThediseasesaresporadicTheriskofoffspringishigherinconsanguineousmarriage3.AutosomalRecessive(AR)ARdiseasesSicklecelldisease(MIM603903)Sickle-celldisease(SCD),orsickle-cellanaemia(SCA),isanARgeneticblooddisorderwithco-dominance,characterizedbyredbloodcellsthatassumeanabnormal,rigid,sickleshape.3.AutosomalRecessive(AR)ARdiseasesSicklecelldisease(MIM603903)3.AutosomalRecessive(AR)ValHisLeuProGluGluLysThrHBAValHisLeuProGluLysValThrHBSGAGGTGARdiseasesSicklecelldisease(MIM603903)3.AutosomalRecessive(AR)O2HbAHbSO2ARdiseasesSicklecelldisease(MIM603903)3.AutosomalRecessive(AR)ARdiseasesSicklecelldisease(MIM603903)3.AutosomalRecessive(AR)ARdiseasesSicklecelldisease(MIM603903)3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)Phenylketonuria(PKU)isarare,inherited,metabolicdisorderresultingfromadeficiencyofphenylalaninehydroxylase(PAH).3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)1in13333births3.AutosomalRecessive(AR)Metabolismofphenylalanine(Phe)PheProteinPAHTyrProteinMelaninAlkaptonAcetoaceticacidCO2+H2O×PhenyllacticacidBenzophenonePhenylypruvicacidPhenylaceticacid“Mousy”smellinthesweatandurineLightercoloredskin,hair,andeyesMentalretardation3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)Guthrietest24hoursafterbirth,usuallydoneatage7to10daysAurinePKUtestisdoneonababywhoisolderthan6weeks3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)Guthrietest3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)Guthrietest3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)GuthrietestAnormalbloodphenylalaninelevelisabout1mg/dlIncasesofPKU,levelsmayrangefrom6~80mg/dl,butareusuallygreaterthan30mg/dl3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)Astrictlycontrolledphenylalaninefreedietuptotheageofabout14yearsoldPhenylalanineisitselfanessentialaminoacidsmalldosesmustbesupplied3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)ThegoalofPKUtreatmentistomaintainthebloodlevelsofpheylalaninebetween2~10mg/dl3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)WomenwithPKUwhowishtobecomepregnantMentalretardation92%Microcephaly73%Congenitalheartdefects12%3.AutosomalRecessive(AR)ARdiseasesPhenylketonuria(MIM261600)WomenwithPKUwhowishtobecomepregnantmustalsoeatthespecialdiet.ARdiseasesAlbinism,oculocutaneous,typeIAOCA1A(MIM203100)isageneticallyheterogeneouscongenitaldisordercausedbymutationsinthetyrosinasegene.3.AutosomalRecessive(AR)ARdiseasesAlbinism,oculocutaneous,typeIA1in20000~10000births3.AutosomalRecessive(AR)TyrDopaMelaninTyrosinaseTyrosinase×3.AutosomalRecessive(AR)ARdiseasesAlbinism,oculocutaneous,typeIA×Characterizedbydecreasedorabsentpigmentationinthehair,skin,andeyes.3.AutosomalRecessive(AR)ARdiseasesAlbinism,oculocutaneous,typeIA3.AutosomalRecessive(AR)ARdiseasesAlbinism,oculocutaneous,typeIA3.AutosomalRecessive(AR)ARdiseasesAlbinism,oculocutaneous,typeIATwoquestionsSmallfamilyConsanguineousmarriage3.AutosomalRecessive(AR)TwoquestionsSmallfamilyCompleteascertainmentIncompleteascertainmentTruncateascertainment3.AutosomalRecessive(AR)TwoquestionsSmallfamilyAcoupleofcarrierOnechildTwochild3.AutosomalRecessive(AR)TwoquestionsConsanguineousmarriageConsanguinityAhereditaryor“blood”relationshipbetweenpersons,becauseofhavingacommonparentorancestor.3.AutosomalRecessive(AR)CoefficientofrelationshipProbabilitythatanytwoindividualsshareagivengeneatarandomlocusbydescendedfromacommonancestor.3.AutosomalRecessive(AR)TwoquestionsConsanguineousmarriageFirstdegreerelatives1/2Seconddegreerelatives1/4Thirddegreerelatives1/83.AutosomalRecessive(AR)CoefficientofrelationshipTwoquestionsConsanguineousmarriageCoefficientofrelationship

