DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene
DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene
复制标题
DOI：
10.1038/907
复制
发表时间：
1998-07-01
期刊：
影响因子：
30.8
通讯作者：
Sing, CF
中科院分区：
文献类型：
--
作者：
Nickerson, DA;Taylor, SL;Sing, CF
脂蛋白脂肪酶在脂质代谢中起核心作用，编码该酶的基因（LPL）是心血管疾病的一个候选易感基因。在此我们报告了来自三个可能具有不同历史从而影响序列变异结构的群体的71个个体（142条染色体）的LPL基因一部分的完整序列。在这9.7kb中，有88个位点在这三个群体的个体之间存在差异。其中，79个是单核苷酸替换，9个位点涉及插入 - 缺失变异。该区域的平均核苷酸多样性为0.2%（平均每500bp有1个变异位点）。在这些位点中的34个位点上，变异仅在其中一个群体中发现，这反映了不同的群体和突变历史。如果LPL是一个典型的人类基因，那么在内含子以及外显子中存在的序列变异模式，即使是对于这里所考虑的少量样本，也将对识别影响广大人群疾病风险变异的位点或位点组合提出挑战。
Lipoprotein lipase plays a central role in lipid metabolism and the gene that encodes this enzyme (LPL) is a candidate susceptibility gene for cardiovascular disease. Here we report the complete sequence of a fraction of the LPL gene for 71 individuals (142 chromosomes) from three populations that may have different histories affecting the organization of the sequence variation. Eighty-eight sites in this 9.7 kb vary among individuals from these three populations. Of these, 79 were single nucleotide substitutions and 9 sites involved insertion-deletion variations. The average nucleotide diversity across the region was 0.2% (or on average 1 variable site every 500 bp). At 34 of these sites, the variation was found in only one of the populations, reflecting the differing population and mutational histories. If LPL is a typical human gene, the pattern of sequence variation that exists in introns as well as exons, even for the small number of samples considered here, will present challenges for the identification of sites, or combinations of sites, that influence Variation in risk of disease in the population at large.