A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.

Published

Journal Article

Multiple sclerosis (MS), an inflammatory autoimmune demyelinating disorder of the central nervous system, is the most common cause of acquired neurological dysfunction arising in the second to fourth decades of life. A genetic component to MS is indicated by an increased relative risk of 20-40 to siblings compared to the general population (lambda s), and an increased concordance rate in monozygotic compared to dizygotic twins. Association and/or linkage studies to candidate genes have produced many reports of significant genetic effects including those for the major histocompatability complex (MHC; particularly the HLA-DR2 allele), immunoglobulin heavy chain (IgH), T-cell receptor (TCR) and myelin basic protein (MBP) loci. With the exception of the MHC, however, these results have been difficult to replicate and/or apply beyond isolated populations. We have therefore conducted a two-stage, multi-analytical genomic screen to identify genomic regions potentially harbouring MS susceptibility genes. We genotyped 443 markers and 19 such regions were identified. These included the MHC region on 6p, the only region with a consistently reported genetic effect. However, no single locus generated overwhelming evidence of linkage. Our results suggest that a multifactorial aetiology, including both environmental and multiple genetic factors of moderate effect, is more likely than an aetiology consisting of simple mendelian disease gene(s).

Full Text

Duke Authors

Cited Authors

  • Haines, JL; Ter-Minassian, M; Bazyk, A; Gusella, JF; Kim, DJ; Terwedow, H; Pericak-Vance, MA; Rimmler, JB; Haynes, CS; Roses, AD; Lee, A; Shaner, B; Menold, M; Seboun, E; Fitoussi, RP; Gartioux, C; Reyes, C; Ribierre, F; Gyapay, G; Weissenbach, J; Hauser, SL; Goodkin, DE; Lincoln, R; Usuku, K; Oksenberg, JR

Published Date

  • August 1996

Published In

Volume / Issue

  • 13 / 4

Start / End Page

  • 469 - 471

PubMed ID

  • 8696344

Pubmed Central ID

  • 8696344

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng0896-469

Language

  • eng

Conference Location

  • United States