Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases.
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.
Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. kbecker@nhgri.nih.gov
K G
KG
Becker
R M
RM
Simon
J E
JE
Bailey-Wilson
B
B
Freidlin
W E
WE
Biddison
H F
HF
McFarland
J M
JM
Trent
D000818:Animals; D001249:Asthma / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D051379:Mice; D005810:Multigene Family; D009103:Multiple Sclerosis / Q000235:genetics; D011565:Psoriasis / Q000235:genetics; D051381:Rats
D005819:Genetic Markers