Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations - PubMed (original) (raw)

Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations

M W Smith et al. Am J Hum Genet. 2001 Nov.

Abstract

Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite delta, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide-polymorphism databases and the literature, to achieve a 3-10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans.

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Figures

Figure 1

δc values for the loci examined across the human genome, in comparisons between European Americans and African Americans (shaded triangles) and between European Americans and Hispanics (white circles). δc values are shown on the Y-axis, and chromosome position (in centimorgans) is shown on the X-axis.

Figure 2

Relationship between differences seen at individual markers in δc and LLAR (A) and STR I*(2) (B) in African Americans, along with African American versus Hispanic δc values (C).

Figure 3

Variograms of marker δc in African Americans. For each point, the X and Y coordinates represent the map distance between markers j and k on chromosome i (map location of j > map location of k) and half the squared difference of δc between the markers, respectively (Diggle et al. 1994). All possible pairs of markers <50 cM apart were examined, and those at intervals of ⩽10 cM are shown. One observation was off the scale, with a distance of 9 cM and a difference of .25. The line is the estimated kernel smoothing function.

Figure 4

Cumulative frequency distributions of differences between African Americans, Asians, Hispanics, and European Americans are shown as δc (A), LLAR (B), and optimized STR allele-collapsing statistic I*(2) (C) (Kaplan et al. 1998).

References

Electronic-Database Information

1. Laboratory of Genomic Diversity Web site, http://lgd.nci.nih.gov (for additional allele frequency data for each locus, a full set of difference statistics between the groups, and primer sequences)

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Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations - PubMed (original) (raw)