Genomic Screen For MS
Underscores Role Of
Major Histocompatability Complex

The Multiple Sclerosis Genetics Group [see comment]
Nat Genet 13: 469-71 (1996)
Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston 02129, USA
UI #96331290

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, 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 Etiology, including both environmental and multiple Genetic factors of moderate effect, is more likely than an Etiology consisting of simple mendelian disease Genes.


The Multiple Sclerosis Genetics Group
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; et al

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