Linkage disequilibrium in young genetically isolated Dutch population

被引:86
作者
Aulchenko, YS
Heutink, P
Mackay, I
Bertoli-Avella, AM
Pullen, J
Vaessen, N
Rademaker, TAM
Sandkuijl, LA
Cardon, L
Oostra, B
van Duijn, CM
机构
[1] Erasmus Med Ctr, Dept Epidemiol & Biostat, Genet Epidemiol Unit, NL-3000 DR Rotterdam, Netherlands
[2] Erasmus Med Ctr, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands
[3] Russian Acad Sci, Inst Cytol & Genet, SD, Novosibirsk 630090, Russia
[4] Oxagen Ltd, Oxford, England
[5] Leiden Univ, Med Ctr, NL-2300 RA Leiden, Netherlands
[6] Wellcome Trust Ctr Human Genet, Oxford, England
关键词
population; Europe; genetic isolation; linkage disequilibrium; simulation;
D O I
10.1038/sj.ejhg.5201188
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated population identified in the Netherlands by genotyping approximately 800 Short Tandem Repeat markers distributed genomewide across 58 individuals. Several regions were analyzed further using a denser marker map. The permutation-corrected measure of LD was used for analysis. A significant ( P<0.0004) relation between LD and genetic distance on a genomewide scale was found. Distance explained 4% of the total LD variation. For fine-mapping data, distance accounted for a larger proportion of LD variation ( up to 39%). A notable similarity in the genomewide distribution of LD was revealed between this population and other young genetically isolated populations from Micronesia and Costa Rica. Our study population and experiment was simulated in silico to confirm our knowledge of the history of the population. High agreement was observed between results of analysis of simulated and empirical data. We conclude that our population shows a high level of LD similar to that demonstrated previously in other young genetic isolates. In Europe, there may be a large number of young genetically isolated populations that are similar in history to ours. In these populations, a similar degree of LD is expected and thus they may be effectively used for linkage or LD mapping.
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页码:527 / 534
页数:8
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