Genome-wide identification of genes for anorexia and their cascade analysis on disease development by functional study

2011 Fiscal Year Final Research Report

• Project/Area Number: 19101008
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Applied genomics
• Research Institution: Tokai University
• Principal Investigator: INOKO Hidetoshi 東海大学, 医学部, 教授 (10101932)
• Co-Investigator(Kenkyū-buntansha): OKA Akira 東海大学, 医学部, 講師 (80384866) ; ENDOH Takaho 独立行政法人理化学研究所, 生命情報基盤研究部門, 研究員 (40384862) ; OHTSUKA Masato 東海大学, 医学部, 講師 (90372945) ; YOSHIHARA Eisaku 東海大学, 医学部, 准教授 (70167063) ; HIRAYAMA Noriaki 東海大学, 医学部, 教授 (70238393)
• Project Period (FY): 2007 – 2011
• Keywords: 摂食障害 / マイクロサテライト / 相関解析 / ネットワーク解析

Research Abstract

An eating disorder is a mental disorder which sharply increased since the late 1990s for people of young age. Its treatment strategies or prognostic methods, however, have yet to be established. In the study described here, we first identified susceptible genes of the disease, based on our genome-wide association analysis with microsatellite markers. To the identified susceptible genes, we applied our high-sensitivity yeast two-hybrid method, followed by immunoprecipitation analysis in mammalian cells. Through these analyses, we found dozens of disease-related interactors, identities of which suggest molecular function of the susceptible genes. We further analyzed one of the susceptible genes by protein-protein interaction assays in details and identified an 83 amino-acid region which is important for both molecular interactions and cellular localization and is, therefore, a good candidate as a drug development target.

