Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an, early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studied MODY pedigree is the RW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the'RW family, we tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deam.ase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of0.00. These results indicate that the odds are >178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q.Non-insulin-dependent or type 2 diabetes mellitus (NIDDM) is a common disorder of glucose homeostasis affecting -5% of the general population. The causes of the fasting hyperglycemia and/or glucose intolerance associated with this form of diabetes are not well understood. The contribution of heredity to the development of NIDDM has been recognized for many years (1), and the high degree of concordance of NIDDM in monozygotic twin pairs (2) indicates that genetic factors play an important role in its development. Since an understanding of the molecular basis of NIDDM would elucidate the mechanisms controlling glucose homeostasis and facilitate the development of more rational therapeutic strategies, we have undertaken a linkage study of NIDDM to identify diabetes-susceptibility genes. The use of linkage strategies to identify DNA markers for NIDDM has been difficult because this disorder does not exhibit simple Mendelian recessive or dominant inheritance. In addition, because of its late age of onset, it is difficult to obtain large multigenerational families suitable for genetic studies.

No abstract

No abstract

No abstract