Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a result of advances in technology, genome searches have been carried out for susceptibility genes for type 1 diabetes in humans and in the NOD mouse. These have shown that, in the NOD mouse, diabetes susceptibility is under the control of at least ten separate chromosomal loci. In the human, in addition to HLA and INS, two new susceptibility genes have been localized, IDDM4 on chromosome 11q and IDDM5 on 6q, demonstrating the polygenic nature of type 1 diabetes and the role of HLA as the major locus. Candidate genes at these loci are the subject of current investigation. Genetic and immunological markers of disease may be of value in screening the general population for individuals at risk of developing type 1 diabetes. The predictive power of different screening strategies should be tested in order to work out the potential value to the general population of preventive therapies that are now undergoing clinical trials in high risk 'pre-diabetics'. Type 2 diabetes is genetically heterogeneous, and, since 1992, two distinct genetic subtypes have been identified. The first is defined by mutations in the GCK gene, which cause up to 60% of cases of MODY. The second, designated MIDD (maternally inherited diabetes and deafness), is defined by mutation in the mitochondrial gene for tRNA(Leu(UUR)). MIDD patients are less obese than is usual for typical type 2 diabetes, may present in early adult life or occasionally in childhood and may have been diagnosed as having autoimmune type 1 diabetes, type 2 diabetes or MODY. Typically, patients with MIDD require insulin earlier than do type 2 diabetics without mitochondrial mutations. Genetically complex diseases, such as diabetes, hypertension, cancer and coronary heart disease, are common in most populations. The approaches to the genetic analysis of diabetes outlined in this review are likely to be useful to the genetic analysis of many of these disorders. Progress in this area will have important implications for public health strategies in the next decade and beyond.
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PMID:Molecular genetics of diabetes mellitus. 757 35

Considerable data support a genetic basis to susceptibility for NIDDM, but previous analysis of candidate genes has failed to identify a major susceptibility locus. Among regions with multiple potential candidates is chromosome 11, which includes the apolipoprotein C3 cluster, muscle glycogen phosphorylase, two insulin-dependent diabetes loci, the sulfonylurea receptor, and ataxia telangiectasia. To test linkage, we initially typed 19 markers at 10- to 15-cM intervals along chromosome 11. Analyses carried out under parametric models in members of 16-19 families of northern European ancestry detected possible linkage of NIDDM to D11S916. Nonparametric methods detected possible linkage to NIDDM at D11S901, which was 5- 10 cM distant, and at D11S935, which was approximately 30 cM distant. Both D11S916 and D11S901 were near the IDDM4 locus. To further test linkage, we typed five additional markers within 5 cM of D11S916 in the initial 19 families. We also tested markers from the linked region in a second set of recently sampled additional families. Two additional markers (D11S527 and D11S534) showed possible linkage in the initial 19 families, but none of the markers were linked to NIDDM in a separate set of families from the same ethnic background. The best evidence for linkage in the combined data set of the initial 19 families and 26 additional families was at D11S534 under parametric analysis (Z = 1.20) and at D11S935 under nonparametric analysis (affected pedigree number, P = 0.0013). Our findings suggest marginal evidence for a diabetes susceptibility locus in the region between D11S901 and D11S935, with the best evidence for a locus at or near D11S935. Replication of these findings in other populations will be necessary to distinguish false-positive linkage from a true NIDDM susceptibility locus.
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PMID:Linkage studies of NIDDM with 23 chromosome 11 markers in a sample of whites of northern European descent. 859 45