Abstract
Maturity–onset diabetes of the young (MODY) is a subtype of non–insulin dependent diabetes mellitus, with early age of onset. MODY is genetically heterogeneous, associated with glucokinase mutations and a locus on chromosome 20q; in about 50% of cases, its genetic background is unknown. We have studied 12 families in which MODY is unlinked to either glucokinase or chromosome 20q markers, and find significant evidence for linkage with microsatellite markers on chromosome 12q, most likely within a 7 centimorgan interval bracketed by D12S86 and D12S342. The disease was estimated to be linked to this chromosome region in approximately 50% of families in a heterogeneity analysis. These MODY patients exhibit major hyperglycaemia with a severe insulin secretory defect, suggesting that the causal gene is implicated in pancreatic β–cell function.
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References
Fajans, S.S. Scope and heterogeneous nature of MODY. Diabetes Care. 13, 49–64 (1990).
Froguel, P., Velho, G., Cohen, D. & Passa, P. Strategies for the collection of sibling-pair data for genetic studies in type 2 (non insulin-dependent) diabetes mellitus. Diabetologia. 34, 685 (1991).
Bell, G.I. et al. Gene for non-Insulin dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc. natn. Acad. Sci. U.S.A. 88, 1484–1488 (1991).
Froguel, P. et al. The glucokinase locus on chromosome 7p is closely linked to early onset non insulin dependent diabetes mellitus. Nature. 356, 162–164 (1992).
Gidh-Jain, M. et al. Glucokinase mutations associated with non-insulin-dependent (Type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships. Proc. natn. Acad. Sci. U.S.A. 90, 1932–1936 (1993).
Froguel, P. et al. Familial hyperglycemia due to mutations in glucokinase: Definition of a subtype of diabetes mellitus. New Engl. J. Med. 328, 697–702 (1993).
Vaxillaire, M. et al. Search for a third susceptibility gene for maturity-onset diabetes of the young. Studies with eleven candidate genes. Diabetes. 43, 389–395 (1994).
Weissenbach, J. et al. A second-generation linkage map of the human genome. Nature. 356, 794–801 (1992).
Vignal, A. et al. A non-radioactive multiplex procedure for genotyplng of microsatellite markers. In Methods In Molecular Genetics: Gene and Chromosome Analysis (ed. Adolph, K.W.) 211–221 (Academic Press, San Diego, 1993).
Herman, W. et al. Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree. Diabetes. 43, 40–46 (1994).
Velho, G. et al. Primary pancreatic b-cell secretory defect caused by mutations in the glucokinase in kindreds of maturity onset diabetes of the young. Lancet 340, 444–448 (1992).
NIH/CEPH Collaborative group. A comprehensive genetic linkage map of the human genome. Science. 258, 67–86 (1992).
Lathrop, G.M. & Lalouel, J.M. Easy calculations of lod scores and genetic risks on small computers. Am. J. hum. Genet. 38, 460–465 (1984).
Ott, J. Human Genetic Diseases :A Practical Approach (ed. Davies, K.E.) 19–32 (IRLPcrs, Oxford, 1991).
Snedecor, G.W., Cochra, W.G., In Statistical methods (Iowa State University Press, Ames, Iowa, 1989).
Kramer, C.Y. Extension of multiple range tests to group means with unequal numbers of replications. Biometrics 12, 309–310 (1956).
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Vaxillaire, M., Boccio, V., Philippi, A. et al. A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q. Nat Genet 9, 418–423 (1995). https://doi.org/10.1038/ng0495-418
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DOI: https://doi.org/10.1038/ng0495-418
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