Linkage disequilibrium in isolated populations: Finland and a young sub-population of Kuusamo

Abstract

Linkage disequilibrium (LD), non-random association of alleles at closely linked chromosomal loci, has been used as a tool in the identification of disease alleles, and this has led to an improved understanding of pathology in many monogenic Mendelian human diseases. We are currently moving from the mapping and identification of monogenic disease loci to attempts at identifying loci involved in predisposition to multifactorial diseases. In the selection of ascertainment strategies in the studies of these complex diseases, the extent of background LD in different populations is an important consideration. Here, we compare the extent of LD among the alleles of linked loci in a randomly ascertained sample of individuals from the Finnish population and a set of individuals ascertained from the region of Kuusamo, a small sub-population, founded some 13 generations ago, which has experienced very little subsequent immigration. Thirty-three microsatellite loci were genotyped in chromosomal regions on 13q, 19q, 21q, Xq, and Xp. The genetic diversity of these loci was determined separately in the general Finnish sample and in the Kuusamo sample. The X-chromosomal loci are characterised by higher levels of LD in the samples from Kuusamo than in the much larger (and older) general population of Finland, whereas in alleles of autosomal loci very little LD was seen in either of these two samples.

Linkage disequilibrium in young genetically isolated Dutch population

“…In four autosomal regions, LD is investigated in more detail using a denser marker map in order to investigate the potential for finemapping in this population. We compare the amount of LD observed in our study with that in previous studies of LD in young 11,14 and older 15,16 genetic isolates. To assess whether the amount and decay of LD with genetic distance observed in our study population could be explained based on our knowledge of the history of the population, we performed a simulation study and compared the results to our empirical findings.…”

“…This is also true for selected regions in older populations which were subject to genetic drift (Saami, Gavoi; Table 4). 15,16 In contrast, evaluation of these regions in older isolates, which underwent exponential expansion (Sardinia, Finland), and in the general UK population reveals much lower levels of LD. 15,16 Additionally, LD declines very fast in these populations (only for pairs of markers separated by less than 0.02y are significant results found, Table 4).…”

Genetic markers and population history: Finland revisited

“…4,5,7,13 Analyses of linkage disequilibrium are also in line with the expectations based on the demographic history scenario described above. 14,15 Curiously, however, the mtDNA diversity patterns found among Finns appear to be at odds with the Y-chromosomal variation and also with the proposed 'medical genetic' scenario of population history. The Finnish mtDNA pool is shown to harbour levels of diversity comparable with other European populations, and no significant regional differences have been observed thus far.…”

NordicDB: a Nordic pool and portal for genome-wide control data

“…For the purpose of the MDS assessment, a Finnish reference data set was included. This consists of 81 individuals, 40 individuals collected from the capital area, representing genetically general population, and 41 individuals from a Finnish isolate, late-settlement area (LSFIN, described elsewhere 17,18 ). SNPs from the Illumina Human 1M-Duo chip (Illumina, San Diego, CA, USA) and the Affymetrix Genome-Wide Human SNP Array 6.0 chip (Affymetrix, Santa Clara, CA, USA) were (Figure 1b), with a clear NW-SE gradient.…”