Abstract
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 deaminase 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 of 0.00. These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andreone T., Fajans S., Rotwein P., Skolnick M., Permutt M. A. Insulin gene analysis in a family with maturity-onset diabetes of the young. Diabetes. 1985 Feb;34(2):108–114. doi: 10.2337/diab.34.2.108. [DOI] [PubMed] [Google Scholar]
- Barnett A. H., Eff C., Leslie R. D., Pyke D. A. Diabetes in identical twins. A study of 200 pairs. Diabetologia. 1981 Feb;20(2):87–93. doi: 10.1007/BF00262007. [DOI] [PubMed] [Google Scholar]
- Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carritt B., Litt M. Report of the committee on the genetic constitution of chromosomes 20 and 21. Cytogenet Cell Genet. 1989;51(1-4):358–371. doi: 10.1159/000132799. [DOI] [PubMed] [Google Scholar]
- Economou E. P., Bergen A. W., Warren A. C., Antonarakis S. E. The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome. Proc Natl Acad Sci U S A. 1990 Apr;87(8):2951–2954. doi: 10.1073/pnas.87.8.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elbein S. C., Borecki I., Corsetti L., Fajans S. S., Hansen A. T., Nerup J., Province M., Permutt M. A. Linkage analysis of the human insulin receptor gene and maturity onset diabetes of the young. Diabetologia. 1987 Aug;30(8):641–647. doi: 10.1007/BF00277322. [DOI] [PubMed] [Google Scholar]
- Fajans S. S. MODY--a model for understanding the pathogeneses and natural history of type II diabetes. Horm Metab Res. 1987 Dec;19(12):591–599. doi: 10.1055/s-2007-1011888. [DOI] [PubMed] [Google Scholar]
- Fajans S. S. Maturity-onset diabetes of the young (MODY). Diabetes Metab Rev. 1989 Nov;5(7):579–606. doi: 10.1002/dmr.5610050705. [DOI] [PubMed] [Google Scholar]
- Fajans S. S. Scope and heterogeneous nature of MODY. Diabetes Care. 1990 Jan;13(1):49–64. doi: 10.2337/diacare.13.1.49. [DOI] [PubMed] [Google Scholar]
- Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
- Vinik A. J., Cox N. J., Xiang K., Fajans S. S., Bell G. I. Linkage studies of maturity onset diabetes of the young--R.W. pedigree. Diabetologia. 1988 Oct;31(10):778–778. doi: 10.1007/BF00274785. [DOI] [PubMed] [Google Scholar]