Skin pigmentation, biogeographical ancestry and admixture mapping
Skin pigmentation, biogeographical ancestry and admixture mapping
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DOI：
10.1007/s00439-002-0896-y
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发表时间：
2003-04-01
期刊：
影响因子：
5.3
通讯作者：
Kittles, RA
中科院分区：
文献类型：
--
作者：
Shriver, MD;Parra, EJ;Kittles, RA
遗传信息标记（AIMs）是指在群体间显示出频率差异较大的等位基因的遗传位点。AIM可用于在人群、亚组（例如病例和对照）和个体水平上估计地理学祖先。在亚组和个体水平上的遗传学估计可以直接指导关于在群体之间在质量上或频率上不同的表型的遗传学。这些估计可以提供一个令人信服的基础，使用混合物映射（AM）的方法来确定这些性状的基因。我们提出了一个小组的34个AIM的细节，并展示了如何进行这样的研究，通过使用皮肤色素沉着作为一个模型表型。我们对两个主要为非洲血统的人群样本（即来自华盛顿特区的非裔美国人和来自英国的非裔加勒比人样本）以及来自宾夕法尼亚州的欧裔美国人样本中的这些标记进行了基因分型。在两个非洲人口样本中，我们观察到个体祖先的估计值与通过反射仪测量的皮肤色素沉着之间存在显著相关性（非裔美国人样本的R-2 = 0.21，P < 0.0001，英国非裔加勒比人样本的R-2 = 0.16，P < 0.0001）。这些相关性证实了血统估计的有效性，也表明了与混合物有关的高水平的人口结构，这是这些人口的特征，可以通过使用其他测试来确定遗传结构。我们还应用了两种混合作图的方法来测试三个候选基因（TYR，OCA 2，MC 1 R）对色素沉着的影响。我们发现，TYR和OCA 2对西非和西欧父母群体之间的皮肤色素沉着差异有可测量的影响。这项工作表明，有可能根据DNA分析和合理数量的明确定义的遗传标记来估计一个人的个体祖先。血统估计在生物医学研究中的影响和应用进行了讨论。
Ancestry informative markers (AIMs) are genetic loci showing alleles with large frequency differences between populations. AIMs can be used to estimate biogeographical ancestry at the level of the population, subgroup (e.g. cases and controls) and individual. Ancestry estimates at both the subgroup and individual level can be directly instructive regarding the genetics of the phenotypes that differ qualitatively or in frequency between populations. These estimates can provide a compelling foundation for the use of admixture mapping (AM) methods to identify the genes underlying these traits. We present details of a panel of 34 AIMs and demonstrate how such studies can proceed, by using skin pigmentation as a model phenotype. We have genotyped these markers in two population samples with primarily African ancestry, viz. African Americans from Washington D.C. and an African Caribbean sample from Britain, and in a sample of European Americans from Pennsylvania. In the two African population samples, we observed significant correlations between estimates of individual ancestry and skin pigmentation as measured by reflectometry (R-2 = 0.21, P < 0.0001 for the African-American sample and R-2 = 0.16, P < 0.0001 for the British African-Caribbean sample). These correlations confirm the validity of the ancestry estimates and also indicate the high level of population structure related to admixture, a level that characterizes these populations and that is detectable by using other tests to identify genetic structure. We have also applied two methods of admixture mapping to test for the effects of three candidate genes (TYR, OCA2, MC1R) on pigmentation. We show that TYR and OCA2 have measurable effects on skin pigmentation differences between the west African and west European parental populations. This work indicates that it is possible to estimate the individual ancestry of a person based on DNA analysis with a reasonable number of well-defined genetic markers. The implications and applications of ancestry estimates in biomedical research are discussed.