Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.
Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.
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人类脂蛋白脂肪酶基因内的分支结构及其对表型关联研究的影响。
DOI：
10.1093/genetics/156.3.1259
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发表时间：
2000
期刊：
影响因子：
3.3
通讯作者：
Sing,CF
中科院分区：
文献类型：
--
作者：
Templeton,AR;Weiss,KM;Nickerson,DA;Boerwinkle,E;Sing,CF
人类脂蛋白脂酶（LPL）基因的9.7 kb基因组DNA序列的单倍型变异在三个人群中进行了评分：来自密西西比杰克逊的非洲裔美国人（24人），来自芬兰北卡累利阿的芬兰人（24人）和来自明尼苏达州罗切斯特的非西班牙裔白人（23人）。早期的分析表明，重组是常见的，但集中在一个热点，并在多个位点的复发突变可能已经发生。我们发现，许多进化结构存在于重组热点两侧的单倍型变异中。剥离显着的重组事件从树估计下的零假设没有重组，我们也揭示了一些分支结构不重组期间合并的变化。另外的分支结构估计已经出现重组后。在去除检测到的重组/基因转换事件的影响后，位点处的许多明显的多重突变事件仍然存在。这些明显的多重事件主要发现在以前的研究中确定为高度可变的位点，加强了它们是真正的多重事件的结论。该分析描绘了许多重组和突变事件之间相互作用的复杂性，这些事件需要解释该基因中单倍型多样性的模式。在这个区域的分支结构被用来确定四到六个单核苷酸多态性（SNPs），将提供不平衡的覆盖范围在这个地区的大部分。这些位点可用于鉴定与该基因中可变位点的表型关联。进化的考虑也意味着3′区的SNPs在大多数人群中应该具有普遍的效用，但5′区的SNPs可能更具群体特异性。随机选择SNP通常不会提供测序区域的足够的不平衡覆盖。
Haplotype variation in 9.7 kb of genomic DNA sequence from the humanlipoprotein lipase(LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3′ region should have general utility in most human populations, but the 5′ SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region.