1MedicalGenetics2GeneticsinMedicine7thed.,2007

李璞主編陳竺主編4Introduction5Genetics（遺傳學）HeredityandVariation—alllivingorganismshereditary

factorTheoryof

Gene6HumanGenetics

7MedicalGeneticsMedicalGenetics

istheapplicationofgeneticstomedicalpractice.

Diseases—Inheritance

ClinicalGeneticsDiagnosisPreventionCounselingTreatment8WaterlandRA,JirtleRA.Transposableelements:targetsforearlynutritionaleffectsonepigeneticgeneregulation.Mol.Cell.Biol.,2003,23:5293-5300Epigenetics9EpigeneticsRegulationofgeneexpressionwithoutchangesinDNAsequences

Epigeneticinheritance（表觀遺傳）Epigenetics（表觀遺傳學）10GeneticBasisofHealthandDiseasesGeneticstructure

Environmentalconditions11AnydiseaseistheresultofthecombinedactionofgenesandenvironmentGenesandEnvironment12GeneticdisordersThediseasesarecausedbygeneticfactor.

genesorchromosomes13遺傳病的特點（一）遺傳病的先天性（二）遺傳病的家族性（三）垂直傳遞（四）遺傳病的“終生性”（五）遺傳病的“罕見性”14遺傳病的特點（一）遺傳病的先天性（二）遺傳病的家族性（三）垂直傳遞（四）遺傳病的“終生性”（五）遺傳病的“罕見性”15遺傳病:先天性

家族性16遺傳病的特點（一）遺傳病的先天性（二）遺傳病的家族性（三）垂直傳遞（四）遺傳病的“終生性”（五）遺傳病的“罕見性”17遺傳病的特點（一）遺傳病的先天性（二）遺傳病的家族性（三）垂直傳遞（四）遺傳病的“終生性”（五）遺傳病的“罕見性”18Inthecrowd

monogenicdisease3%~5%

polygenicdisease15%~20%

chromosomedisease1%

TheHazardofGeneticDiseasespontaneousabortion(自發流產）

50%relatetochromosomalaberration19約1.3%有嚴重的出生缺陷或先天畸形我國大約有1500萬新生兒70~80%涉及遺傳因素：13~15萬50%由染色體畸變引起：112萬自然流產約占15%已存活的兒童，住院就診的約有1/4~1/3患與遺傳有關的疾病TheHazardofGeneticDisease20

據估計，人群中平均每個人都攜帶5～6個隱性有害基因。他們沒有患病，稱為致病基因的攜帶者(carrier)，可將有害基因傳遞給后代，形成遺傳負荷(geneticload)。TheHazardofGeneticDisease21

體細胞遺傳病中的惡性腫瘤構成我國不同地區人群死亡原因的第一或第二位。

我國人群中智力低下的發生率約為2.2％，其中1/3以上有多基因、單基因或染色體改變的基礎。TheHazardofGeneticDisease22ClassificationofGeneticDiseasesSingle-genedisorders(單基因病）Polygenicdisorders（多基因病）Chromosomaldisorders（染色體病）Geneticdiseasesofmitochondria(Mt)（線粒體遺傳病）SomaticcellGeneticdisorders（體細胞遺傳病）23Single-geneDisorders

Single-gene(ormonogenic)disordersresultfromthemutationofgene.ADARXDXRY24Huntingtonchorea(AD)25PKU(AR)苯丙氨酸羥化酶（PAH）基因突變基因定位于12q24.1，85kb,13外顯子26DMD(XR)

假肥大型肌營養不良Xp21.2-p21.3,75exon,2300kbOMIMStatisticsforFebruary7,2012

Autosomal19775X-linked1170Y-linked59Mitochondrial6521069/entrez/Omim/mimstats.html28OMIM29PolygenicDisordersGeneticbackgroundEnvironmentalfactors

CongenitaldefectsCommondiseases.2930Schizophrenia31

cleftlip±cleftpalate32Chromosomaldisorders

Diseasescausedbychromosomalabnormalities

growthretardationmentalretardationsomaticabnormalities3334

GeneticDiseasesofMitochondria

MutationofMtgenesMaternalheredity35Leberhereditaryopticneuropathy36SomaticCellGeneticDisorders

Resultfromthealteredgeneticmaterialsinsomaticcells.

Tumor&congenitalmalformation37RetinoblastomaRB基因：13q14.1,27exon38Master:

DefinitionofgeneticdisordersClassificationofgeneticdisorders39TheHumanGenomeand

theChromosomalBasis

ofHeredity40DNA—Chromosome41Mitosis42homologouschromosomeMeiosis43ProphaseILeptotene(細線期):ChromosomesbegintocondenseZygotene(偶線期):Homologouschromosomesbegintopair;synapsiscomplexesform;bivalent（二價體）Pachytene(粗線期):Crossingover;tetrad（四分體）Diplotene(雙線期):Homologouschromosomesseparate;remainattached-chiasmaDiakinesis(終變期):Separationofhomologouschromosomes

細線期偶線期粗線期雙線期終變期45homologouschromosomes（同源染色體）synapsis(聯會):homologouschromosomespaircloselyalongtheirentirelengthatzygotenecrossingover(交換):takesplaceatpachytene46metacentric（中著絲粒）submetacentric（亞中著絲粒）acrocentric（近端著絲粒）

Classification

ofHumanChromosomes人類47Karyotype（核型）Thekaryotypeisaphotographofallofthechromosomesofanindividualcell;thetermcoversthenumber,relativesizesandstructureofthechromosomes.48Master:HumanChromosomesKaryotypeCellcycleMitosisandmeiosisHumangenomeUniquesequenceRepetitivesequenceHighlyrepetitivesequenceIntermediaterepetitivesequenceMultigenefamily50GeneOrganizationandStructure

Gene(基因)

Astructuralunitofinheritance.AsequenceofDNA(orRNA)thatisrequiredforproductionofafunctionalproduct.51GeneOrganizationandStructure

Splitgene(斷裂基因)

Inmosteukaryoticgenome,genescontainingcodingregions(exons)thatareinterruptedbynoncodingregions(introns).52ExonIntronTATAboxCAATboxGCboxEnhancerRegulatorSequence