武汉大学：《遗传学》课程教学课件（英文讲稿）Chapter 10A Analyzing genomic variation-5E1

Chapter10Analyzing genomic variation11-1

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Sectionsto study10.1 Variation among individual genomes10.2 Four classes of DNA polymorphisms10.4 Positional cloning -Use of polymorphic DNA markers toclonedisease-causinggenes11-2

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-2 Sections to study Sections to study 10.1 Variation among individual genomes 10.1 Variation among individual genomes 10.2 Four classes of DNA polymorphisms 10.2 Four classes of DNA polymorphisms 10.4 Positional cloning 10.4 Positional cloning – Use of polymorphic DNA markers to Use of polymorphic DNA markers to clone disease clone disease-causing genes causing genes

10.1 Variation amongindividualgenomesChromosomeomatid ChromatidhatureTlomnreCentromereolomareCellNAdoubinhalMDA0O2001AmeficanAaaocisfionlortheAdvan

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James WatsonJ.CraigVenter(Genome published2007-02)(Gen0mepublished2007-09)116.800K117M116.750K116.850K116.900K116.950K117.050KWatsonVenterAllSNPs干Genes十ASZ1WNT2CFTRSNP variation in a region onchromosome7Fig.10.511-4

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-4 J. Craig Venter (Genome published 2007-09) James Watson (Genome published 2007-02) Fig. 10.5 SNP variation in a region on chromosome 7

JamesWatsonJ.CraigVenterYH(a)(b)YH978.3702443435,493509,17591710801,151,0592622924,3331,096,87323742641564,716976VenterWatsonVenterWatsonSingle nucleotide substitutionsAmino acid-changing substitutionsFigure11.211-5

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Why the amino acid-changing differences are not abundant?Less than 2% of the humangenome codes for genes.Even when mutations occur, many mutations of codons aresilent (don'tchange the amino acid).If a particular mutation is not silent and has deleteriouseffects,natural selection could often lead to its disappearancefromthehumanpopulation11-6

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-6  Less than 2% of the human genome codes for genes. Less than 2% of the human genome codes for genes.  Even when mutations occur, many mutations of Even when mutations occur, many mutations of codons are silent (don silent (don’t change the amino acid). t change the amino acid).  If a particular mutation is not silent and has deleterious If a particular mutation is not silent and has deleterious effects, natural selection could often lead to its disappearance effects, natural selection could often lead to its disappearance from the human population. from the human population. Why the amino acid-changing differences are not abundant?

1in1000 bp differencein anytwo randomly chosenhumans.3million differences betweenany two randomly chosenindividuals. (human haploidgenomeis3×109bp)Most differences are in non-coding, nonregulatoryregions.11-7

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-7  1 in 1000 1 in 1000 bp difference in any difference in any two randomly chosen two randomly chosen humans. humans.  3 million differences between 3 million differences between any two randomly chosen any two randomly chosen individuals. (human haploid individuals. (human haploid genome is 3 genome is 3  109 bp)  Most differences are in non Most differences are in non￾coding, coding, nonregulatory nonregulatory regions. regions

Extension to Mendelian definition of locus and allelein the post-genome eraModern geneticsMendelian geneticsLocusA geneA designated location anywhereona chromosomeAlternativeforms ofOneoftwo ormorealternativeDNAAllelesequencesfoundata locus-eitheragenecoding ornoncoding11-8

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-8 Extension to Mendelian definition of locus and allele in the post-genome era Mendelian genetics Modern genetics Locus A gene A designated location anywhere A designated location anywhere on a chromosome on a chromosome Allele One of two or more alternative DNA One of two or more alternative DNA sequences found at a locus sequences found at a locus – either coding or coding or noncoding noncoding Alternative forms of a gene

(DNA)polymorphism-agene ornoncodingregion thathastwoormorealleles.Polymorphic-a locus with two or more alleles in a population.DNA marker-a polymorphic locus useful for mapping studies.disease diagnosis and others.Anonymous locus-a locus on the chromosome without knownfunction.11-9

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 11-9  (DNA) polymorphism (DNA) polymorphism – a gene or a gene or noncoding noncoding region that has region that has two or more alleles. two or more alleles.  Polymorphic Polymorphic – a locus with two or more alleles in a population. a locus with two or more alleles in a population.  DNA marker DNA marker – a polymorphic locus useful for mapping studies, a polymorphic locus useful for mapping studies, disease diagnosis and others. disease diagnosis and others.  Anonymous locus Anonymous locus – a locus on the chromosome without known a locus on the chromosome without known function. function

10.2FourclassesofDNApolymorphismsTABLE10.1CategoriesofGeneticVariantsTheright column shows how frequently on averageyou would findapolymorphism of theindicated class when comparinganytwohaploidhumangenomes.Frequencysize(1 per....SNP1 kb1bpSinglenucleotidepolymorphism10kbDIP orIndel1-100bpInsertion/deletion1-10bp30kbSSRorMicrosatelliteSimple sequence repeatrepeat unitCNV3Mb10bp-1MbCopynumbervariant11-10

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