遗传疾病的分类

遗传疾病的分类第1页，课件共11页，创作于2023年2月Fig.13.3©ScionPublishingLtdEtiologyofdiseases.Foranyconditiontheoverallbalanceofgeneticandenvironmentaldeterminantscanberepresentedbyapointsomewherewithinthetriangle.第2页，课件共11页，创作于2023年2月ClassificationofgeneticdisordersMultifactorial

Singlegene

ChromosomalMitochondrial

Somaticmutations(cancer)

Male+environment第3页，课件共11页，创作于2023年2月Fig.1.15©ScionPublishingLtdContinuumofpenetrance.

Thereisacontinuumofpenetrancefromfullypenetrantconditions,whereothergenesandenvironmentalfactorshavenoeffect,throughtolow-penetrancegenesthatsimplyplayasmallpart,alongwithothergeneticandenvironmentalfactors,indeterminingaperson’ssusceptibilitytoadisease.Multiplesclerosisisusedasanexampleofamultifactorialconditionwheregeneticfactorsplayamajorpartindeterminingsusceptibility,butcurrentresearchsuggeststhateachindividualfactorhasaverylowpenetrance.第4页，课件共11页，创作于2023年2月GeneticfactorsMaleMutationsinsingle

genes(oftencausinglossoffunction)VariantsingenescausingalterationoffunctionChromosomalimbalancecausesalterationingenedosage第5页，课件共11页，创作于2023年2月ClassificationofgeneticdisordersMaleMutationsinsinglegenesVariantsingenesChromosomalimbalanceSingleGeneDisordersMultifactorialdiseasesChromosomedisorders+environment第6页，课件共11页，创作于2023年2月RecessiveHomozygoteswithtwocopies

ofthealteredgeneareaffectedDominantHeterozygoteswithonecopy

ofthealteredgeneareaffectedX-linkedrecessiveMaleswithonecopy

ofthealteredgeneontheX-chromosomeareaffectedMale第7页，课件共11页，创作于2023年2月GeneticdisordersMultifactorial(common)

-“Environmental”influencesactonageneticpredispositiontoproducealiabilitytoadisease. -Oneorgansystemaffected. -Personaffectedifliabilityaboveathreshold.

Singlegene(1%liveborn)

-

Dominant/recessivepedigreepatterns(Mendelianinheritance).

-Canaffectstructuralproteins,enzymes,receptors,transcriptionfactors.

Chromosomal(0.6%liveborn) -Thousandsofgenesmaybeinvolved.

-Multipleorgansystemsaffectedatmultiplestagesingestation.

-Usuallydenovo(trisomies,deletions,duplications)butcanbeinherited(translocations).第8页，课件共11页，创作于2023年2月

GENETIC

ENVIRONMENTAL

DuchennemusculardystrophyHaemophiliaOsteogenesisimperfectaClubfoot

Pyloricstenosis

DislocationofhipPepticulcer

DiabetesTuberculosisPhenylketonuria

GalactosaemiaSpinabifida

Ischaemicheartdisease

AnkylosingspondylitisScurvyThecontributionsofgeneticandenvironmentalfactorstohumandiseasesRare

Geneticssimple

Unifactorial

HighrecurrencerateCommon

Geneticscomplex

Multifactorial

Lowrecurrencerate第9页，课件共11页，创作于2023年2月Multifactorial

“Environmental”influencesactonageneticpredisposition

Oneorgansystemaffected

Singlegene

Dominant/recessivepedigreepatterns

Structuralproteins,enzymes,receptors,transcriptionfactors

Chromosomal

Multipleorgansystemsaffected

Inheritedordenovo

Environmental

Drugs,infections第10页，课件共11页，创作于2023年2月SinglegenedisordersHighriskstorelativesDominant/recessivepedigreepatternsSomeisolatedcasesduetonewdominantmutationsStructuralproteins,enzymes,receptors,transcriptionfactorsI:1AAI:2ABII:1AAII:2ABII:3BB?III:1BBTomI:2I:1I:3II:1II:2II:3II:4II:5II:6II:7II:8II:9II:10II:11II:12II:13II:14II:15III:1III:2III:3IV:1IV:2IV:3IV:4III:4III:5IV:5IV:6IV:7I