载脂蛋白A5基因变异与动脉粥样硬化性心血管疾病.pptVIP

A newly described member of the apolipoprotein gene family Discovered from comparative sequence analysis of the mammalian (human mouse) APOA1/C3/A4 gene cluster (Len A. Pennacchio; Edward M. Rubin. 2001) Gene ：4155bp, with 4 exans, 1107bp ORF Located at 30kb downstream of APOA1/C3/A4 on human chromosome 11q23 Expressed only in liver, secreted into blood stream Protein： 343 aa，MW 39 kDa, A very hydrophobic, highly α-helical protein Plasma level 24-406ug/L，presented in VLDL, HDL and CM human and mouse APOA5 display 71% amino acid identity and 78% similarity 66% decrease in TG ApoA5 mRNA APOA5 contains a PPRE that confers responsiveness to PPAR The APOA5 LD and haplotype structure has been investigatedin three ethnic groups(Chinese, Malays and Indians) Compared with Caucasian populations these Asian groups have higher frequencies of each of the minor alleles at 1131T C, 3A G, IVS3+476G A, 1259T C. Chinese and Malays have higher frequencies of the minor alleles than Indians. Conversely, the frequencies of the minor allele at the 56C G are significantly lower among these Asian groups than in Caucasians (less than 1% in Chinese versus 6% in Caucasians). Regarding the LD in the entire gene cluster, the information in Asians is scarce, needs more in depth examination. In this regard, the International HapMap Consortium began in late 2002 the HapMap project with the ultimate goal of identifying htSNPs that can tag the entire human genome. (/abouthapmap.htmlweb site) The initial project is to genotype at least one million SNPs among 270 subjects from three major ethnic groups: Caucasians, Asians and Africans. Thank you 在同一基因座或区域的多态性位点往往存在连锁不平衡（linkage disequilibrium，LD），常可作为遗传标记分析与某种疾病的相关性；结合候选基因或区域内的多个变异（单倍型），可作为对于特定疾病危险性的一个功能单位，而且这种功能单位可在遗传漂变、选择或因缺乏重组而得以保留。单倍型由于减少了独立变量，在相关性研究中可增加统计学效率；若能寻找出常见单倍型中的标签多态性（haplot