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INMEGEN Team Maps Genetic Diversity in Mexican Populations

NEW YORK (GenomeWeb News) – In a paper appearing online last night in the Proceedings of the National Academy of Sciences, researchers from Mexico's National Institute of Genomic Medicine, or INMEGEN, reported on their survey of genetic diversity in Mexican populations.

As part of the Mexican Genetic Diversity Project, or MGDP, researchers assessed roughly 100,000 SNPs in hundreds of Mexican individuals from different parts of the country, focusing on admixed, Mestizo populations of Amerindian, European, and African descent. In so doing, they uncovered common alleles specific to Mexican populations as well as genetic variation and ancestry differences between Mestizo populations in different parts of Mexico.

"Today, the Proceedings of the National Academy of Sciences are publishing truly a landmark representation of the genomic variation in the Mexican populations," former Mexican Minister of Health and current Harvard School of Public Health Dean Julio Frenk, who was not directly involved in the research, said during a conference call with reporters yesterday. "It is the first time in any developing country that a local institution has been able to understand the genetic variability in its own populations."

Frenk said such research is particularly pertinent in the wake of the recent influenza outbreak in Mexico. With nearly all of the swine flu fatalities so far occurring in Mexico, he explained, it's possible that some unidentified genetic contribution in Mexican populations is involved in mediating response to the flu virus. Understanding genetic variation in Mexican populations may eventually provide a clearer picture of both infectious and common disease susceptibility in these populations, Frenk said.

The Mexican government created INMEGEN five years ago, with the goal of not only developing world class genetic research, but also training people in related fields and taking advantage of the medical applications of the human genome, INMEGEN Director Gerardo Jimenez-Sanchez, senior author on the new paper, told reporters.

"This resource will be useful to develop strategies for the genetic analysis of Mexican and related admixed populations, such as marker selection for optimal coverage of common genetic variation in [genome-wide association] and targeted association studies," Jimenez-Sanchez and his co-authors explained, "and also for the adequate application of tagging and imputation approaches and for [admixture mapping] in Mexicans and other Latino populations."

The researchers used an Affymetrix 100K SNP array to evaluate DNA samples from 300 unrelated Mestizo individuals from six states in north, south, east, west, and central Mexico. In an effort to evaluate ancestral contributions to Mestizo genomes, the team also evaluated dozens of individuals from an indigenous group — Zapotecos from Oaxaca state — as a proxy for information on ancestral populations.

Overall, the researchers found that the Mexican populations were less diverse than HapMap populations tested so far. Even so, they detected 89 common, private alleles in at least one Mestizo population that were not present in HapMap populations. Most of these seemed to be linked to Amerindian ancestry, since the Zapotecos population carried 86 common private alleles also present in Mestizos.

Using more than 1,800 ancestry informative markers, the team found support for at least four different Mestizo sub-populations with varying levels of European and Amerindian ancestry. In general, sub-populations in northern Mexico had the highest levels of European ancestry, while sub-populations in the central and coastal parts of the country that were sampled had the highest level of Amerindian ancestry.

"Our results show that genetic differences among Mexican Mestizos from different regions in Mexico are mainly because of differences in [Amerindian] and [European] contributions," Jimenez-Sanchez and his co-authors wrote.

Along with providing information about genetic variation within and between Mexican populations, the researchers noted that the study is also yielding information that may be used in future GWA studies in these and other Mexican populations, including data that should allow more accurate SNP imputation in these populations.

Data from the current study is publicly available in an MGDP database, which also includes a state-by-state breakdown of haplotype data. Along with the 100,000 SNPs evaluated in the current study, Jimenez-Sanchez said the team has since evaluated roughly 1.5 million SNPs in the same samples using Affymetrix and Illumina chips. Results from those studies will be incorporated into the database down the road.

Finally, Jimenez-Sanchez said the team is also doing re-sequencing studies aimed at finding Mexican genomic variation missed by existing microarrays. That data will not only be included in the database, but will also aid in the development of arrays that more effectively capture genetic variation in Mexico, he said.