Saturday, May 05, 2007

Admixture maps for Hispanics

The latest issue of AJHG has three papers on admixture maps for Hispanics. Admixture mapping has previously been found to be effective in African Americans (here). For Hispanics, the most obvious application would be in mapping diabetes related genes. I wonder how many markers overlap between the three papers. The number of markers they end up using in their maps ranges from about 1,600 to 5,200 SNPs. The second paper distinguishes itself in that its' markers show large frequency differences between Native American and other ancestries, not just between Native Americans and Europeans. The third one has resolution of Native Americans from North vs. South America.

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

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, and Michael F. Seldin

Am. J. Hum. Genet., 80:1014-1023, 2007

Abstract: 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 FST values >0.30 (mean FST = 0.48) and Mayan/Pima FST values <0.05>

A Genomewide Admixture Map for Latino Populations

Alkes L. Price, Nick Patterson, Fuli Yu, David R. Cox, Alicja Waliszewska, Gavin J. McDonald, Arti Tandon, Christine Schirmer, Julie Neubauer, Gabriel Bedoya, Constanza Duque, Alberto Villegas, Maria Catira Bortolini, Francisco M. Salzano, Carla Gallo, Guido Mazzotti, Marcela Tello-Ruiz, Laura Riba, Carlos A. Aguilar-Salinas, Samuel Canizales-Quinteros, Marta Menjivar, William Klitz, Brian Henderson, Christopher A. Haiman, Cheryl Winkler, Teresa Tusie-Luna, Andrés Ruiz-Linares, and David Reich

Am. J. Hum. Genet., 80:1024-1036, 2007

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.

A Genomewide Admixture Mapping Panel for Hispanic/Latino Populations

Xianyun Mao, Abigail W. Bigham, Rui Mei, Gerardo Gutierrez, Ken M. Weiss, Tom D. Brutsaert, Fabiola Leon-Velarde, Lorna G. Moore, Enrique Vargas, Paul M. McKeigue, Mark D. Shriver, and Esteban J. Parra

Am. J. Hum. Genet., 80:1171-1178, 2007

Abstract: Admixture mapping (AM) is a promising method for the identification of genetic risk factors for complex traits and diseases showing prevalence differences among populations. Efficient application of this method requires the use of a genomewide panel of ancestry-informative markers (AIMs) to infer the population of origin of chromosomal regions in admixed individuals. Genomewide AM panels with markers showing high frequency differences between West African and European populations are already available for disease-gene discovery in African Americans. However, no such a map is yet available for Hispanic/Latino populations, which are the result of two-way admixture between Native American and European populations or of three-way admixture of Native American, European, and West African populations. Here, we report a genomewide AM panel with 2,120 AIMs showing high frequency differences between Native American and European populations. The average intermarker genetic distance is 1.7 cM. The panel was identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array, a population sample with European ancestry, a Mesoamerican sample comprising Maya and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from Bolivia and Quechua from Peru. The main criteria for marker selection were both high information content for Native American/European ancestry (measured as the standardized variance of the allele frequencies, also known as "f value") and small frequency differences between the Mesoamerican and South American samples. This genomewide AM panel will make it possible to apply AM approaches in many admixed populations throughout the Americas.

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