Type

DegreeofRelationshipProportionofGenesinCommonMZtwins-1Parents,offspring,full-sibs(includingdizygotictwins)1st1/2Grandparents,grandchildren,half-sibs,aunts/uncles,nieces/nephews,doublefirstcousins2nd1/4Firstcousins,half-nieces/nephews,half-aunts/uncles3rd1/8Halffirstcousins,firstcousinsonceremoved4th1/16Secondcousins5th1/32TwoquestionsConsanguineousmarriageThegenefrequencyofARis0.01thefrequencyofcarrieris0.02ThegenefrequencyofARis0.001thefrequencyofcarrieris0.0023.AutosomalRecessive(AR)ConclusionConsanguineousmarriage>RandommarriageTherarertheARis,thehighertheriskshouldbe3.AutosomalRecessive(AR)TwoquestionsConsanguineousmarriageHemizygoteHemizygotedescribesadiploidmalewhohasonlyonealleleontheX-chromosomeoroneX-chromosomeratherthantheusualtwoinadiploidfemale.4.X-linkedInheritanceCriss-crossinheritanceAmalecanonlyreceivesanalleleontheX-chromosomefromhismotherand,canonlytransmitsittohisdaughter.Hemizygote4.X-linkedInheritance4.X-linkedInheritance4.1.X-linkedDominant

(XD)XDinheritancearethoseinwhichasinglecopyofamutantgeneontheXchromosomeinamaleorfemaleisenoughforthetraittobeexpressedorshown.×PedigreeofXD4.X-linkedInheritance4.1.X-linkedDominant

(XD)×PedigreeofXD4.X-linkedInheritance4.1.X-linkedDominant

(XD)PedigreecharacteristicsTheratioofaffectedfemalestothemalesisapproximately2to1EachaffectedindividualhasoneaffectedparentAffectedmalehavenoaffectedsonsandnonormaldaughters;50%offspringofaffectedfemalehavechanceofbeingaffectedPassedinaverticalfashion4.X-linkedInheritance4.1.X-linkedDominant

(XD)VitaminDresistantrickets(MIM307800)4.X-linkedInheritance4.1.X-linkedDominant

(XD)4.X-linkedInheritance4.2.X-linkedRecessive

(XR)XRinheritancearecharacterizedonlyinfemalehomozygousforthemutantgeneontheXchromosome.×4.X-linkedInheritance4.2.X-linkedRecessive

(XR)PedigreeofXR×4.X-linkedInheritance4.2.X-linkedRecessive

(XR)PedigreeofXR×4.X-linkedInheritance4.2.X-linkedRecessive

(XR)PedigreeofXRPedigreecharacteristicsMoreaffectedmalesthanaffectedfemalesEachsonhas1/2chanceofbeingaffectedBecauseofcriss-crossinheritance,who(?)ofaffectedindividualhavechanceofbeingaffectedPassedwithfemalecarriers4.X-linkedInheritance4.2.X-linkedRecessive

(XR)MusculardystrophyDuchenne(DMD)MIM3102004.X-linkedInheritance4.2.X-linkedRecessive

(XR)GowersignMusculardystrophyDuchenne(DMD)MIM310200Becker(BMD)MIM3003764.X-linkedInheritance4.2.X-linkedRecessive

(XR)HemophiliaA(MIM306700)Chromosome:Xq28Gene:FⅧc

4.X-linkedInheritance4.2.X-linkedRecessive

(XR)HemophiliaA:“theRoyalDisease”43332KingGeorgeⅢPrinceAlbertQueenVictoriaElizabethⅡ

AlexisJuanCarlosAliceBeatriceAlfonsoRed-greencolorblindnessOpsingenes4.X-linkedInheritance4.2.X-linkedRecessive

(XR)Red-greenColorblindness（引自

Googleimages）Red-greenColorblindnessRed-greenColorblindness（引自JOSHUAKENNON,2012）Red-greenColorblindnessHolandricinheritanceInheritanceofgenesontheYchromosome.SinceonlymaleshaveaYchromosome,Y-linkedgenescanonlybetransmittedfromfathertoson.5.Y-linkedInheritanceHairyEars(MIM425500)Holandricinheritance5.Y-linkedInheritanceAsimilarphenotypebeingcausedbydifferenthereditarybasis.AllelicheterogeneityLocusheterogeneity6.InfluencingFactor6.1.GeneticHeterogeneityLocusheterogeneityAsimilarphenotypebeingcausedbydifferentgenes.6.InfluencingFactor6.1.GeneticHeterogeneityDeafnessAutosomaldominantAutosomalrecessiveX-linkedrecessiveMitochondrialLocusheterogeneity6.InfluencingFactor6.1.GeneticHeterogeneityLocusheterogeneityDeafness,AR(MIM220700)1in1000individualsworldwide68%ofcongenitaldeafnessisARHomozygosityatanyoneof35loci16%ofpopulationarecarriers6.InfluencingFactor6.1.GeneticHeterogeneityLocusheterogeneityDeafness,AR(MIM220700)6.InfluencingFactor6.1.GeneticHeterogeneityDoubleheterozygoteLocusheterogeneityDeafness,AR(MIM220700)6.InfluencingFactor6.1.GeneticHeterogeneityPleiotropydescribesthegeneticeffectofasinglegene

onmultiplephenotypictraits.6.InfluencingFactor6.2.PleiotropySecondaryeffectPrimaryeffectThegeneticphenomenoninvolvedinthecontrolofasmallproportionofgenesinthegenome,wheretheallelethatisexpressedisdeterminedsolelyonwhichparentcontributesit.6.Influenc

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