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2004 Fiscal Year Final Research Report Summary

Identification of genes associated with bronchial asthtima, atopy, schizophrenia, and abnormal serum lipid profile

Research Project

Project/Area Number 12204001
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Tsukuba

Principal Investigator

ARINAMI Tadao  University of Tsukuba, Basic Medical Scienoes, Professor, 基礎医学系, 教授 (10212648)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Emiko  University of Tsukuba, Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (40344882)
SHIMOKAWA Hiroaki  Kyushu Unviersity, faculty of Medical Sciences, Associate Professor, 大学院医学研究院, 助教授 (00235681)
Project Period (FY) 2000 – 2004
Keywordsbronchial asthma / seasonal rhinitis / atopy / schizophrenia / genome / genetic polymorphism / genetic linkage / genetic association
Research Abstract

The purpose of this project is to identify genes associated with bronchial asthma, atopic dermatitis, seasonal rhinitis, schizophrenia, abnormal serum lipid profiles, and myocardial infarction. The screening methods we used were linkage analyses of families with multiple affected members and linkage disequilibrium mapping by transmission disequilibrium tests (TDT) to pinpoint associated genes.
We found strong evidence for linkage between mite-sensitive asthma and markers on chromosome 5q33 in our Japanese families. We performed mutation screening and association analyses of genes in the 9.4-Mb human linkage region and found that the CYFIP2 gene were associated significantly with asthma. Subjects homozygous for the haplotype overtransmitted to asthma-affected offspring showed significantly increased level of CYFIP2 gene expression in lymphocytes compared with ones heterozygous for the haplotype. TNF, LTA, and LTB is located consecutively on human chromosome 6p21 region, which has been li … More nked to asthma by several genome-wide screens including us. We screened for mutations in the coding and promoter regions of genes in the TNF-LTA region and conducted a TDT. Haplotypes of the LTA/TNF linkage disequilibrium block, which were associated with transcription ability changes, were associated significantly with asthma. Our results suggest that LTA is one of the genes contributing to susceptibility to atopic asthma. We identified linkage regions of chromosomes 1p, 4q, and 9q to seasonal allergic rhinitis (SAR) against orchard grass pollens. We screened for associations and found that that SNPs in SDAD1, CXCL9; CXCL10; and CXCL11 were associated with SAR. We identified 14 genes associated with atopy. We organized the Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. With a high-density single-nucleotide-polymorphism genotyping assay, we perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. We found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 and suggestive evidence of linkage to 14q11.2, 14q11.2-q13.2, and 20p12.1-p11.2. Less

  • Research Products

    (15 results)

All 2005 2004

All Journal Article (14 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q332005

    • Author(s)
      Noguchi E, Yokouchi Y, Zhang J, Shibuya K, Shibuya A, Bannai M, Tokunaga K, Doi H, Tamari M, Shimizu M, Shirakawa T, Shibasaki M, Ichikawa K, Arinami T
    • Journal Title

      American Journal of Respiratory Critical Care Medicine 172

      Pages: 183-188

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan2005

    • Author(s)
      Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M, Migita T, Ito S, Ichikawa K, Matsui A, Arinami T
    • Journal Title

      Clinical Experimental Allergy 35

      Pages: 790-796

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis2005

    • Author(s)
      Zhang J, Noguchi E, Migita O, Yokouchi Y, Nakayama J, Shibasaki M, Arinami T
    • Journal Title

      Journal of Allergy and Clinical Immunology 115

      Pages: 548-554

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p2005

    • Author(s)
      Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y, Mineta M, Takeichi M, Yamada S, Imamura A, Ohara K, Shibuya H, Ohara K, Suzuki Y, Muratake T, Kaneko N, Someya T, Inada T, Yoshikawa T, Toyota T, Yamada K, Kojima T, Takahashi S, Osamu O, Shinkai T, Nakamura M, Fukuzako H, Hashiguchi T, Niwa SI, Ueno T, Tachikawa H, Hori T, Asada T, Nanko S, Kunugi H, Hashimoto R, Ozaki N, Iwata N, Harano M, Arai H, Ohnuma T, Kusumi I, Koyama T, Yoneda H, Fukumaki Y, Shibata H, Kaneko S, Higuchi H, Yasui-Furukori N, Numachi Y, Itokawa M, Okazaki Y; Japanese Schizophrenia Sib-Pair Linkane Group
    • Journal Title

