Identification of susceptibility genes of Anorexia Nervosa by GWAS

• Project/Area Number: 23390191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: International University of Health and Welfare
• Principal Investigator: KOMAKI Gen 国際医療福祉大学, 保健医療学部, 教授 (70225564)
• Co-Investigator(Kenkyū-buntansha): 岡 晃 東海大学, 付置研究所, 講師 (80384866) ; 安藤 哲也 独立行政法人国立精神・神経医療研究センター, その他部局等, その他 (50311428) ; 猪子 英俊 東海大学, 医学部, 教授 (10101932)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2011: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
• Keywords: 心療内科学 / 摂食障害 / 神経性食欲不振 / 次世代シークエンサー / エクソーム解析 / 候補遺伝子 / 神経性食欲不振症 / 摂食障害患者 / 感受性遺伝子 / ゲノムワイド相関解析 / マイクロサテライト / SNP

Research Abstract

Despite the high heritability of anorexia nervosa (AN), no causative gene has yet been pinpointed in the human genome. We tried to identify the causative genes in AN families using whole exon sequencing (exome analysis). This analysis found rare variants yielded substitution of amino acid and shared with affected individuals. Moreover, AN causative variants were likely to be accumulated at receptor genes for neurotransmitter. Of these, a rare varaint is expected to influence protein-protein interaction. Additional variants and functional analysis in the family genes will be prerequisite for future works.

