Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by HAILE, R. W
Right arrow Articles by ISELIUS, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by HAILE, R. W
Right arrow Articles by ISELIUS, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1983 Oxford University Press

review-article

Genetic Susceptibility to Multiple Sclerosis: A Review

ROBERT W HAILE*, SUSAN E HODGE{dagger} and LENNART ISELIUS{ddagger}

*School of Public Health, University of California Los Angeles, CA 90024, USA
{dagger}Mental Retardation Unit, Neuropsychiatric Institute, School of Medicine, University of California Los Angeles, CA
{ddagger}Department of Clinical Genetics, Karolinska Hospital Stockholm, Sweden

We review evidence on genetic susceptibility to multiple sclerosis provided by studies of family resemblance, migrants, twins, HLA-associations, and segregation and linkage analyses. The higher concordance rate in MZ than DZ twins and the increasing prevalence with increasing degree of kinship to propositi suggest that genetic factors are involved in the aetiology of MS. Nonetheless, the low overall twin concordance rates, the increased prevalence of MS in DZ twins over siblings, and the weight of evidence from migrant studies strongly suggest the involvement of environmental factors as well. These results can be reconciled by hypothesizing an MS susceptibility gene with reduced penetrance, where full phenotypic expression depends on critical environmental exposures.

The location of this gene in or near the HLA region is suggested by the reports of HLA-MS associations and is supported by results of formal linkage analyses. Two general hypotheses have emerged. One involves loose linkage with no heterogeneity while the other involves very tight linkage and substantial heterogeneity, ie no linkage in 25% of the pedigrees. Since the MS gene is probably not a recent mutation, the hypothesis of loose linkage requires one to postulate intense selection to maintain linkage disequilibrium. It is primarily because of this intense selection that we currently favour the hypothesis of tight linkage with heterogeneity over any single-gene hypothesis involving loose linkage, given our present biological knowledge.

Areas for future research are suggested.

Received 1 July 1982


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.