Mexican American ancestry-informative markers

[Euclides]

Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians
Heather E. Collins-Schramm1, Bill Chima1, Takanobu Morii1, Kimberly Wah1, Yolanda Figueroa1, Lindsey A. Criswell2, Robert L. Hanson3, William C. Knowler3, Gabriel Silva4, John W. Belmont5 and Michael F. Seldin1

(1) Rowe Program in Human Genetics, Departments of Biological Chemistry and Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616-8669, USA
(2) Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, San Francisco, CA 94143, USA
(3) National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ 85014, USA
(4) Obras Sociales Del Hermano Pedro, Antigua, Guatemala
(5) Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA



Abstract

Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population.

[Nordhammer]

Important excerpts:

The Mexican American (MA) population is another population for which admixture studies may be valuable. The EA and Amerindian (AI) populations are separated by approximately 35,000 years (when the Caucasoid cluster separated from the Northeast Asian/Amerindian cluster), and the MA population is the result of admixture, which began about 400 years ago with the establishment of Spanish missions (Cavalli-Sforza et al. 1988).

Populations included EA, MA, Japanese and five tribes of AI: Pima, Yavapai, Mayan, Quechuan, and Amazonian. Japanese and Amazonian typing was performed by the Marshfield Center for Medical Genetics by DNA pools as previously reported (Weber et al. 2002; also see website). All other genotyping was performed in the laboratory of M.F.S. on individual samples. Blood- or buccal-cell samples were obtained from all individuals, according to protocols and informedconsent procedures approved by institutional review boards, and were labeled with an anonymous code number. DNA samples were prepared from blood or buccal-cells as previously described (Bali et al. 1999). None of the individuals were first-degree relatives of each other, and ethnicities were self-described.

The EA and MA individuals were random volunteers from northern California.

In the MA samples, all individuals had no known parents or grandparents whom they would describe as being of direct European, AI, or African heritage.

Although individual admixture varied greatly, the majority of MA individuals have between 40–80% EA ancestry.

The MA individuals examined in this study resided in Northern California and defined themselves as Mexican American. Thus, this population is slightly different than other Hispanic populations described to date, which include individuals from Arizona and from Texas (Chakraborty and Weiss 1986; Long et al. 1991). The average admixture estimates for these MA range from 22% AI to 50% AI. MA individuals in the present study had AI contributions varying from 10 to 80% AI, suggesting that there is likely to be at least as much variability in admixture ratios within a MA sub-population as between them.

At these mixture ratios, the estimated MA population allele frequencies are within 5% of actual MA allele frequencies, using any AI population. This result, in addition to the structure analyses, suggests any of these AI populations are reasonable representatives of the parental AI population(s) that contributed to the MA population 400 years ago. It also suggests that there is little admixture from other ethnicities into today’s MA population, a conclusion supported by several studies showing 5% or less African contribution (Long et al. 1991; Tseng et al 1998). In addition, using AIMs that distinguish African populations from either EA or AI populations has similarly suggested that the African contribution is less than 5% for over 95% of the MA subjects in the current study (M.F. Seldin, unpublished data).

Despite controversy over the number of migrations that contributed to the settling of the Americas and the times that they occurred, there is essential agreement that Amerindians arose from the passage of nomadic Siberian hunters from Northeast Asia to Alaska (Cavalli-Sforza et al. 1994).