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

Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9979-84. doi: 10.1073/pnas.95.17.9979.


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 (approximately 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.

MeSH terms

  • Animals
  • Asthma / genetics
  • Autoimmune Diseases / genetics*
  • Chromosome Mapping
  • Chromosomes, Human / genetics
  • Crohn Disease / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Disease Models, Animal
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Male
  • Mice
  • Multigene Family
  • Multiple Sclerosis / genetics
  • Psoriasis / genetics
  • Rats


  • Genetic Markers