Research Products

• [Journal Article] Current understanding of human genetics and genetic analysis of psoriasis (2012)
  • Author(s): Oka A, Mabuchi T, Ozawa A, Inoko H
  • Journal Title: J Dermatol Volume: 39 Pages: 231-241
  • Peer Reviewed
• [Journal Article] Genetic variation and hitchhiking between structurally polymorphic Alu insertions and HLA-A,-B, and-C alleles and other retroelements within the MHC class I region (2011)
  • Author(s): Kulski JK, Shigenari A, Inoko H
  • Journal Title: Tissue Antigens Volume: 78 Pages: 359-377
  • Peer Reviewed
• [Journal Article] Enforced expression of the transcription factor HOXD3 under the control of the Wnt1 regulatory element modulates cell adhesion properties in the developing mouse neural tube (2011)
  • Author(s): Taniguchi Y, Tanaka O, Sekiguchi M, Takekoshi S, Tsukamoto H, Kimura M, Imai K, Inoko H
  • Journal Title: J Anat Volume: 219 Pages: 589-600
  • Peer Reviewed
• [Journal Article] Exact break point of a 50 kb deletion 8 kb centromeric of the HLA-A locus with HLA-A 24 : 02 : the same deletion observed in other A 24 alleles and A 23 : 01 allele (2011)
  • Author(s): Mitsunaga S, Okudaira Y, Kunii N, Cui T, Hosomichi K, Oka A, Suzuki Y, Homma Y, Sato S, Inoue I, Inoko H
  • Journal Title: Immunogenetics Volume: 63 Pages: 467-474
  • Peer Reviewed
• [Journal Article] Particular human leukocyte antigen alleles are associated with biochemical traits in the Japanese population (2011)
  • Author(s): Mitsunaga S, Homma Y, Narita A, Kashiwase K, Okudaira Y, Shiina Y, Inoue I, Inoko H
  • Journal Title: Hum Immunol Volume: 72 Pages: 566-570
  • Peer Reviewed
• [Journal Article] SLA-DRB1 and-DQB1 genotyping by the PCR-SSOP-Luminex method (2011)
  • Author(s): Ando A, Shigenari A, Ota M, Sada M, Kawata H, Azuma F, Kojima-Shibata C, Nakajoh M, Suzuki K, Uenishi H, Kulski JK, Inoko H
  • Journal Title: Tissue Antigens Volume: 78 Pages: 49-55
  • Peer Reviewed
• [Journal Article] Targeted transgenesis through pronuclear injection of improved vectors into in vitro fertilized eggs (2011)
  • Author(s): Ohtsuka M, Miura H, Nakaoka H, Kimura M, Sato M, Inoko H
  • Journal Title: Transgenic Res Volume: 21 Pages: 225-226
  • Peer Reviewed
• [Journal Article] Which CIDE are you on? Apoptosis and energy metabolism (2011)
  • Author(s): Yonezawa T, Kurata R, Kimura M, Inoko H
  • Journal Title: Mol Biosyst Volume: 7 Pages: 91-110
  • Peer Reviewed
• [Journal Article] Pronuclear injection-based mouse targeted transgenesis for reproducible and highly efficient transgene expression (2010)
  • Author(s): Ohtsuka M, Ogiwara S, Miura H, Mizutani A, Warita T, Sato M, Imai K, Hozumi K, Sato T, Tanaka M, Kimura M, Inoko H
  • Journal Title: Nucleic Acids Res Volume: 38 Pages: e198
  • Peer Reviewed
• [Journal Article] TRIM39 and RNF39 are associated with Behcet's disease independently of HLA-B 51 and-A 26 (2010)
  • Author(s): Kurata R, Nakaoka H, Tajima A, Hosomichi K, Shiina T, Meguro A, Mizuki N, Ohono S, Inoue I, Inoko H
  • Journal Title: Biochem Biophys Res Commun Volume: 401 Pages: 533-537
  • Peer Reviewed
• [Journal Article] Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behcet's disease susceptibility loci (2010)
  • Author(s): Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H
  • Journal Title: Nature Genet Volume: 42 Pages: 703-706
  • Peer Reviewed
• [Journal Article] Flow cytometric identification of CD93 expression on naive T lymphocytes(CD4(+) CD45RA(+) cells) in human neonatal umbilical cord blood (2010)
  • Author(s): Ikewaki N, Yamao H, Kulski JK, Inoko H
  • Journal Title: J Clin Immunol Volume: 30 Pages: 723-733
  • Peer Reviewed
• [Journal Article] Polymorphic major histocompatibility complex class II Alu insertions at five loci and their association with HLA-DRB1 and-DQB1 in Japanese and Caucasians (2010)
  • Author(s): Kulski JK, Shigenari A, Shiina T, Inoko H
  • Journal Title: Tissue Antigens Volume: 76 Pages: 35-47
  • Peer Reviewed
• [Journal Article] Nutritional and hormonal regulation of uncoupling protein 2 (2009)
  • Author(s): Yonezawa T, Kurata R, Hosomichi K, Kono A, Kimura M, Inoko H
  • Journal Title: IUBMB Life Volume: 61 Pages: 1123-1131
  • Peer Reviewed
• [Journal Article] Trans-species polymorphism of the Mhc class II DRB-like gene in banded penguins(genus Spheniscus) (2009)
  • Author(s): Kikkawa EF, Tsuda TT, Sumiyama D, Naruse TK, Fukuda M, Kurita M, Wilson RP, LeMaho Y, Miller GD, Tsuda M, Murata K, Kulski JK, Inoko H
  • Journal Title: Immunogenetics Volume: 61 Pages: 341-352
  • Peer Reviewed
• [Journal Article] PKC Delta and Epsilon in drug targeting and therapeutics (2009)
  • Author(s): Yonezawa T, Kurata R, Kimura M, Inoko H
  • Journal Title: Recent Patents on DNA & Gene Sequences Volume: 3 Pages: 96-101
  • Peer Reviewed
• [Journal Article] Recombinant DNA technologies for construction of precisely designed transgene constructs (2009)
  • Author(s): Ohtsuka M, Kimura M, Tanaka M, Inoko H
  • Journal Title: Curr Pharm Biotechnol Volume: 10 Pages: 244-251
  • Peer Reviewed
• [Journal Article] Detecting linkage between a trait and a marker in a random mating population without pedigree record (2009)
  • Author(s): Mano S, Endo TA, Oka A, Ozawa A, Gojobori T, Inoko H
  • Journal Title: PLoS ONE Volume: 4 Pages: e4956
  • Peer Reviewed
