title: A complete genomic screen for multiple sclerosis underscores a role for the major histocompatability complex. The Multiple Sclerosis Genetics Group.
abstract: 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).
authors.affiliation: Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston 02129, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: M
authors.initials: M
authors.lastname: Ter-Minassian
authors.forename: A
authors.initials: A
authors.lastname: Bazyk
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Terwedow
authors.forename: M A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: J B
authors.initials: JB
authors.lastname: Rimmler
authors.forename: C S
authors.initials: CS
authors.lastname: Haynes
authors.forename: A D
authors.initials: AD
authors.lastname: Roses
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Shaner
authors.forename: M
authors.initials: M
authors.lastname: Menold
authors.forename: E
authors.initials: E
authors.lastname: Seboun
authors.forename: R P
authors.initials: RP
authors.lastname: Fitoussi
authors.forename: C
authors.initials: C
authors.lastname: Gartioux
authors.forename: C
authors.initials: C
authors.lastname: Reyes
authors.forename: F
authors.initials: F
authors.lastname: Ribierre
authors.forename: G
authors.initials: G
authors.lastname: Gyapay
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: S L
authors.initials: SL
authors.lastname: Hauser
authors.forename: D E
authors.initials: DE
authors.lastname: Goodkin
authors.forename: R
authors.initials: R
authors.lastname: Lincoln
authors.forename: K
authors.initials: K
authors.lastname: Usuku
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
mesh_terms: D002874:Chromosome Mapping / Q000379:methods; D002896:Chromosomes, Human, Pair 6; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008285:Major Histocompatibility Complex; D009103:Multiple Sclerosis / Q000235:genetics*; D010375:Pedigree
chemical_list: D005819:Genetic Markers