Genetic susceptibility factors in type 1 diabetes: linkage, disequilibrium and functional analyses

Curr Opin Immunol. 1998 Dec;10(6):682-9. doi: 10.1016/s0952-7915(98)80089-7.

Abstract

Continuing progress has been made in elucidating the genetic factors involved in type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]) in the past year. Two genome scans suggested additional susceptibility intervals and provided supporting evidence for several previously reported linkages. Other studies focused on the confirmation of linkage using multipoint sibpair analyses with densely spaced markers and multiethnic collections of families. Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets -probably due to a weak effect of the disease genes, genetic heterogeneity or random variation. Linkage disequilibrium mapping has become an increasingly important tool for both the confirmation and fine-mapping of susceptibility intervals, as well as identification of etiological mutations. Functional studies indicate, firstly, that the susceptible and protective HLA class II molecules HLA-DR and -DQ bind and present nonoverlapping peptides and, secondly, that the variable number of tandem repeats at the 5' end of the insulin gene (susceptibility interval IDDM2) regulates insulin expression in the thymus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Chromosome Mapping
  • Diabetes Mellitus, Type 1 / genetics*
  • Genes, MHC Class II
  • Genetic Variation
  • Humans
  • Linkage Disequilibrium*
  • Minisatellite Repeats
  • Mutation