Mapping of disease-associated variants in admixed populations - PubMed (original) (raw)

Review

Mapping of disease-associated variants in admixed populations

Daniel Shriner et al. Genome Biol. 2011.

Abstract

A more refined estimation of ancestry would benefit admixture mapping and association mapping, making disease loci identification in admixed populations more powerful.

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Figures

Figure 1

Schematic representation of population stratification and admixture. Population stratification can confound analysis of the meta-population in Generation 0 if allele frequencies differ between the two parental populations. Admixed individuals are generated by interbreeding among previously isolated populations. In subsequent generations, due to the cumulative effect of meioses, ancestry switches (that is, changes in ancestry in the interval between two markers) accumulate and chromosomes become mosaics of ancestry.

Figure 2

Local and global ancestry for three unrelated admixed African American individuals. Blue indicates two chromosomes of African ancestry, red indicates two chromosomes of European ancestry, and black indicates one chromosome of African ancestry and one chromosome of European ancestry. (a) An individual with a low proportion of African ancestry is depicted. (b) An individual with similar proportions of African and European ancestry is depicted. (c) An individual with a high proportion of African ancestry is depicted. The histograms on the right indicate the genome-wide frequencies of the three local ancestry values. Global ancestry equals the average of local ancestry divided by two (to account for diploidy). Among self-identified African Americans, the proportion of African ancestry can range from 0 to 1, representing the full range of variation. The information content of the local ancestry plots on the left is considerably higher than the global ancestry summaries on the right.

Figure 3

The effect of marker density on detecting ancestry switches. The number of ancestry switches detected as a function of marker density for the individual with the largest number of ancestry switches (n = 737) among 1,976 African Americans [17]. The continuous red line indicates the sparse panel of 1,943 ancestry-informative markers [18]. The dashed red line indicates saturation at 177,000 random markers, after which more markers provide no additional information regarding the number of ancestry switches. For admixed African Americans, high-throughput genotyping of approximately 1 million markers using commercially available microarrays is sufficient to extract all of the information on local ancestry.

Figure 4

Detecting natural selection based on the distribution of ancestry switches. The expected number of ancestry switches is based on the local recombination rate, provided by phase II of the International HapMap Project [19]. The observed number of ancestry switches is based on a sample of 1,018 unrelated African Americans [17]. An excess of ancestry switches on chromosome 6p co-localizes with the major histocompatibility complex (MHC; indicated by the bar), consistent with the well-reported evidence of positive natural selection in this genomic region. Comparing the distributions of the observed and expected numbers of ancestry switches in an admixed sample can reveal genomic regions experiencing either positive natural selection (if there is an observed excess of ancestry switches) or negative natural selection (if there is an observed deficiency of ancestry switches).

References

1. Need AC, Goldstein DB. Next generation disparities in human genomics: concerns and remedies. Trends Genet. 2009;25:489–494. doi: 10.1016/j.tig.2009.09.012. - DOI - PubMed
1. McCarthy MI. Casting a wider net for diabetes susceptibility genes. Nat Genet. 2008;40:1039–1040. doi: 10.1038/ng0908-1039. - DOI - PubMed
1. Rosenberg NA, Huang L, Jewett EM, Szpiech ZA, Jankovic I, Boehnke M. Genome-wide association studies in diverse populations. Nat Rev Genet. 2010;11:356–366. - PMC - PubMed
1. Rotimi CN, Jorde LB. Ancestry and disease in the age of genomic medicine. N Engl J Med. 2010;363:1551–1558. doi: 10.1056/NEJMra0911564. - DOI - PubMed
1. Davey Smith G, Neaton JD, Wentworth D, Stamler R, Stamler J. Mortality differences between black and white men in the USA: contribution of income and other risk factors among men screened for the MRFIT. Lancet. 1998;351:934–939. - PubMed

Mapping of disease-associated variants in admixed populations - PubMed (original) (raw)