Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases

Kevin G. Becker, Richard M. Simon, Joan E. Bailey-Wilson, Boris Freidlin, William E. Biddison, Henry F. Mcfarland, Jeffrey M. Trent

Research output: Contribution to journalArticle

Abstract

Human autoimmune diseases are thought to develop through a complex combination of genetic and environmental factors. Genome-wide linkage searches of autoimmune and inflammatory/immune disorders have identified a large number of non-major histocompatibility complex loci that collectively contribute to disease susceptibility. A comparison was made of the linkage results from 23 published autoimmune or immune-mediated disease genome-wide scans. Human diseases included multiple sclerosis, Crohn's disease, familial psoriasis, asthma, and type-I diabetes (IDDM). Experimental animal disease studies included murine experimental autoimmune encephalomyelitis, rat inflammatory arthritis, rat and murine IDDM, histamine sensitization, immunity to exogenous antigens, and murine lupus (systemic lupus erythematosus; SLE). A majority (≃65%) of the human positive linkages map nonrandomly into 18 distinct clusters. Overlapping of susceptibility loci occurs between different human immune diseases and by comparing conserved regions with experimental autoimmune/immune disease models. This nonrandom clustering supports a hypothesis that, in some cases, clinically distinct autoimmune diseases may be controlled by a common set of susceptibility genes.

Original languageEnglish (US)
Pages (from-to)9979-9984
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number17
DOIs
StatePublished - Aug 18 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • General

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