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

Publication ,  Journal Article
Haines, JL; Ter-Minassian, M; Bazyk, A; Gusella, JF; Kim, DJ; Terwedow, H; Pericak-Vance, MA; Rimmler, JB; Haynes, CS; Roses, AD; Lee, A ...
Published in: Nat Genet
August 1996

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).

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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

August 1996

Volume

13

Issue

4

Start / End Page

469 / 471

Location

United States

Related Subject Headings

  • Pedigree
  • Multiple Sclerosis
  • Major Histocompatibility Complex
  • Humans
  • Genetic Markers
  • Genetic Linkage
  • Developmental Biology
  • Chromosomes, Human, Pair 7
  • Chromosomes, Human, Pair 6
  • Chromosome Mapping
 

Citation

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Chicago
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Haines, J. L., Ter-Minassian, M., Bazyk, A., Gusella, J. F., Kim, D. J., Terwedow, H., … Oksenberg, J. R. (1996). A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group. Nat Genet, 13(4), 469–471. https://doi.org/10.1038/ng0896-469
Haines, J. L., M. Ter-Minassian, A. Bazyk, J. F. Gusella, D. J. Kim, H. Terwedow, M. A. Pericak-Vance, et al. “A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.Nat Genet 13, no. 4 (August 1996): 469–71. https://doi.org/10.1038/ng0896-469.
Haines JL, Ter-Minassian M, Bazyk A, Gusella JF, Kim DJ, Terwedow H, et al. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group. Nat Genet. 1996 Aug;13(4):469–71.
Haines, J. L., et al. “A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.Nat Genet, vol. 13, no. 4, Aug. 1996, pp. 469–71. Pubmed, doi:10.1038/ng0896-469.
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. A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group. Nat Genet. 1996 Aug;13(4):469–471.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

August 1996

Volume

13

Issue

4

Start / End Page

469 / 471

Location

United States

Related Subject Headings

  • Pedigree
  • Multiple Sclerosis
  • Major Histocompatibility Complex
  • Humans
  • Genetic Markers
  • Genetic Linkage
  • Developmental Biology
  • Chromosomes, Human, Pair 7
  • Chromosomes, Human, Pair 6
  • Chromosome Mapping