Linkage disequilibrium in young genetically isolated Dutch population.
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.
Aulchenko
Yurii S
YS
Department of Epidemiology and Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands. i.aoultchenko@erasmusmc.nl
Heutink
Peter
P
Mackay
Ian
I
Bertoli-Avella
Aida M
AM
Pullen
Jan
J
Vaessen
Norbert
N
Rademaker
Tessa A M
TA
Sandkuijl
Lodewijk A
LA
Cardon
Lon
L
Oostra
Ben
B
van Duijn
Cornelia M
CM
D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005828:Genetics, Population; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D009426:Netherlands; D044465:White People / Q000235:genetics
D005819:Genetic Markers