Extensive linkage disequilibrium in small human populations in Eurasia

Abstract

The extent of linkage disequilibrium (LD) was studied in two small food-gathering populations-Evenki and Saami-and two larger food-producing populations-Finns and Swedes-in northern Eurasia. In total, 50 single-nucleotide polymorphisms (SNPs) from five genes were genotyped using real-time pyrophosphate DNA sequencing, whereas 14 microsatellites were genotyped in two X-chromosomal regions. In addition, hypervariable region I of the mtDNA was sequenced to shed light on the demographic history of the populations. The SNP data, as well as the microsatellite data, reveal extensive levels of LD in Evenki and Saami when compared to Finns and Swedes. mtDNA-sequence variation is compatible with constant population size over time in Evenki and Saami but indicates population expansion in Finns and Swedes. Furthermore, the similarity between Finns and Swedes in SNP allele- and haplotype-frequency distributions indicate that these two populations may share a recent common origin. These findings suggest that populations such as the Evenki and the Saami, rather than the Finns, may be particularly suited for the initial coarse mapping of common complex diseases.

Figure 1

LD of SNP pairs in ACE, β-globin, LPL, and Xq13.3, for the four populations studied. For each population, only SNPs where the minor allele occurs at a frequency >0.1 are shown, since other SNPs are unlikely to show significant LD with this sample size. Orders of magnitude of significance values of pairwise associations (by Fisher's exact test) are given. SNP pairs showing significant LD (P<10^-6) are shaded (red). Number 44 is the single SNP from the MX region. LD of SNP pairs in Xq13.3 is shown on the right. Interlocus LD of SNPs from Xq13.3 for Finns and Swedes was not calculated because of sample-size differences between Xq13.3 and the other loci.

Figure 2

The proportion of SNP pairs showing significant association (P<10^-6) versus distance. The pattern in each bar indicates the different populations: Evenki (diagonal lines), Saami (white), Finns (horizontal and vertical lines), and Swedes (black).

Figure 3

Relationship between mean level of LD (as measured by D′) and the distance between SNPs in ACE, β-globin, LPL, and Xq13.3 for the four populations studied.

Figure 4

Minor-allele frequencies of 50 SNPs from ACE, β-globin, LPL, MX, and Xq13.3 for the four populations studied

Figure 5

Average allele-frequency differences between pairs of populations.

Figure 6

Overview of distributions of haplotypes that occur at a frequency >0.1 in at least one population. The missing piece of each pie chart represents haplotypes that occur in frequencies <0.1 in all populations.

Figure 7

Average haplotype-frequency differences (for haplotypes occurring at a frequency >0.1 in at least one population) between populations studied.