Overview of admixture mapping

Abstract

Admixture mapping is a powerful method of gene mapping for diseases or traits that show differential risk by ancestry. Admixture mapping has been applied most often to African Americans who trace ancestry to Europeans and West Africans. Recent developments in admixture mapping include improvements in methods to take advantage of higher densities of genetic variants, as well as extensions to admixed populations with three or more ancestral populations, such as Latino Americans. In this unit, the author outlines the key concepts of admixture mapping. The author describes several approaches for inferring local ancestry and provides strategies for performing admixture mapping depending on the study design. Finally, the author compares and contrasts linkage analysis, association analysis, and admixture mapping, with an emphasis on integrating admixture mapping and association testing.

Figure 1

The admixture process. After two generations of interbreeding between previously isolated parental populations, chromosomes in admixed individuals are mosaics of ancestry.

Figure 2

Marker density to detect all ancestry switches. The number of ancestry switches detected as a function of marker density for an individual with the median number (n = 191, solid line) or most extreme numbers (n = 35 or 737, dashed lines) of ancestry switches among 1,976 African Americans (Adeyemo et al., 2009). For admixed African Americans, high-throughput genotyping of approximately 1 million markers using commercially available microarrays is more than sufficient to extract all of the information on local ancestry.

Figure 3

Detecting excess ancestry at a disease locus. The black line represents local ancestry among controls and the red line represents local ancestry among cases. Excess local ancestry in cases but not in controls suggests the presence of a disease locus.