[医学保健]Gene Variations single nucleotides polymorphism.pptVIP

Gene Variationssingle nucleotides polymorphismcopy number variation 汕头大学医学院遗传学与细胞生物学教研室 Genetic 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 from these regions. CNV has effects