Research Project

Summary

There is unanimous agreement that type 1 diabetes (T1D) is a complex, autoimmune-mediated disease that results from multiple genetic risk factors and environmental factors. The incidence varies widely between populations. Canada has the third highest rate in the world, and T1D-related health care, disability, lost work, and premature deaths cost the country about $13 billion annually. While childhood T1D was uncommon before 1950, its incidence has since risen rapidly in Austria, England, Finland, Israel, Norway, and several other countries. The reasons are not clear, primarily because of poor understanding of the condition’s etiology.

This project aimed to identify key genes conferring T1D risk on humans and gain insight into the biological pathways that confer early stages in disease progression. Researchers used results from analyses of rat and mouse rodent models to compile a list of potential T1D-related genes for studies of family-based association. Leveraging recent progress in high-throughput genotyping platforms and human HapMap data, they designed a genotyping analysis to examine 176 genes from their list.

The project team’s findings will significantly increase understanding of T1D. Markers to identify at-risk individuals prior to overt disease promise tailored therapeutics.   Progress under this project led to an expanded $15-M, 4-year research effort on T1D that began in 2006, with support from Genome Canada/Ontario Genomics Institute, Celera Diagnostics, Inc., the National Institutes of Health, several European funding agencies, and team members’ research institutions.

Fast Facts

• Highlighted outcome: identification of key genes conferring T1D risk on humans and insight into the biological pathways that underlie disease progression.
• Number of research personnel:  45.
• Number of peer-reviewed publications:  13 journal articles, 1 book, and 35 invited presentations.
• Number of patents in process or obtained: 1 invention disclosure for identification of a gene potentially controlling T1D and human haematopoiesis and 1 provisional patent for three novel loci for T1D susceptibility.

Notable Publications
Ivakine EA, Gulban O, Mortin-Toth SM, Canty A, and Danska JS. 2006.  The Idd4 locus displays sex-specific epistatic effects on type 1 diabetes susceptibility in NOD mice. Diabetes 55:3611-19.

Ivakine EA, Gulban O, Mortin-Toth SM, Scott C, Spurrell D, Canty A, and Danska JS. 2006.  Molecular genetic analysis of the Idd4 locus implicates the interferon response in type 1 diabetes in susceptibility of NOD mice. J. Immunol. 176:2976-90.

Ivakine EA, Fox CJ, Mortin-Toth SM, Canty A, Walton DS, Paterson AD, Aleksa K, Ito S, and Danska JS. 2005.  Sex-specific control of type 1 diabetes pathogenesis by the Idd4 locus in the NOD mouse. J.  Immunol. 174:7129-40.

Qu H, Tessier MC, Hudson TJ, and Polychronakos C. 2005. Confirmation of the association of the R620W polymorphism in the protein tyrosine phosphatase PTPN22 with type 1 diabetes in a family based study. J.  Med.  Genet. 42:266-70.

Newhook LA, Curtis J, Hagerty D, Grant M, Paterson AD, Crumer C, Bridger T, and Parfrey P. 2004.  High incidence of childhood type 1 diabetes in the Avalon Peninsula, Newfoundland, Canada. Diabetes Care 27:885-8.