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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)
戸村 秀明  群馬大学, 生体調節研究所, 助手 (70217553)
西郡 秀和  日本学術振興会, 特別研究員
西郡 俊絵  日本学術振興会, 特別研究員
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥43,610,000 (Direct Cost: ¥39,500,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2002: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2001: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2000: ¥25,800,000 (Direct Cost: ¥25,800,000)
Keywordstype 2 diabetes / MODY / insulin secretion / genetics / SNP / obesity / birth weight / association study / iSNP / ヒト膵ラ氏島遺伝子 / MIN6-m9 / マイクロアレイシステム
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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Nishizawa, et al.: "Small heterodimer partner, an orphan nuclear receptor, augments PPARg transactivation"J. Biol. Chem.. 277. 1586-1592 (2002)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Mimura, et al.: "Differential expression of two distinct vesicular glutamate transporters in the rat retina"Neuroreport. 13. 1925-1928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Nishigori et al.: "Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects"Proc.Natl.Acad.Sci.USA.. 98. 575-580 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] L.Yu et al.: "Genetic variation in the hepatocyte nuclear factor (HNF)-3α gene does not contribute to maturity-onset diabetes of the young in Japanese"Horm.Metab.Res.. 33. 163-166 (2001)

    • Related Report
      2001 Annual Research Report
  • [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 type2 diabetes"Diabetes. 50. 891-894 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Aihara et al.: "Assignment of SLC17A6 (alias DNPI), the gene encoding brain/pancreatic islet-type Na^+- dependent inorganic phosphate cotransporter to human chromosome 11p14.3"Cytogenet.Cell Genet.. 92. 167-169 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Hayashi et al.: "Differentiation-associated Na^+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems"J.Biol.Chem.. 276. 43400-43406 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Nishigori, et al.: "Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects."Proc.NatI.Acad.Sci.USA.. 98. 575-580 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Q.Zhu et al.: "Identification of misssense mutations in the hepatocyte nuclear factor-3β gene in Japanese subjects with late-onset Type 2 diabetes mellitus."Diabetologia. 43. 1197-1200 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Tanaka et al.: "Identification of a novel dominant-negative mutation in the hepatocyte nuclear factor-1α gene in Japanese early-onset type 2 diabetes."Horm.Metab.Res.. 32. 373-377 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Aihara et al.: "Molecular cloning of a novel brain-type Na^+-dependent inorganic phosphate cotransporter."J.Neurochem.. 74. 2622-2625 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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