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Fine mapping of candidate regions identtfied by QTL analysis and functiohal analysis of candidate genes located within the QTL region

Research Project

Project/Area Number 19591053
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionThe University of Tokushima

Principal Investigator

MORITANI Maki  The University of Tokushima, 疾患ゲノム研究センター, 非常勤講師 (50301312)

Co-Investigator(Kenkyū-buntansha) ITAKURA Itakura  徳島大学, 疾患ゲノム研究センター, 教授 (60134227)
KUNIKA Kiyoshi  徳島大学, 疾患ゲノム研究センター (30396254)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords2型糖尿病 / QTL / Lepr^<ab> / サブコンジェニックマウス / 疾患関連遺伝子 / 脂肪重量 / 高脂肪食負荷 / misty遣伝子 / Lepr^<db> / 疾患感受性遺伝子 / misty遺伝子 / ハプロタイプ
Research Abstract

我国の2,000万人以上の糖尿病患者や予備群の診断と治療のために、糖尿病の疾患関連遺伝子の同定が急がれる。我々は、摂食抑制ホルモン受容体の変異体(ab)の導入により、強制的に過食し重度の2型糖尿病(T2D)を来す系統と、遺伝的背景が異なる2系統の糖尿病非発症マウスとの交配系によって得られるF2マウス集団を用いる独自のQTL解析法を確立した。これらのF2集団を対象とした継続的なQTL研究において、T2Dや肥満に関連する形質(体重、内臓脂肪重量、血糖値など)に影響を及ぼす新規T2D疾患関連候補座位を複数見出した。また、高エネルギー摂取により病態形成に強く影響する座を特定し、各QTLの作用をコンジェニックマウスを用いて生体レベルで評価した結果、体重、内臓脂肪重量に強い作用を認める2領域(4,5番染色体)を特定した。複数ラインの"サブコンジェニックマウスを用いたファインマッピング"により、5番染色体の候補領域を5Mbに限局、領域内に存在する57候補遺伝子を特定し、病態の原因を明らかにする研究を継続中である。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (38 results)

All 2009 2008 2007 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (9 results) Book (2 results) Remarks (3 results)

  • [Journal Article] Diabetic modifier QTLs in F_2 intercrosses carrying homozygous transgene of TGF-beta2008

    • Author(s)
      Suzuki T, Moritani M, 他10名
    • Journal Title

      Mamm. Genome 19

      Pages: 15-25

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lsck of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population2008

    • Author(s)
      Yamaguchi Y, Moritani M, 他13名
    • Journal Title

      BMC Med. Genet 9

      Pages: 22-33

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Txansgenic expression of amutated cyclin-dependent kinase 4(CAK4/R24C)in pancreatic beta-cells prevents progression of diabetes in db/dbmice2008

    • Author(s)
      Miyawaki K, Moritani M, 他8名
    • Journal Title

      Diabetes Res, Clin. Pract. 8

      Pages: 33-41

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Common coding variant in the TCF7L2gene and study of the association with type 2 diabetes in Japanese subjects2008

    • Author(s)
      Kunika K, Moritani M, 他9名
    • Journal Title

      J. Hum, Genet 53

      Pages: 972-982

    • NAID

      10025584810

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The association of genetic variants in Kruppel-like factor 11 and Type 2 diabetes in the Japanese population2008

    • Author(s)
      Tanahashi T, Moritani M, 他10名
    • Journal Title

      Diabet Med 25

      Pages: 19-26

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diabetic modifier QTLs in F_2 intercrosses carrying homozygous transgene of TGF-beta.2008

    • Author(s)
      Suzuki T
    • Journal Title

      Mamm. Genome 19

      Pages: 15-25

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of association of genetic variation in chromosome region 15q14-22.1 with type 2 diabetes in a Japanese population.2008

    • Author(s)
      Yamaguchi Y
    • Journal Title

      BMC Med. Genet. 9

      Pages: 22-33

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transgenic expression of a mutated cyclin-dependent kinase 4 (CDK4/R24C in pancreatic beta-cells prevents progression of diabetes in db/db mice.2008

    • Author(s)
      Miyawaki K
    • Journal Title

      Diabetes Res. Clin. Pract. 82

      Pages: 33-41

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Common coding variant in the TCF7L2 gene and study of the association with type 2 diabetes in Japanese subjects.2008

    • Author(s)
      Kunika K
    • Journal Title

      J. Hum. Genet 53

      Pages: 972-982

    • NAID

      10025584810

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The association of genetic variants in Kruppel-like factor 11 and Type 2 diabetes in the Japanese population.2008

    • Author(s)
      Tanahashi T
    • Journal Title

      Diabet Med. 25

      Pages: 19-26

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single nucleotide polymorphisms in genes encoding LKB1(STK11), TORC2 (CRTC2) and AMPK alpha2-subunit(PRKAA2) and risk of type 2 diabetes.2008

    • Author(s)
      Keshavarz P
    • Journal Title

      Mol. Genet. Metab. 9

      Pages: 200-209

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diabetic modifier QTLs in F_2 intercrosses carrying homozygous transgene of TGF-beta2008

    • Author(s)
      Suzuki T.
    • Journal Title

      Mamm.Genome 19

      Pages: 15-25

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic association of single nucleotide polymorphism in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population2007