Research Products

• [Journal Article] A genome-wide association study of anorexia nervosa (2014)
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• [Journal Article] Divergence of East Asians and Europeans estimated using maleand female-specific genetic markers (2014)
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• [Journal Article] HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high-throughput sequencing. (2014)
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• [Journal Article] The Japanese Genetic Research Group For Eating Disorders. Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population (2014)
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• [Journal Article] 摂食障害研究の最近の動向 (2014)
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• [Journal Article] IL12B and IL23R gene SNPs in Japanese psoriasis (2013)
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• [Journal Article] Association analysis of the HLA-C gene in Japanese alopecia areata (2013)
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• [Journal Article] Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. (2013)
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• [Journal Article] Improved loop-mediated isothermal amplification for HLA-DRB1 genotyping using RecA and a restriction enzyme for enhanced amplification specificity (2013)
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• [Journal Article] 摂食障害と遺伝子 (2013)
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• [Journal Article] Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina (2012)
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• [Journal Article] For the Japan Marrow Donor Program: Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study. (2012)
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• [Journal Article] Genetic variants on chromosome 1q41 influence ocular axial length and high myopia. (2012)
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  • Journal Title: PLoS Genet Volume: 8
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• [Journal Article] Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina. (2012)
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• [Journal Article] Study of cynomolgus monkey (Macaca fascicularis) Mhc DRB gene polymorphism in four populations. (2012)
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  • Journal Title: Immunogenetics Volume: 64 Pages: 605-614
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• [Journal Article] Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers. (2012)
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  • Journal Title: Tissue Antigens Volume: 80 Pages: 305-316
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• [Journal Article] Fluorescent transgenic mice suitable for multi-color aggregation chimera studies. (2012)
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• [Journal Article] Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk Factors of BTNL2 gene polymorphisms and HLA class II alleles. (2012)
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• [Journal Article] Pronuclear injection-based targeted transgenesis, a reliable transgene expression method in mice. (2012)
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• [Journal Article] Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1. (2012)
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• [Journal Article] 摂食障害の遺伝子研究―現状と課題 (2012)
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  • Journal Title: 医学のあゆみ Volume: 42 Pages: 640-648
• [Journal Article] No association of Brain-Derived Neurotrophic Factor Val66Met Polymorphism with Anorexla Nervosa in Japanese (2012)
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• [Journal Article] Population genetic structure of peninsular Malaysia Malay sub-ethnic groups (2012)
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• [Journal Article] A Systems Genetics Approach Provides a Bridge from Discovered Genetic Variants to Biological Pathways in Rheumatoid Arthritis (2011)
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• [Journal Article] A novel splicing variant of CADM2 as a protective transcript of psoriasis (2011)
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• [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)
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• [Journal Article] Meta-Analysis Confirms the LCE3C_LCE3B Deletion as a Risk Factor for Psoriasis in Several Ethnic Groups and Finds Interaction with HLA-Cw6 (2011)
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• [Journal Article] NFKBIL1 Confers Resistance to Experimental Autoimmune Arthritis Through the Regulation of Dendritic Cell Functions (2011)
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• [Journal Article] Investigation of Association between TLR9 Gene Polymorphisms and VKH in Japanese Patients (2011)
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• [Journal Article] Particular human leukocyte antigen alleles are associated with biochemical traits in the Japanese population (2011)
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• [Journal Article] SLA-DRB1 and -DQB1 genotyping by the PCR-SSOP-Luminex method (2011)
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• [Journal Article] Cytochrome P450 genetic polymorphisms influence the serum concentration of calcineurin inhibitors in allogeneic hematopoietic SCT recipients (2011)
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• [Journal Article] Genetic variation and hitchhiking between structurally polymorphic Alu insertions and HLA-A, -B, and -C alleles and other retroelements with in the MHC class I region (2011)
