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2002 Fiscal Year Final Research Report Summary

Establishment of iSNP database and its application to genetic study of type 2 diabetes mellitus.

Research Project

Project/Area Number 12357006
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Metabolomics
Research InstitutionGUNMA UNIVERSITY

Principal Investigator

TAKEDA Jun  Gunma University, Inst. Mol. Cell. Reg., Professor, 生体調節研究所, 教授 (40270855)

Co-Investigator(Kenkyū-buntansha) HORIKAWA Yukio  Gunma University, Inst. Mol. Cell. Reg., Associate Professor, 生体調節研究所, 助教授 (10323370)
Project Period (FY) 2000 – 2002
Keywordstype 2 diabetes / MODY / insulin secretion / genetics / SNP / obesity / birth weight / association study
Research Abstract

In order to understand the pathogenesis of type 2 diabetes, it is important to understand the expression profile of the mRNAs in pancreatic islets. In the present study, we have identified a large number of non-redundant cDNAs, considerably increasing the catalog of genes expressed in human endocrine pancreas. The partial sequences (expressed sequence tags, ESTs) of 〜22,000 clones randomly selected from a cDNA library of human pancreatic islet tumors were determined and compared with those deposited in the public databases. Clustering analysis of 21,267 ESTs obtained by 3'-end sequencing of cDNA inserts generated 6,157 non-redundant sequences comprising 2,323 groups and 3,834 singletons. Nucleotide and peptide database searches using the 3'- and 5'-ESTs, respectively, show that 3,103 and 58 of these ESTs represent known human sequences or human homologs of genes identified in other species and new members of structurally related families, respectively. The sequences also were compared with the public EST databases (dbEST and EPConDB) including ESTs from pancreatic islet, insulinoma, and fetal pancreas. As the result, 3,384 genes, including 587 unique to the islets, are newly found to be expressed in human pancreatic islets. These sequences were classified on the basis of the putative protein functions encoded, and were assigned to the respective chromosome by genome database analysis. In addition, multiple intron or intragenic SNPs (iSNPs) were identified in each of the genes unique to pancreatic islets. The larger collection of human pancreatic islet-related ESTs and iSNP genetic markers should provide a better genome source for molecular studies of tissue-specific functions of endocrine pancreas as well as for genetic studies of diabetes mellitus.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] N.Tonooka, et al.: "High frequency of mutations in the HNF-1a gene(TCF1) in non-obese patients with diabetes of youth in Japanese and identification of a case of digenic"Diabetologia. 45. 1709-1712 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nishizawa, et al.: "Small heterodimer partner, an orphan nuclear receptor, augments PPARg transactivation"J.Biol.Chem.. 277. 1586-1592 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Sanyal, et al.: "Differential regulation of the orphan nuclear receptor SHP gene promoter by orphan nuclear receptor ERR isoforms"J.Biol.Chem.. 277. 1739-1748 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I.Yoshiuchi, et al.: "Identification of a gain-of-function mutation in the HNF-1b gene in a Japanese family with MODY"Diabetologia. 45. 154-155 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Saito, et al.: "Sequence analysis and expressional regulation of mRNAs encoding b-subunits of follicle-stimulating hormone and luteinizing hormone in the red-berried newt, Cynops"Biol.Reprod.. 66. 1299-1309 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Mimura, et al.: "Differential expression of two distinct vesicular glutamate transporters in the rat retina"Neuroreport. 13. 1925-1928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Mori et al.: "The Pro^<12>-Ala substitution in PPAR-γ is associated with resistance to development of diabetes in the general population : Possible involvement in impairment of insulin secretion in individuals with type 2 diabetes"Diabetes. 50. 891-894 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Nishizawa, et al.: "Small heterodimer partner, an orphan nuclear receptor, augments PPARγ transactivation."J. Biol. Chem.. 277. 1586-1592 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Sanyal, et al.: "Differential regulation of the orphan nuclear receptor SHP gene promoter by orphan nuclear receptor ERR isoforms"J. Biol. Chem.. 277. 1739-1748 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I. Yoshiuchi, et al.: "Identification of a gain-of-function mutation in the HNF-1_ gene in a Japanese family with MODY"Diabetologia. 45. 154-155 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Sanyal, et al.: "Differential regulation of the orphan nuclear receptor SHP gene promoter by orphan nuclear receptor ERR isoforms"J. Biol. Chem.. 277. 1739-1748 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Tonooka, et al.: "High frequencies of mutations in the HNF-1_ gene in non-obese patients with diabetes of youth in Japanese and identification of a case of digenic inheritance"Diabetologia. 45. 1709-1712 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Hayashi, et al.: "Secretory granule-mediated co-secretion of L-glutamate and glucagon triggers glutamatergic signal transmission in islets of Langerhans"J. Biol Chem.. 278. 1966-1974 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Q. Zhu, et al.: "T130I mutation in HNF-4_ gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type II diabetes mellitus in Japanese subjects"Diabetologia. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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