UNRAVELING A COMPLEX TRAIT - THE GENETICS OF INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin-dependent diabetes mellitus (IDDM), also known as type 1 or ju venile 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 pred isposition to IDDM, and a decade ago a locus with a smaller effect was identified in the insulin-gene region. With the advent of numerous mi crosatellite markers suitable for genome screening, an additional 6 lo ci that influence susceptibility to IDDM have been reported since late 1994. This paper summarizes that progress, with particular emphasis o n research conducted by Field and associates. Some of the new loci app ear to predispose people to IDDM independently of HLA and may be impor tant factors in families with IDDM who lack strong HLA susceptibility. Other loci may interact to cause susceptibility, and specific combina tions may be especially diabetogenic. Although isolating the actual pr edisposing genes in IDDM is more difficult than isolating those involv ed in single-locus genetic disorders, the fact that the genes can be i dentified with the use of a reasonable number of families is very enco uraging for future research on other genetically complex disorders.