Development of admixture mapping panels for African Americans from commercial high-density SNP arrays
Development of admixture mapping panels for African Americans from commercial high-density SNP arrays
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DOI：
10.1186/1471-2164-11-417
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发表时间：
2010-07-05
期刊：
影响因子：
4.4
通讯作者：
Adeyemo, Adebowale
中科院分区：
文献类型：
--
作者：
Chen, Guanjie;Shriner, Daniel;Adeyemo, Adebowale
背景：混合作图是一种识别与人类疾病有关的遗传变异的有力方法，它利用了最近混合人群中独特的基因组结构。为了使用现有的已发表的祖先信息标记（AIMs）面板进行混合定位，必须对每个混合研究样本和代表祖先亲代群体的样本重新进行标记基因分型。商业芯片上密集标记数据的可用性增加，使得开发不需要预先确定标记的面板成为可能。结果：我们基于Affymetrix全基因组人类SNP阵列6.0开发了两个AIMs面板（每个类似2000个标记），用于与非洲裔美国人样本的混合定位。这两个AIM面板具有良好的地图功率，高于类似于20,000个随机标记的密集面板以及其他已发表的AIM面板。作为一个测试案例，我们将这些面板应用于华盛顿特区市区非裔美国人高血压的混合测绘研究。结论：从现有的全基因组基因型数据中开发用于混合定位的标记面板具有两个主要优势：(1)不需要重新进行基因分型，从而节省了成本；(2)可以对标记进行各种质量测量过滤，并且可以在不增加成本的情况下选择替代标记（以减少差距）。与随机标记相比，精挑细选的目标标记具有两大优势：(1)稀疏目标标记的绘制能力高于密集10倍的随机标记；(2)可以根据亲本群体的信息对聚类进行标记。以目前的技术，基于芯片的全基因组基因分型比类似于2万个随机标记的基因分型更便宜。使用随机标记的主要优点是没有选择标记过程中产生的确定效应。从SNP芯片基因型数据中开发具有祖先信息的标记面板的能力为在全基因组关联数据存在或计划中对混合群体中的疾病基因进行混合定位提供了新的机会。
Background: Admixture mapping is a powerful approach for identifying genetic variants involved in human disease that exploits the unique genomic structure in recently admixed populations. To use existing published panels of ancestry-informative markers (AIMs) for admixture mapping, markers have to be genotyped de novo for each admixed study sample and samples representing the ancestral parental populations. The increased availability of dense marker data on commercial chips has made it feasible to develop panels wherein the markers need not be predetermined.Results: We developed two panels of AIMs (similar to 2,000 markers each) based on the Affymetrix Genome-Wide Human SNP Array 6.0 for admixture mapping with African American samples. These two AIM panels had good map power that was higher than that of a denser panel of similar to 20,000 random markers as well as other published panels of AIMs. As a test case, we applied the panels in an admixture mapping study of hypertension in African Americans in the Washington, D. C. metropolitan area.Conclusions: Developing marker panels for admixture mapping from existing genome-wide genotype data offers two major advantages: (1) no de novo genotyping needs to be done, thereby saving costs, and (2) markers can be filtered for various quality measures and replacement markers (to minimize gaps) can be selected at no additional cost. Panels of carefully selected AIMs have two major advantages over panels of random markers: (1) the map power from sparser panels of AIMs is higher than that of similar to 10-fold denser panels of random markers, and (2) clusters can be labeled based on information from the parental populations. With current technology, chip-based genome-wide genotyping is less expensive than genotyping similar to 20,000 random markers. The major advantage of using random markers is the absence of ascertainment effects resulting from the process of selecting markers. The ability to develop marker panels informative for ancestry from SNP chip genotype data provides a fresh opportunity to conduct admixture mapping for disease genes in admixed populations when genome-wide association data exist or are planned.