• [Journal Article] HLA-A allele associations with viral MER9-LTR nucleotide sequences at two distinct loci within the MHC alpha block (2009)
  • Author(s): Kulski JK, Shigenari A, Shiina T, Hosomichi K, Yawata M, Inoko H
  • Journal Title: Immunogenetics Volume: 61 Pages: 257-270
  • Peer Reviewed
• [Journal Article] Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians (2008)
  • Author(s): Kimura T, Kobayashi T, Munkhbat B, Oyungerel G, Bilegtsaikhan T, Anar D, Jambaldorj J, Munkhsaikhan S, Munkhtuvshin N, Hayashi H, Oka A, Inoue I, Inoko H
  • Journal Title: Hum Genet Volume: 123 Pages: 655-660
  • Peer Reviewed
• [Journal Article] A genome-wide association scan for asthma in a general Australian population (2008)
  • Author(s): Hui J, Oka A, James A, Palmer LJ, Musk AW, Beilby J, Inoko H
  • Journal Title: Hum Genet Volume: 123 Pages: 297-306
  • Peer Reviewed
• [Journal Article] Decrease in CD93(C1qRp) expression in a human monocyte cell line(U937) treated with various apoptosis-inducing chemical substances (2007)
  • Author(s): Ikewaki N, Tamauchi H, Inoko H
  • Journal Title: Microbiol Immunol Volume: 51 Pages: 1189-1200
  • Peer Reviewed
• [Journal Article] Immunological actions of Sophyβ-Gllucan(β-1, 3-1, 6 Gulucan), currently available commercially as a health food supplement (2007)
  • Author(s): Ikewaki N, Fujii N, Onaka T, Ikewaki S, Inoko H
  • Journal Title: Microbiol Immunol Volume: 51 Pages: 861-873
  • Peer Reviewed
• [Journal Article] High-resolution mapping for essential hypertension using microsatellite markers (2007)
  • Author(s): Yatsu K, Mizuki N, Hirawa N, Oka A, Itoh N, Yamane T, Ogawa M, Shiwa T, Tabara Y, Ohno S, Soma M, Hata A, Nakao K, Ueshima H, Ogihara T, Tomoike H, Miki T, Kimura A, Mano S, Kulski JK, Umemura S, Inoko H
  • Journal Title: Hypertension Volume: 49 Pages: 446-452
  • Peer Reviewed
• [Journal Article] Microsatellite markers for genome-wide association studies (2007)
  • Author(s): Bahram S, Inoko H
  • Journal Title: Nature Reviews Genetics Volume: 8 Pages: 164
  • Peer Reviewed
• [Journal Article] A BAC-based contig map of the cynomolgus macaque(Macaca fascicularis) major histocompatibility complex genomic region (2007)
  • Author(s): Watanabe A, Shiina T, Shimizu S, Hosomichi K, Yanagiya K, Kita YF, Kimura T, Soeda E, Torii R, Ogasawara K, Kulski JK, Inoko H
  • Journal Title: Genomics Volume: 89 Pages: 402-412
  • Peer Reviewed
• [Journal Article] Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22 (2007)
  • Author(s): Kikuchi T, Naruse TK, Onizuka M, Li S, Kimura T, Oka A, Morishima Y, Kulski JK, Ichimiya S, Sato N, Inoko H
  • Journal Title: Immunogenetics Volume: 59 Pages: 99-108
  • Peer Reviewed
• [Journal Article] One-step generation of recombineering constructs by asymmetric-end ligation and negative selection (2007)
  • Author(s): Ohtsuka M, Mizutani A, Kikuti YY, Kulski JK, Sato M, Kimura M, Tanaka M, Inoko H
  • Journal Title: Anal Biochem Volume: 360 Pages: 306-308
  • Peer Reviewed
• [Presentation] Genome-wide association studies using microsatellteis identifies a new psoriaisi susceptibility locus on chromosome 6 (2010)
  • Author(s): Oka A, Hayashi H, Ozawa A, Beck S, Inoko H
  • Organizer: The 3rd Gottingen Workshop on Immunology and Immunogenetics
  • Place of Presentation: German Primate Centerゲッティンゲン(ドイツ)
  • Year and Date: 20100627-30
• [Presentation] Genome-wide association studies define IL23R/IL12RB2 and IL10 as susceptibility loci for Behcet's Disease (2010)
  • Author(s): Inoko H
  • Organizer: The 3rd Gottingen Workshop on Immunology and Immunogenetics
  • Place of Presentation: German Primate Center,ゲッティンゲン(ドイツ)
  • Year and Date: 20100627-30
• [Presentation] Genome-wide association studies using microsatellteis identifies a new psoriaisi susceptibility locus on chromosome 6 (2010)
  • Author(s): Oka A, Hayashi H, Ozawa A, Beck S, Inoko H
  • Organizer: HGM(Human Genome Meeting) Workshop
  • Place of Presentation: Le Corum,モンペリエ(フランス)
  • Year and Date: 20100518-21
• [Presentation] Identification of NFKBIL1 as a susceptible locus of rheumatoid arthritis by genome-wide association using microsatellites and its functional analysis in steoclastogenesis. Simposium "Pathogenesis and epidemiology of Intgraocular inflammation" (2009)
  • Author(s): Inoko H
  • Organizer: The 10th Congress of International Ocular Inflammation Society
  • Place of Presentation: プラハ(チェコ共和国)
  • Year and Date: 20090530-0602
• [Presentation] Comparative genome analysis of the MHC regions in primate species (2008)
  • Author(s): Shiina T, Inoko H
  • Organizer: Sattelite Sympojium of the 22nd EFI meeting "Non-human Primate Immunogenetics"
  • Place of Presentation: トゥールーズ(フランス)
  • Year and Date: 20080402-05
• [Presentation] Comparative genome analysis of the MHC regions in vertebrate species (2007)
  • Author(s): Shiina T, Inoko H
  • Organizer: Goettingen Workshop on Immunogenetics
  • Place of Presentation: German Primate Center,ゲッティンゲン(ドイツ)
  • Year and Date: 20070226-28
• [Remarks]
  • URL: http://inoko.med.u-tokai.ac.jp/
• [Remarks]
  • URL: http://www.jbirc.aist.go.jp/gdbs
• [Patent(Industrial Property Rights)] 基板上での等温増幅反応による標的塩基配列の補足及び検出方法 (2007)
  • Inventor(s): 光永滋樹、清水佐良子、猪子英俊
  • Industrial Property Rights Holder: 東海大学、ジェノダイブファーマ
  • Industrial Property Number: 特許、2007-283345
  • Filing Date: 2007-10-31