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Linkage and association analysis of susceptibility regions on chromosomes 5 and 6 in 106 Scandinavian sibling pair families with multiple sclerosis
Author(s) -
Oturai Annette,
Larsen Flemming,
Ryder Lars P.,
Madsen Hans O.,
Hillert Jan,
Fredrikson Sten,
SandbergWollheim Magnhild,
Laaksonen Mikko,
KochHenriksen Nils,
Sawcer Stephen,
Fugger Lars,
Sorensen Per S.,
Svejgaard Arne
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199910)46:4<612::aid-ana9>3.0.co;2-w
Subject(s) - genetics , microsatellite , linkage disequilibrium , biology , allele , multiple sclerosis , genetic linkage , sibling , population , human leukocyte antigen , proband , genetic marker , haplotype , genetic association , gene , genotype , mutation , medicine , single nucleotide polymorphism , immunology , antigen , psychology , developmental psychology , environmental health
In the genetically homogeneous Scandinavian population, we have investigated chromosome 5 and the HLA (human leukocyte antigen) region on chromosome 6p21 by applying linkage and association analyses on 106 white sibling pair families with multiple sclerosis. The importance of genes within the HLA region for the susceptibility of multiple sclerosis has previously been reported. More recently, findings have suggested importance of regions on chromosome 5. Half of chromosome 5 was analyzed by using 14 microsatellite markers and a susceptibility region with a maximum LOD score of 1.1 was identified. Chromosome 6 was analyzed by HLA‐DR typing and using the TNFa microsatellite marker. A peak maximum LOD score of 2.0 was found at the HLA‐DR marker. Association studies were made for all the markers, comparing 106 probands from the sibling pairs with 100 unrelated controls. None of the markers on chromosome 5 showed significant association with multiple sclerosis, whereas strong association between multiple sclerosis and DR2 was found, with an odds ratio of 3.7 ( p < 10 −5 ). It is surprising that association was not seen for any of the TNFa alleles including the 121‐bp allele, although this allele was in positive linkage disequilibrium with DR2 in both patients and controls. Our results support the existence of multiple sclerosis susceptibility loci on chromosomes 5p and 6p21.

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