Molecular Genetics of Type 1 Diabetes


Combinations of susceptibility genes interact with environmental modifiers to precipitate autoimmune destruction of islet beta cells and type 1 diabetes (T1D). This interaction has become increasingly penetrant in recent decades with annual increases in incidence of T1D of 3% per year and the greatest increase occurring in young children. Although the major genetic determinant the human leucocyte antigen (HLA) on chromosome 6 has been known for decades, recent advances in genetic technology coupled with deoxyribonucleic acid (DNA) collections from large cohorts of individuals with T1D and controls have resulted in an explosion of information on the genetic determinants of autoimmune diabetes. To date, more than 40 predisposing loci have been identified and hundreds are in the pipeline but the molecular effects of most remain to be determined.

Key Concepts:

  • The incidence of T1D is increasing at a rate of 3% per year.

  • Multiple susceptibility genes and environmental determinants interact to precipitate disease.

  • The HLA is currently the best genetic determinant of risk of future T1D. Improving methodologies have resulted in identification of multiple susceptibility genes.

Keywords: autoimmune; human leucocyte antigen (HLA); islet autoantibodies

Figure 1.

Geographical variation in incidence of T1D.

Figure 2.

The HLA region on chromosome 6.

Figure 3.

Chromosomal localisation of selected T1D‐associated loci.



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Further Reading

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Ye, Yi, Mehers, Kay L, and Gillespie, Kathleen M(Sep 2010) Molecular Genetics of Type 1 Diabetes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022432]