    • Author(s)
      Moritani M, Itakura M, 他16名
    • Journal Title

      Diabetologia 50

      Pages: 1218-1227

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The frequency of the G/G genotype of resistin single nucleotide polymorphism at -420 appears to be increased in younger onset type 2 diabetes2007

    • Author(s)
      Ochi M, ltakura M, 他14名
    • Journal Title

      Diabetes 56

      Pages: 2834-2838

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] PKC412(CGP41251)modulates the proliferation and lipopalysaccharide-induced inflammatory responses of RAW 264,7 macrophages2007

    • Author(s)
      Miyatake K, Itakura M, 他6名
    • Journal Title

      Biochem. Biphys. Res. Commun 360

      Pages: 115-121

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parafibromin tuimor suppressor enhances cell growth in the cells expressing SV40 1arge T antigen2007

    • Author(s)
      Iwata T, Itakura M, 他3名
    • Journal Title

      Oncogene 26

      Pages: 6176-6183

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of sample size effect on the identification of haplotype blocks2007

    • Author(s)
      Osabe D, Moritani M, 他11名
    • Journal Title

      BMC Bioinformatics 14

      Pages: 200-210

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blod pressure levels in the Japanese population2007

    • Author(s)
      Sakamoto Y, Itakura M, 他11名
    • Journal Title

      J. Hum. Genet. 52

      Pages: 781-793

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic association of single nucleotde polymorphism in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.2007

    • Author(s)
      Moritani M.
    • Journal Title

      Diabetologia 50

      Pages: 1218-1227

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The frequency of the G/G genotype of resistion single nucleotide polymorphism at -420 appears to be increased in younger onset type 2 diabetes2007

    • Author(s)
      Ochi M.
    • Journal Title

      Diabetes 56

      Pages: 2834-2838

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PKC412(CGP41251)modulates the proliferation and lipopolysaccharide-induced inflammatory responses of RAW 264.7 macrophages.2007

    • Author(s)
      Miyatake K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 360

      Pages: 115-121

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of specifc sequence motifs in the upstream region of 242 human miRNA genes.2007

    • Author(s)
      Inouchi A.
    • Journal Title

      Comput.Biol.Chem. 31

      Pages: 207-214

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen2007

    • Author(s)
      Iwata T.
    • Journal Title

      Oncogene 26

      Pages: 6176-6183

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of sample size effect on the identificaton of haplotype blocks2007

    • Author(s)
      Osabe D.
    • Journal Title

      BMC Bioinformatics 14

      Pages: 200-210

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 分泌小胞輸送複合体exocyst complexのサブユニットであるSec8分子の脾臓B細胞の分化過程における機能の解析2008

    • Author(s)
      田口純
    • Organizer
      第38回日本免疫学会総会・学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2008-12-02
    • Related Report
      2008 Final Research Report
  • [Presentation] 分泌小胞輸送複合体exocyst complexのサブユニットであるSec8分子の脾臓B細胞の分化過程における機能の解析2008

    • Author(s)
      田口 純
    • Organizer
      日本免疫学会総会・学術集会
    • Place of Presentation
      東 京
    • Year and Date
      2008-12-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] 3p24.3-22,1領域における2型糖尿病疾患感受性遺伝子の探索および機能解析2008

    • Author(s)
      森谷眞紀
    • Organizer
      第62回国立病院総合医学会総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-11-21
    • Related Report
      2008 Final Research Report
  • [Presentation] 3p24.3-22.1領域における2型糖尿病疾患感受性遺伝子の探索および機能解析2008

    • Author(s)
      森谷 眞紀
    • Organizer
      第62回国立病院総合医学会総会
    • Place of Presentation
      東 京
    • Year and Date
      2008-11-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] 3番染色体短腕の関連解析探索により見出した日本人2型糖尿病疾患感受性ENDOGL1遺伝子の機能解析2008

    • Author(s)
      森谷眞紀
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2008-05-23
    • Related Report
      2008 Final Research Report
  • [Presentation] 3番染色体短腕の関連解析探索により見出した日本人2型糖尿病疾患感受性ENDOGL1遺伝子の機能解析2008

    • Author(s)
      森谷 眞紀
    • Organizer
      第51回日本糖尿病学会年次学術集会
    • Place of Presentation
      東 京
    • Year and Date
      2008-05-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] 日本入2型糖尿病疾患感受性候補遺伝子の網羅的関連解析およびENDOGL1遺伝子の機能解析2007

    • Author(s)
      山口裕加
    • Organizer
      第30回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-13
    • Related Report
      2008 Final Research Report
  • [Presentation] 日本人2型糖尿病疾患感受性候補遺伝子の網羅的関連解析およびENDOGLI遣伝子の同定2007

    • Author(s)
      山口 裕加
    • Organizer
      第30回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2007-12-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] 糖尿病モデルマウスのQTL解析とマウス系統間のハプロタイプ解析を用いた疾患感受性遺伝子の同定2007

    • Author(s)
      森谷眞紀
    • Organizer
      第50回日本糖尿病学会
    • Place of Presentation
      仙台サンプラザ
    • Year and Date
      2007-05-24
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Book] 新臨床内科学第9版2009

    • Author(s)
      板倉光夫
    • Publisher
      医学書院
    • Related Report
      2008 Final Research Report
  • [Book] 新臨床内科学 第9版2009

    • Author(s)
      板倉 光夫
    • Publisher
      医学 書院
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.genome.tokushima-u.ac.jp

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.genome.tokushima-u.ac.jp

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.genome.tokushima-u.ac.jp

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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