A Genomewide Single-Nucleotide–Polymorphism Panel for Mexican American Admixture Mapping

详细信息    查看全文

• 作者：Chao Tian ; David A. Hinds ; Russell Shigeta ; Sharon G. Adler ; Annette Lee ; Madeleine V. Pahl ; Gabriel Silva ; John W. Belmont ; Robert L. Hanson ; William C. Knowler ; Peter K. Gregersen ; Dennis G. Ballinger ; Michael F. Seldin
• 刊名：The American Journal of Human Genetics
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：80
• 期：6
• 页码：1014-1023
• 全文大小：345 K

文摘

For admixture mapping studies in Mexican Americans (MAM), we define a genomewide single-nucleotide–polymorphism (SNP) panel that can distinguish between chromosomal segments of Amerindian (AMI) or European (EUR) ancestry. These studies used genotypes for >400,000 SNPs, defined in EUR and both Pima and Mayan AMI, to define a set of ancestry-informative markers (AIMs). The use of two AMI populations was necessary to remove a subset of SNPs that distinguished genotypes of only one AMI subgroup from EUR genotypes. The AIMs set contained 8,144 SNPs separated by a minimum of 50 kb with only three intermarker intervals >1 Mb and had EUR/AMI F_ST values >0.30 (mean F_ST=0.48) and Mayan/Pima F_ST values <0.05 (mean F_ST<0.01). Analysis of a subset of these SNP AIMs suggested that this panel may also distinguish ancestry between EUR and other disparate AMI groups, including Quechuan from South America. We show, using realistic simulation parameters that are based on our analyses of MAM genotyping results, that this panel of SNP AIMs provides good power for detecting disease-associated chromosomal segments for genes with modest ethnicity risk ratios. A reduced set of 5,287 SNP AIMs captured almost the same admixture mapping information, but smaller SNP sets showed substantial drop-off in admixture mapping information and power. The results will enable studies of type 2 diabetes, rheumatoid arthritis, and other diseases among which epidemiological studies suggest differences in the distribution of ancestry-associated susceptibility.