Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A region of linkage to type 1 diabetes has been defined on human chromosome 10p11-q11 (IDDM10; P = 0.0007) using 236 UK and 76 US affected sibpairs and a 1 cM resolution microsatellite marker map. Analysis by the transmission disequilibrium test (TDT) in 1159 families with at least one diabetic child, from the UK, the US, Norway, Sardinia and Italy provided additional support for linkage at D10S193 (P = 0.006, Pc = 0.17). Notably, 5.1 cM distal to D10S193, marker D10S588 also provided positive TDT results (P = 0.009, Pc = 0.25) but the allele under analysis was also preferentially transmitted to nonaffected siblings (P = 0.0008, Pc = 0.02). This allele was positively associated in an independent UK case control study and, importantly, was neutrally transmitted in control CEPH families. These results suggest a type 1 diabetes susceptibility locus on chromosome 10p11-q11 (provisionally designated IDDM10) and demonstrate the necessity of analysis of non affected siblings in disease families, as well as analysis of control families.
Hum Mol Genet 1997 Jul
PMID:Evidence for a type 1 diabetes susceptibility locus (IDDM10) on human chromosome 10p11-q11. 921 68

IDDM10 on chromosome 10p11-q11 has been identified as a putative diabetes susceptibility locus through affected sib-pair (ASP) linkage analysis in UK nuclear families [Davies et al., 1994: Nature 371:130-136; Reed et al., 1997: Hum Mol Genet 6:1011-1016; Mein et al., 1998: Nat Genet 19:297-300]. We extended analysis of linkage to type 1 diabetes in this region by typing a total of 61 markers in a maximum of 418 UK sib-pairs (UK418; peak MLS = 3.84). We then stratified the dataset based on analyses performed previously by both our group [Mein et al., 1998: Nat Genet 19:297-300] and others [Paterson et al., 1999: Hum Hered 49:197-204; Paterson and Petronis, 1999a: Am J Med Genet 84:15-19; Paterson and Petronis, 2000a: J Med Genet 37:186-191; Paterson and Petronis, b: Eur J Hum Genet 8:145-148] and used a permutation procedure to assess the significance of the results. We conclude that the results obtained had a high probability of occurring by chance alone. These data highlight the limitations of stratifying small datasets (n < 500) by additional criteria and the recurrent problems of multiple testing in genetic analysis.
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PMID:Limitations of stratifying sib-pair data in common disease linkage studies: an example using chromosome 10p14-10q11 in type 1 diabetes. 1240 6

In ethnic Russians, MHC (HLA) was shown to be the major locus determining the predisposition to type 1 diabetes mellitus (T1DM). To map the regions linked to T1DM, families with concordant or discordant sib pairs were selected from the Russian population of Moscow. With these families, linkage to T1DM was demonstrated for CTLA4 (IDDM12, 2q32.1-q33), which codes for a T-cell surface antigen, and PDCD2 (IDDM8, 6q25-q27), which is homologous to the mouse programmed cell death activator gene. With polymorphic microsatellites, regions 3q21-q25 (IDDM9) and 10p12.2 (IDDM10) were also linked to T1DM. Case/control and family studies of the polymorphic markers from region 11p13 revealed a new T1DM-associated locus in the vicinity of the catalase gene (CAT); linkage to this locus was not reported earlier for other populations. Diabetic polyneuropathy (DPN) proved to be associated with single-nucleotide polymorphisms Ala(-9)Val (SOD2), Arg213Gly (SOD3), and T(-262)C (CAT) and with a polymorphic microsatellite of the NOS2 promoter. Hence oxidative stress, which results from hyperglycemia, increased mitochondrial production of superoxide radicals, and insufficient activities of antioxidative enzymes, was assumed to play an important part in DPN development in T1DM. Diabetic nephropathy (DN) showed no association with the antioxidative enzyme genes. However, the association was observed for the insertion/deletion (I/D) polymorphism of ACE and the ecNOS34a/4b polymorphism of NOS3, two genes involved in controlling vascular tonicity, and for the I/D polymorphism of APOB and the epsilon 2/epsilon 3/epsilon 4 polymorphism of APOE, two genes involved in lipid transport. In addition, polymorphic microsatellites of chromosome 3q21-q25 proved to be closely associated with DN. The tightest association was established for D3S1550, carriers of allele 12 or genotype 12/14 having high risk of DN (OR = 4.85 and 6.25, respectively). Region 3q21-q25 was assumed to contain a major gene determining DN development, while the other DN-associated genes mostly affect the progression of DN.
Mol Biol (Mosk)
PMID:[Genomics of type I diabetes mellitus and its late complications]. 1504 45