Admixture: Anthropological and biomedical applications

    Studying admixture is important from a historical and anthropological perspective. Migration of individuals and populations (and subsequent mixing) has always played an important role in the evolutionary history of humans. Since the XVth century, these migrations have occurred at a more global scale. This is particularly the case for the Americas. Here, populations that were previously isolated for generations came into contact and many persons currently living in North, Central and South America can trace their ancestry to different continents. We can reconstruct and interpret this history of migrations and admixture using genetic markers. A very complete perspective can be obtained when analyzing autosomal markers, maternally transmitted mtDNA markers and Y-chromosome specific markers, which are transmitted from fathers to sons. In many cases, the maternal and paternal admixture histories are remarkably different, so including mtDNA and Y-chromosome markers can provide a much better picture than that offered by the autosomal markers. Thus, using genetic markers we can reconstruct history at the individual and population level, even in the absence of a historical record.

   In addition to the role that these studies play in understanding human migrations, it is possible to exploit the recent history of admixture to map disease genes, using a method known as admixture mapping. Admixture mapping is particularly useful to study diseases having large differences in prevalence between major population groups, such as Type 2 Diabetes or Hypertension, among others. One of the advantages of admixture mapping over alternative methods is that a substantially smaller panel of markers will be required. However, these markers have to be carefully selected. Ideally, the best markers are those showing high frequency differences between the major population groups that were involved in the admixture process. We refer to these markers are "Ancestry Informative Markers or AIMs". Due to the recent origin of our species, most of the genetic markers show low frequency differences between human populations. Only a small percentage of the markers are informative for admixture mapping. In 2007, in collaboration with Mark Shriver, from Penn State University, and Paul McKeigue, from the University of Edinburgh, among others, we developed a genome-wide admixture mapping panel for Hispanic/Latino populations, including more than 2,000 informative markers (Mao et al. 2007. Am. J. Hum. Genet. 80:1171-1178).

   Finally, AIMs panels can also be used to control for the effects of population stratification in association studies in admixed populations. With these panels, it is possible to minimize the risk of false positives in candidate gene studies, or research efforts to replicate signals observed in genome-wide association studies. In 2012, we collaborated with many researchers throughout the Americas in the development and validation of the LACE (Latin American Cancer Epidemiology Consortium) AIMs panel, which is a highly informative panel of AIMs to study the history of admixture and correct for the effect of stratification in admixed populations in the Americas (Galanter et al. 2012, PLoS Genetics 8: e1002554).

Map showing admixture contributions estimated with the LACE AIMs panel in numerous populations throughout the Americas (From Galanter et al., PLoS Genetics 8: e1002554)