A search for type 1 diabetes (T1D) genes in Sardinia

Type 1 diabetes (T1D) is a serious disease that frequently affects children and young adults. The disease results from the lack of the hormone insulin that is essential for blood sugar regulation. This insulin deficiency is a consequence of the body’s lymphocytes attack on the only cells in the body able to produce insulin efficiently: the beta cells of the pancreas. Why this auto-reactive aggression happens is not precisely known, though some genetic risk factors have been identified and environmental components may also be involved. T1D is a major health problem in the Mediterranean island of Sardinia which, together with Finland, has the highest rate of T1D in the world. This high frequency suggests that at least some of the factors involved in provoking T1D are rather common. The high number of patients facilitate the search of the genes that predispose to T1D. But it is not simply for the high disease incidence that Sardinia is so well suited to study the genetics of T1D. An even more salient feature of this isolated population is a unique and relatively homogenous genetic asset that greatly simplifies the search of the genes involved in T1D. To find these predisposing genes we propose to initially analyse some large Sardinian families with many affected cases to find those changes in the genome that are found in the affected relatives more frequently than expected by chance. These genetic similarities among affected relatives will pinpoint the portions of the genome that contain genes involved in susceptibility to the disease. Next, we will establish which of these genes are associated with the disease in the general Sardinian population; that is, genes that are differently distributed respectively in T1D patients and in non-T1D individuals. Ultimately, knowing the genes associated with the disease will reveal targets for intervention and help us toward our final aim: to prevent the disease in at-risk individuals.