单核苷酸多态性snp-汕头大学医学院医学细胞生物学精品课程.ppt

Gene Variationssingle nucleotides polymorphismcopy number variation 刘戈飞 汕头大学医学院遗传学与细胞生物学教研室 gfliu@ 075488900497Genetic Markers Morphological markers Cytological markers Biochemical and physiological markers Molecular markers SNP Effects SNPs in genes In coding regions (possible protein structure changes) ? Synonymous substitutions (同义) ? Missense substitutions (错义) ? Nonsense substitutions (终止) In coding and non-coding regions ? Change of gene expression (by diverse binding various factors) Yield Timing Alternative splicing SNPs in regulatory regions Change of gene expression SNPs in non-regulatory intergenic regions Can be used as genetic markers 人类的所有群体中大约存在一千万个SNP位点，其中稀有的SNP位点的频率至少有1%。 相邻SNPs的等位位点倾向于以一个整体遗传给后代。位于染色体上某一区域的一组相关联的SNP等位位点被称作单体型(haplotype)。 大多数染色体区域只有少数几个常见的单体型(每个具有至少5%的频率)，它们代表了一个群体中人与人之间的大部分多态性。一个染色体区域可以有很多SNP位点，但是只用少数几个标签SNPs，就能够提供该区域内大多数的遗传多态模式。 HapMap的构建分为三个步骤：a在多个个体的DNA样品中鉴定单核苷酸多态性SNPs；b将群体中频率大于1%的那些共同遗传的相邻SNPs组合成单体型；c在单体型中找出用于识别这些单体型的标签SNPs。通过对图中的三个标签SNPs进行基因分型，研究者可以确定每个个体拥有图示的四个单体型中的哪一个。 单体型的起源 How to discover SNPs SNP检定— Genotyping 目标：灵敏、准确、简单、高通量、低成本 SNP screening of certain genes SNP raise the resolution of genetic analysis Pharmacogenomics Personalize medicine Forty-three authors used the DNA from 270 individuals from the 4 HapMap populations. Overall, the authors found 1,447 discrete, heterogeneously distributed, copy number variable regions (CNVRs), which cover 12% of the human genome. They found that 24% of CNVRs are associated with segmental duplications. CNVRs contain different classes of functional elements. many CNVs preferentially lie outside genes. genes that are involved in cell-adhesion functions, sensory perception of smell and response to chemical stimuli are enriched within CNVs. Conversely, cell signalling and proliferation, as well as kinase-and phosphorylationrelated categories were underrepresented among CNVs. Interestingly, ultraconserved elements are strongly excluded