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首页> 外文学位 >Genetic variation and linkage disequilibrium in the human alcohol dehydrogenase genes: Implications of the evolutionary history of a gene family in humans.
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Genetic variation and linkage disequilibrium in the human alcohol dehydrogenase genes: Implications of the evolutionary history of a gene family in humans.

机译：人类酒精脱氢酶基因的遗传变异和连锁不平衡：人类基因家族进化史的意义。

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摘要

The nature of genetic variation and the nature and extent of linkage disequilibrium in the alcohol dehydrogenase (ADH) genes in >30 populations from around the world was studied. These analyses were undertaken to determine the implications of the population genetics of the ADH genes in studies of human evolution and the epidemiology of alcoholism.; We found that genetic variation in the ADH genes is generally similar within large geographic regions with a few exceptions such as in populations that have undergone strong founder effects. Between geographic regions, there are differences in the nature of variation, especially between the east Asian samples we studied and all other geographic regions. In contrast to the nature of variation, linkage disequilibrium is strong in all populations across the Class I ADH genes. While there is no clear overall pattern, pairwise linkage disequilibrium between some Class I ADH SNPs and the ADH4 and ADH7 SNPs is weak but significant in some populations. Tests for evidence of linkage disequilibrium across the segments between the Class I ADH SNPs taken as a whole and the ADH4 and ADH7 SNPs are insignificant except for a few populations.; Using a haplotype-based method of testing for independent functional effects of polymorphic sites under conditions of linkage disequilibrium for a subset of the SNPs, we found that previous interpretations of association studies claiming that the ADH1B Arg47His and ADH1C Ile349Val polymorphisms have an independent effect need to be re-examined. Based on the impact of linkage disequilibrium on the interpretation of association studies and the extent of linkage disequilibrium in some populations, it seems prudent for future studies of the role of the ADHs in the protection against alcoholism to test and account for linkage disequilibrium within the ADH gene family as a whole on a sample-by-sample and site-by-site basis. Indeed, we have found a new SNP 6bp downstream from the frequently studied ADH1C Ile349Val site in ADH1C which results in a Pro-Thr amino acid substitution and is almost exclusive to Amerindians. This site may be relevant to protection against alcoholism in Amerindian populations but has been previously unexamined.
机译：研究了全世界30多个人群中酒精脱氢酶（ADH）基因的遗传变异性质以及连锁不平衡的性质和程度。进行了这些分析，以确定ADH基因的群体遗传学在人类进化和酒精中毒流行病学研究中的意义。我们发现，在较大的地理区域内，ADH基因的遗传变异通常相似，只有少数例外，例如在经历了强大的奠基者效应的人群中。在地理区域之间，变异的性质存在差异，尤其是在我们研究的东亚样本与所有其他地理区域之间。与变异的本质相反，在I类ADH基因的所有种群中，连锁不平衡很强。尽管没有明确的总体模式，但在某些人群中，某些I类ADH SNP与ADH4和ADH7 SNP之间的成对连锁不平衡很弱，但很明显。除少数人群外，在整个I类ADH SNP与ADH4和ADH7 SNP之间的片段之间连锁不平衡的证据的测试均不重要。使用基于单倍型的方法测试一个SNP子集在连锁不平衡条件下多态性位点的独立功能作用，我们发现先前的关联研究解释声称ADH1B Arg47His和ADH1C Ile349Val多态性对重新检查。基于连锁不平衡对关联研究的解释的影响以及某些人群中连锁不平衡的程度，对于未来研究ADH在防止酒精中毒中的作用的研究似乎是谨慎的做法，以测试和解释ADH中的连锁不平衡。整个基因家族在逐个样本和逐个站点的基础上进行。实际上，我们在ADH1C中经常研究的ADH1C Ile349Val位点下游发现了一个6bp的新SNP，导致Pro-Thr氨基酸取代，几乎是美洲印第安人所独有的。此站点可能与防止美洲印第安人人群中的酗酒有关，但以前未进行过检查。

著录项

  • 作者

    Osier, Michael Vernon.;

  • 作者单位

    Yale University.;

  • 授予单位 Yale University.;
  • 学科 Biology Genetics.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 207 p.
  • 总页数 207
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 遗传学;
  • 关键词

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