Linkage disequilibrium between microsatellite markers in the Swedish Sami relative to a worldwide selection of populations

Abstract

The pattern of linkage disequilibrium (LD) is affected by a number of factors, including population demography. High LD is seen in populations with a relatively limited and constant size, presumably because of genetic drift. We have examined the extent of LD among over 300 genome-wide pattern microsatellite loci in 29 populations from around the world. The pattern of LD varied between populations, with a larger extent of LD in populations with limited size relative to larger populations. In addition, the LD between 88 less well-spaced microsatellite markers from 10 different genomic regions was examined in the Sami compared with the general Swedish population. For these markers, increased LD extending up to 5 Mb was detected in the Sami. The amount of LD also differed between the chromosomal regions. The amount of LD in the Sami makes this population suitable for the mapping of complex genetic traits.

Genetic origin of the Swedish Sami inferred from HLA class I and class II allele frequencies

“…The LD between microsatellite markers has been shown to be 2 -3 times higher in the southern Sami than in the non-Sami Swedish population, consistent with a more limited population size. 38 Interestingly, Kauppi and collegues 39 found the LD in 75 kb of MHC class II region to be similar between Sami and UK Europeans, but that many haplotypes were population specific. Our data shows that some of the HLA alleles (eg, DRB1*0801) have a much higher frequency in the northern Sami than in any other human population used for comparison.…”

A genome-wide association study for age-related hearing impairment in the Saami

“…A number of studies provide evidence that the extent of LD is much higher in the Saami as compared to that in other European populations. [20][21][22][23] This would provide an important power advantage, as higher LD leads to better genomic coverage. It has been proposed that association studies based on a map of modest marker density within a population isolate such as the Saami would provide a first rough identification of the region associated with a particular complex disease.…”

“…18,19 Several genetic studies have further suggested that the extent of linkage disequilibrium (LD) in the Saami is dramatically higher compared to that of outbred populations. [20][21][22][23] Higher levels of LD are observed in other population isolates as well. 24,25 Most of the genetic studies of genetically isolated populations were conducted involving young founder populations, in which the high extent of LD can be attributed to a founder effect.…”

Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami

“…These results indicate that the potential for 'drift mapping' , anticipated based on simulations and limited empirical data, has been greatly overestimated. 2,9,10,13,[15][16][17] Most of the cited empirical work on the extent of LD in the Saami was based on microsatellite markers. 2,10,15,16 These studies only report P-values from pairwise significance tests of LD.…”

“…12,14 Due to their demographic history, it has been suggested that the Saami offer great potential for 'drift mapping' , and hence, more economic GWASs. 2,10,13,[15][16][17] However, this has been substantiated with only very limited empirical data, most of which predate the HapMap project.…”