March 08, 2010

Genome-Wide Genotyping of Pooled Samples to assess genetic ancestry (Chiang et al. 2010)

On the left: genetic differentiation between Chinese and Japanese using 420 Ancestry Informative Markers vs. 420 random SNPs. Note that the "fuzzy" picture on B would be better resolved if a larger number of SNPs had been used.

Clean genetic separation of Japanese from other East Asians was achieved here (using 350K SNPs) and here (using 200K SNPs), with Koreans forming a bridge between the Japanese and other Mongoloids.

PLoS Genetics doi:10.1371/journal.pgen.1000866

Rapid Assessment of Genetic Ancestry in Populations of Unknown Origin by Genome-Wide Genotyping of Pooled Samples

Charleston W. K. Chiang et al.

Abstract

As we move forward from the current generation of genome-wide association (GWA) studies, additional cohorts of different ancestries will be studied to increase power, fine map association signals, and generalize association results to additional populations. Knowledge of genetic ancestry as well as population substructure will become increasingly important for GWA studies in populations of unknown ancestry. Here we propose genotyping pooled DNA samples using genome-wide SNP arrays as a viable option to efficiently and inexpensively estimate admixture proportion and identify ancestry informative markers (AIMs) in populations of unknown origin. We constructed DNA pools from African American, Native Hawaiian, Latina, and Jamaican samples and genotyped them using the Affymetrix 6.0 array. Aided by individual genotype data from the African American cohort, we established quality control filters to remove poorly performing SNPs and estimated allele frequencies for the remaining SNPs in each panel. We then applied a regression-based method to estimate the proportion of admixture in each cohort using the allele frequencies estimated from pooling and populations from the International HapMap Consortium as reference panels, and identified AIMs unique to each population. In this study, we demonstrated that genotyping pooled DNA samples yields estimates of admixture proportion that are both consistent with our knowledge of population history and similar to those obtained by genotyping known AIMs. Furthermore, through validation by individual genotyping, we demonstrated that pooling is quite effective for identifying SNPs with large allele frequency differences (i.e., AIMs) and that these AIMs are able to differentiate two closely related populations (HapMap JPT and CHB).

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