Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
BMC Genomics. 2010 Jul 5;11:417. doi: 10.1186/1471-2164-11-417.
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.
We developed two panels of AIMs (approximately 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 approximately 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.
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 approximately 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 approximately 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.
混合映射是一种强大的方法，可用于识别涉及人类疾病的遗传变异，该方法利用了最近混合人群中独特的基因组结构。要使用现有的已发表的祖先信息标记（AIM）面板进行混合映射，必须为每个混合研究样本和代表祖先父群体的样本重新对标记进行基因分型。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。
我们基于 Affymetrix Genome-Wide Human SNP Array 6.0 开发了两个用于非洲裔美国人混合映射的 AIM 面板（每个面板约有 2000 个标记）。这两个 AIM 面板具有良好的图谱能力，高于大约 20000 个随机标记的更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的非洲裔美国人高血压混合映射研究中。
从现有的全基因组基因型数据中开发用于混合映射的标记面板具有两个主要优势：（1）不需要进行新的基因分型，从而节省成本，（2）可以根据各种质量措施和替换标记（以最小化间隙）对标记进行过滤，而无需额外成本。精心选择的 AIM 面板比随机标记面板具有两个主要优势：（1）来自更稀疏的 AIM 面板的图谱能力高于大约 10 倍密集的随机标记面板的图谱能力，（2）可以基于来自父群体的信息对簇进行标记。利用当前技术，基于芯片的全基因组基因分型比大约 20000 个随机标记的基因分型成本更低。使用随机标记的主要优势是不存在由于选择标记而导致的确定效应。当存在或计划存在全基因组关联数据时，从 SNP 芯片基因型数据开发可用于祖先的标记面板为混合人群中的疾病基因进行混合映射提供了一个新的机会。
