Analysis of genomic admixture in Uyghur and its implication in mapping strategy

Abstract

The Uyghur (UIG) population, settled in Xinjiang, China, is a population presenting a typical admixture of Eastern and Western anthropometric traits. We dissected its genomic structure at population level, individual level, and chromosome level by using 20,177 SNPs spanning nearly the entire chromosome 21. Our results showed that UIG was formed by two-way admixture, with 60% European ancestry and 40% East Asian ancestry. Overall linkage disequilibrium (LD) in UIG was similar to that in its parental populations represented in East Asia and Europe with regard to common alleles, and UIG manifested elevation of LD only within 500 kb and at a level of 0.1 <r(2) < 0.8 when ancestry-informative markers (AIMs) were used. The size of chromosomal segments that were derived from East Asian and European ancestries averaged 2.4 cM and 4.1 cM, respectively. Both the magnitude of LD and fragmentary ancestral chromosome segments indicated a long history of Uyghur. Under the assumption of a hybrid isolation (HI) model, we estimated that the admixture event of UIG occurred about 126 [107 approximately 146] generations ago, or 2520 [2140 approximately 2920] years ago assuming 20 years per generation. In spite of the long history and short LD of Uyghur compared with recent admixture populations such as the African-American population, we suggest that mapping by admixture LD (MALD) is still applicable in the Uyghur population but approximately 10-fold AIMs are necessary for a whole-genome scan.

Figure 1

Distribution of Marker Information for 83 AIMs

Figure 2

Principal-Coordinate-Analysis Representation of the Allele-Sharing Distance Populations included are indicated by the symbols listed in the legend. The first two axes together explain 25.8 percent of the total variation (17.57 percent by the first axis and 8.27 percent by the second), and the rest of the axes each explain less than 1.5 percent of the total variation.

Figure 3

Probability Estimations for the Number of Clusters, with Ten Randomly Selected Data Sets The ordinate shows the Ln probability corresponding to the number of clusters (K) shown on the abscissa.

Figure 4

Phylogenetic Analysis and Structure Analysis of UIG and Four HapMap Population Samples The left population tree is based on pairwise F_ST between populations, the middle plot shows admixture proportion at population level, and the right plot shows the admixture level at individual level.

Figure 5

Summary Plot of Individual Admixture Proportions The results of individual admixture proportions estimated from 83 AIMs. Each individual is represented by a single vertical line broken into two colored segments, with lengths proportional to each of the two inferred clusters. Red indicates East Asian ancestry proportion, and blue indicates European ancestry proportion. The predefined population IDs (CHB, UIG, and CEU) are presented on the abscissa. The ordinate indicates the proportion unit.

Figure 6

Posterior Distribution of the Recombination Parameter r, per Centimorgan Both the mean and median of r are 1.26, with a 90% confidence level of [1.07, 1.46], so the admixture event happened about 126 [107, 146] generations or 2520 [2140, 2920] years ago, assuming 20 years per generation.

Figure 7

Inferred Ancestral Origins of a 67.37 cM Segment of Chromosome 21 in Three Populations Each column represents a population. The first column shows 60 CEU subjects, the second column shows 40 UIG subjects, and the third column shows 45 CHB subjects. Chromosome pairs are depicted with spaces between individual subjects. The Ln of the ratio of the probability that each locus on each haplotype in each individual derived from either Asian or European ancestry was determined for each individual and coded as red (Ln Asian/European > 1.0), blue (Ln Asian/European < −1.0), or gray lines (Ln Asian/European < 1.0, > −1.0). The marker positions (Rutgers map) are depicted in the bottom of UIG plot, and are the same in the three populations.

Figure 8

Comparison of the Proportion of Marker Pairs of Different r² Levels in UIG and its Parental Populations (A) LD was calculated from markers with MAF ≥ 0.05 in each population. (B) LD was calculated from markers with MAF ≥ 0.15 in each population.

Figure 9

Comparison of the Proportion of Marker Pairs of Different r² Levels in UIG and its Parental Populations for 602 AIMs