Identification of a critical gene involved in the pathogenesis of systemic lupus erythematosus by linkage analysis and exome resequencing

• Project/Area Number: 23791179
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: KITAMURA Akiko 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (10448318)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 全身性エリテマトーデス / キャプチャー・リシークエンス

Research Abstract

Genome wide association studies have failed to identify genesthat strongly contribute to the pathogenesis of systemic lupus erythematosus (SLE) because SLE is a multifactorial disease. We found one Japanese consanguineous SLE family which consists of 3 affected and 1 unaffected sibling. To identify the underlying gene, we performed a positional cloning analysis and revealed one homozygous region (FSLE-2; 1.1Mb). Next we carried out exome resequencing in FSLE-2 region and identified a candidate gene. We are establishing a genetically modified mouse of the candidate gene to know the association of this gene with the pathogenesis of SLE.

Research Products

• [Journal Article] Manipulation of CD98 resolves type 1 diabetes in nonobese diabetic mice (2012)
  • Author(s): ian G, Arimochi H, Kitamura A, Nishida J, Li S, Kishihara K, Maekawa Y, Yasutomo K
  • Journal Title: J Immunol Volume: 188 Issue: 5 Pages: 2227-34
  • DOI: 10.4049/jimmunol.1102586
  • Peer Reviewed
• [Journal Article] Notch2 regulates the development of marginal zone B cells through Fos (2012)
  • Author(s): Iwahashi S, Maekawa Y, Nishida J, Ishifune C, Kitamura A, Arimochi H, Kataoko K, Chiba S, Shimada M, Yasutomo K
  • Journal Title: iochem Biophys Res Commun Volume: 418 Issue: 4 Pages: 701-707
  • DOI: 10.1016/j.bbrc.2012.01.082
  • Peer Reviewed
• [Journal Article] A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and lipodystrophy in humans (2011)
  • Author(s): Kitamura A, Maekawa Y, Uehara H, Izumi K, Kawachi I, Nishizawa M, Toyoshima Y, Takahashi H, Standley DM, Tanaka K, Hamazaki J, Murata S, Obara K, Toyoshima I, Yasutomo K.
  • Journal Title: J Clin Invest Volume: 121 Issue: 10 Pages: 4150-4160
  • DOI: 10.1172/jci58414
  • Peer Reviewed
• [Presentation] Candidate genetic variations in an autosomal-dominant selective immunodeficiency syndrome (2013)
  • Author(s): Akiko Kitamura, Koji Yasutomo
  • Organizer: International Symposium on Genome Science "Expanding Frontiers of Genome Science"
  • Place of Presentation: The University of Tokyo, Ito International Research Center, (東京都)
• [Presentation] 反復性発熱・結節性紅斑・脂肪萎縮を特徴とする新規自己炎症性症候群の原因遺伝子同定 (2011)
  • Author(s): 北村明子、安友康二
  • Organizer: 第114回小児科学会総会
  • Place of Presentation: グランドプリンスホテル高輪(東京都)
  • Year and Date: 2011-08-14
• [Presentation] 反復性発熱・結節性紅斑・脂肪萎縮を特徴とする新規自己炎症性症候群の原因遺伝子同定 (2011)
  • Author(s): 北村明子
  • Organizer: 日本小児科学会
  • Place of Presentation: グランドプリンスホテル高輪（東京都）