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Multiple sclerosis and the HLA-D region: linkage and association studies

Kellar-Wood, H. F., Wood, N. W., Holmans, Peter Alan, Clayton, D., Robertson, Neil and Compston, D. A. 1995. Multiple sclerosis and the HLA-D region: linkage and association studies. Journal of Neuroimmunology 58 (2) , pp. 183-190. 10.1016/0165-5728(95)00015-T

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Abstract

Inheritance patterns of multiple sclerosis (MS) in multiplex families suggest a complex aetiology involving environmental and genetically determined components. The association between the HLA class II DR15, DQ6, Dw2 haplotype and MS has been well documented in patients with ancestral origins in Northern Europe. Conversely, linkage analysis of this region in multiplex families, derived from a population base, has generated negative results. Thus, given the Dw2 specificity association, evidence implicating this locus in disease susceptibility appears contradictory. We have collected and determined the HLA-DR and -DQ haplotypes of 115 sibling pairs with multiple sclerosis, and confirm a significant association with the Dw2-associated haplotype, both in index cases and their affected siblings compared with controls. However, using a sibling pair linkage analysis that restricts haplotype sharing probabilities to defined genetic models, we have not observed linkage of this region to susceptibility in MS. We discuss the basis for association and linkage and conclude that the DR15, DQ6, Dw2 haplotype does represent a susceptibility locus but its contribution to the pathogenesis is small; although it may interact epistatically with other susceptibility genes, this haplotype is not necessary for disease expression.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0165-5728
Last Modified: 21 Jun 2019 20:16
URI: http://orca.cf.ac.uk/id/eprint/82273

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