遺傳疾病的分類第1頁，共11頁，2023年，2月20日，星期日Fig.13.3?ScionPublishingLtdEtiologyofdiseases.Foranyconditiontheoverallbalanceofgeneticandenvironmentaldeterminantscanberepresentedbyapointsomewherewithinthetriangle.第2頁，共11頁，2023年，2月20日，星期日ClassificationofgeneticdisordersMultifactorial

Singlegene

ChromosomalMitochondrial

Somaticmutations(cancer)

Male+environment第3頁，共11頁，2023年，2月20日，星期日Fig.1.15?ScionPublishingLtdContinuumofpenetrance.

Thereisacontinuumofpenetrancefromfullypenetrantconditions,whereothergenesandenvironmentalfactorshavenoeffect,throughtolow-penetrancegenesthatsimplyplayasmallpart,alongwithothergeneticandenvironmentalfactors,indeterminingaperson’ssusceptibilitytoadisease.Multiplesclerosisisusedasanexampleofamultifactorialconditionwheregeneticfactorsplayamajorpartindeterminingsusceptibility,butcurrentresearchsuggeststhateachindividualfactorhasaverylowpenetrance.第4頁，共11頁，2023年，2月20日，星期日GeneticfactorsMaleMutationsinsingle

genes(oftencausinglossoffunction)VariantsingenescausingalterationoffunctionChromosomalimbalancecausesalterationingenedosage第5頁，共11頁，2023年，2月20日，星期日ClassificationofgeneticdisordersMaleMutationsinsinglegenesVariantsingenesChromosomalimbalanceSingleGeneDisordersMultifactorialdiseasesChromosomedisorders+environment第6頁，共11頁，2023年，2月20日，星期日RecessiveHomozygoteswithtwocopies

ofthealteredgeneareaffectedDominantHeterozygoteswithonecopy

ofthealteredgeneareaffectedX-linkedrecessiveMaleswithonecopy

ofthealteredgeneontheX-chromosomeareaffectedMale第7頁，共11頁，2023年，2月20日，星期日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頁，共11頁，2023年，2月20日，星期日

GENETIC

ENVIRONMENTAL

DuchennemusculardystrophyHaemophiliaOsteogenesisimperfectaClubfoot

Pyloricstenosis

DislocationofhipPepticulcer

DiabetesTuberculosisPhenylketonuria

GalactosaemiaSpinabifida

Ischaemicheartdisease

AnkylosingspondylitisScurvyThecontributionsofgeneticandenvironmentalfactorstohumandiseasesRare

Geneticssimple

Unifactorial

HighrecurrencerateCommon

Geneticscomplex

Multifactorial

Lowrecurrencerate第9頁，共11頁，2023年，2月20日，星期日Multifactorial

“Environmental”influencesactonageneticpredisposition

Oneorgansystemaffected

Singlegene

Dominant/recessivepedigreepatterns

Structuralproteins,enzymes,receptors,transcriptionfactors

Chromosomal

Multipleorgansystemsaffected

Inheritedordenovo

Environmental

Drugs,infections第10頁，共11頁，2023年，2月20日，星期日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:7II