      American Journal of Human Genetics. 77(6) : 937-944, 2005 77

      Pages: 937-944

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q33.2005

    • Author(s)
      Noguchi E, Yokouchi Y, Zhang J, Shibuya K, Shibuya A, Bannai M, Tokunaga K, Doi H, Tamari M, Shimizu M, Shirakawa T, Shibasaki M, Ichikawa K, Arinami T
    • Journal Title

      American Journal of Respiratory Critical Care Medicine. 172(2)

      Pages: 183-188

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan.2005

    • Author(s)
      Migita O, Noguchi E, Koga M, Jian Z, Shibasaki M, Migita T, Ito S, Ichikawa K, Matsui A, Arinami T
    • Journal Title

      Clinical Experimental Allergy. 35(6)

      Pages: 90-796

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association of a haplotype block spanning SDAD1 gene and CXC chemokine genes with allergic rhinitis.2005

    • Author(s)
      Zhang J, Noguchi E, Migita O, Yokouchi Y, Nakayama J, Shibasaki M, Arinami T
    • Journal Title

      Journal of Allergy and Clinical Immunology 115(3)

      Pages: 548-554

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.2005

    • Author(s)
      Arinami T, Ohtsuki T, Ishiguro H, Ujike H, Tanaka Y, Morita Y, Mineta M, Takeichi M, Yamada S, Imamura A, Ohara K, Shibuya H, Ohara K, Suzuki Y, Muratake T, Kaneko N, Someya T, Inada T, Yoshikawa T, Toyota T, Yamada K, Kojima T, Takahashi S, Osamu O, Shinkai T, Nakamura M, Fukuzako H, Hashiguchi T, Niwa SI, Ueno T, Tachikawa H, Hori T, Asada T, Nanko S, Kunugi H, Hashimoto R, Ozaki N, Iwata N, Harano M, Arai H, Ohnuma T, Kusumi I, Koyama T, Yoneda H, Fukumaki Y, Shibata H, Kaneko S, Higuchi H, Yasui-Furukori N, Numachi Y, Itokawa M, Okazaki Y ; Japanese Schizophrenia Sib-Pair Linkage Group
    • Journal Title

      American Journal of Human Genetics. 77(6)

      Pages: 937-944

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanes school-aged children2004

    • Author(s)
      Yamakawa-Kobayashi K, Yanagi H, Yu Y, Endo K, Arinami T, Hamaguchi H
    • Journal Title

      Metabolism 53

      Pages: 182-186

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population2004

    • Author(s)
      Noguchi E, Nishimura F, Fukai H, Kim JE, Ichikawa K, Shibasaki M, Arinami T
    • Journal Title

      Clinical and Experimental Allergy 34

      Pages: 177-183

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma2004

    • Author(s)
      Fukai H, Ogasawara Y, Migita O, Koga M, Ichikawa K, Shibasaki M, Arinami T, Noguchi E
    • Journal Title

      Pharmacogenetics 14

      Pages: 683-690

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Associations between serum high-density lipoprotein cholesterol or apolipoprotein AI levels and common genetic variants of the ABCA1 gene in Japanese school-aged children2004

    • Author(s)
      Yamakawa-Kobayashi K, Yanagi H, Yu Y, Endo K, Arinami T, Hamaguchi H
    • Journal Title

      Metabolism 53(2)

      Pages: 182-186

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An association study of asthma and total serum IgE levels for Toll-like receptors polymorphisms in the Japanese population.2004

    • Author(s)
      Noguchi E, Nishimura F, Fukai H, Kim JE, Ichikawa K, Shibasaki M, Arinami T
    • Journal Title

      Clinical and Experimental Allergy 34(2)

      Pages: 177-183

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma.2004

    • Author(s)
      Fukai H, Ogasawara Y, Migita O, Koga M, Ichikawa K, Shibasaki M, Arinami T, Noguchi E
    • Journal Title

      Pharmacogenetics 14(10)

      Pages: 683-690

    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] 喘息および/またはアレルギー性鼻炎の素因の評価法2004

    • Inventor(s)
      有波忠雄, 野口恵美子
    • Industrial Property Rights Holder
      有波忠雄, 野口恵美子
    • Industrial Property Number
      特許願2004-259103
    • Filing Date
      2004-09-07
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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