Unravelling a complex trait: the genetics of insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM), also known as type 1 or juvenile diabetes, is one of the first disorders with a complex genetic basis that researchers have begun to unravel. More than 20 years ago, the HLA region was found to contain a major locus that influences predisposition to IDDM, and a decade ago a locus with a smaller effect was identified in the insulin-gene region. With the advent of numerous microsatellite markers suitable for genome screening, an additional 6 loci that influence susceptibility to IDDM have been reported since late 1994. This paper summarizes that progress, with particular emphasis on research conducted by Field and associates. Some of the new loci appear to predispose people to IDDM independently of HLA and may be important factors in families with IDDM who lack strong HLA susceptibility. Other loci may interact to cause susceptibility, and specific combinations may be especially diabetogenic. Although isolating the actual predisposing genes in IDDM is more difficult than isolating those involved in single-locus genetic disorders, the fact that the genes can be identified with the use of a reasonable number of families is very encouraging for future research on other genetically complex disorders.