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• [Journal Article] GM-CSF-Independent CD1a Expression in Epidermal Langerhans Cells : Evidence from Human CD1A Genome-Transgenic Mice (2011)
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• [Journal Article] Current understanding of human genetics and genetic analysis of psoriasis (2011)
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• [Presentation] 教育講演3 摂食障害の生物学的基礎 (2013)
  • Author(s): 小牧 元
  • Organizer: 第17回日本摂食障害学会・学術集会
  • Place of Presentation: 神戸市産業振興センター、神戸市
  • Invited
• [Presentation] 集団減量治療におけるドロップアウトの予測因子 (2013)
  • Author(s): 澤本良子、野崎剛弘、古川智一、森田千尋、棚橋徳成、波夛伴和、小牧 元、須藤信行
  • Organizer: 第31回日本肥満症治療学会学術集会
  • Place of Presentation: 学術総合センター, 東京
  • Invited
• [Presentation] 肥満患者の睡眠時の覚醒回数は減量効果を予測する (2013)
  • Author(s): 野崎剛弘、澤本良子、古川智一、森田千尋、棚橋徳成、波夛伴和、小牧 元、須藤信行
  • Organizer: 第31回日本肥満症治療学会学術集会
  • Place of Presentation: 学術総合センター, 東京
  • Invited
• [Presentation] 摂食障害診断質問票（EDE-Q6.0）日本語版の因子構造の検討‐男女大学生を対象として‐ (2013)
  • Author(s): 三井知代、義田俊之、小牧 元
  • Organizer: 第54回日本心身医学会総会ならびに学術講演会
  • Place of Presentation: パシフィコ横浜 会議センター, 横浜
  • Invited
• [Presentation] 脂肪酸アミド加水分解酵素（FAAH）遺伝子385C/A 多型と神経性食欲不振症との関連 (2013)
  • Author(s): 安藤哲也、田村奈穂、米良貴嗣、河合啓介、武井美智子、中本智恵美、鈴木（堀田）眞理、成尾鉄朗、石川俊男、 小牧 元
  • Organizer: 第17回日本摂食障害学会・学術集会
  • Place of Presentation: 神戸市産業振興センター、神戸市
  • Invited
• [Presentation] ベーチェット病と関節リウマチの遺伝子解析「リウマチ性疾患の疾患感受性遺伝子」 (2013)
  • Author(s): 猪子英俊
  • Organizer: 第56回日本リウマチ学会総会・学術集会シンポジウム
  • Place of Presentation: グランドプリンスホテル新高輪本館及び国際館パミール
  • Invited
• [Presentation] iPS研究の前臨床試験のためのカニクイザルMHC遺伝子の多型解析. (2013)
  • Author(s): 椎名隆
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 次世代シークエンサーを用いた8桁レベルの完璧なHLA-DNAタイピング (2012)
  • Author(s): 猪子英俊
  • Organizer: 第5回輸血検査研修会
  • Place of Presentation: 兵庫県赤十字血液センター(神戸)(招待講演)
  • Year and Date: 2012-02-12
• [Presentation] 次世代シークエンサーを用いた超高解像度HLA DNAタイピング法（SS-SBT法）の開発. (2012)
  • Author(s): 尾崎有紀
  • Organizer: 日本DNA多型学会第21回学術集会
  • Place of Presentation: 京都教育文化センター
• [Presentation] 次世代シークエンサーを用いた超高解像度HLA DNAタイピング法（SS-SBT法）の開発. (2012)
  • Author(s): 尾崎有紀
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] Development of the Super high resolution Single molecule - Sequence Based Typing (SS-SBT) method at the 8-digit level without ambiguity for HLA class I genes. (2012)
  • Author(s): S Suzuki
  • Organizer: International Histocompatibility and Immunogenetics Conference 2012
  • Place of Presentation: リバプール・ＵＫ
• [Presentation] Development of Super high resolution Single molecule - Sequence Based Typing (SS-SBT) method at the 8-digit level without ambiguity in HLA classII genes. (2012)
  • Author(s): Y Ozaki
  • Organizer: International Histocompatibility and Immunogenetics Conference 2012
  • Place of Presentation: リバプール・ＵＫ
• [Presentation] ＨＬＡ研究の臨床応用を目指した８桁レベルＨＬＡタイピング法の開発 (2012)
  • Author(s): 椎名隆
  • Organizer: 第２１回日本組織適合性学会大会シンポジウム
  • Place of Presentation: 明治大学駿河台キャンパス
• [Presentation] Ion PGM シークエンサーならびにデータ自動解析法を用いたSS-SBT法の開発. (2012)
  • Author(s): 鈴木進悟
  • Organizer: 第21回日本組織適合性学会大会
  • Place of Presentation: 明治大学駿河台キャンパス
• [Presentation] 古典的HLAクラスII遺伝子における超高解像度DNAタイピング法（SS-SBT法）の開発. (2012)
  • Author(s): 尾崎有紀
  • Organizer: 第21回日本組織適合性学会大会
  • Place of Presentation: 明治大学駿河台キャンパス
• [Presentation] 日本人および韓国人集団における尋常性乾癬の遺伝学的関連解析 (2012)
  • Author(s): 岡晃
  • Organizer: 第27回日本乾癬学会学術大会
  • Place of Presentation: 朱鷲メッセ 新潟
• [Presentation] ペンギンMHC：最も原種に近いとされるコガタペンギンのMHCクラスIIDRB1様遺伝子多型 (2012)
  • Author(s): 津田とみ
  • Organizer: 第21回 日本組織適合性学会大会
  • Place of Presentation: 明治大学駿河台キャンパス
• [Presentation] Analyses on HLA genome diversity by next generation sequencing. (2012)
  • Author(s): Takashi Shiina
  • Organizer: Centennial of Hashimoto Disease International Symposium II , 30th Anniversary 22th Hot Spring Harbor Symposium, Post-Global COE International Symposium
  • Place of Presentation: ACROS FUKUOKA
• [Presentation] フィリピン産カニクイザルのMHC多型解析によるホモ接合個体の特定 (2012)
  • Author(s): 椎名 隆
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] Ion PGM シークエンサーならびに データ自動解析法を用いた超高解像度HLAタイピング法の開発 (2012)
  • Author(s): 鈴木進悟
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: マリンメッセ福岡
• [Presentation] 関節リウマチにおけるシステムズ・ゲネティクス・アプローチ～感受性遺伝子座から生物学的経路の推定 (2011)
  • Author(s): 中岡博史、崔泰林、田嶋淳、光永滋樹、猪子英俊、井ノ上逸朗
  • Organizer: 日本人類遺伝学会第56回大会、第11回東アジア人類遺伝学会日本人類遺伝学会第56回大会、第11回東アジア人類遺伝学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-11
• [Presentation] HLAアレルと強く関連する薬剤副作用因子検索のためのHLA領域のシーケンス (2011)
  • Author(s): 細道一善、椎名隆、鈴木進悟、三浦浩美、田平知子、林健志、猪子英俊、井ノ上逸朗
  • Organizer: 日本人類遺伝学会第56回大会、第11回東アジア人類遺伝学会日本人類遺伝学会第56回大会、第11回東アジア人類遺伝学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-10
• [Presentation] Eating Disorder Examination Questionnaire 6.0 Survey of 6,000 Japanese Junior High School Students (2011)
  • Author(s): Komaki G, Hasebe T, Nishimura H, Ueno M, Kodama N, Hamada T, Kikuchi H, Ando T, Tojo M, Tachimori H, Ikuno T, Maeda M
  • Organizer: The 21th World Congress on Psychosomatic Medicine
  • Place of Presentation: National Museum of Korea, Seoul/Korea
• [Presentation] Association of stress coping with eating disorder-tendencies in young Japanese women (2011)
  • Author(s): Ando T, Hasegawa Y, Kochiya Y, Ichimaru Y, Komaki G
  • Organizer: The 21th World Congress on Psychosomatic Medicine
  • Place of Presentation: National Museum of Korea, Seoul/Korea
• [Presentation] 摂食障害遺伝子解析研究協力者会議:脳由来神経栄養因子遺伝子の多型と神経性食欲不振症との関連の検討 (2011)
  • Author(s): 安藤哲也, 石川俊男, 鈴木(堀田)眞理, 成尾鉄朗, 岡部憲二郎, 中原敏博, 瀧井正人, 河合啓介, 米良貴嗣, 中本智恵美, 武井美智子, 山口力, 永田利彦, 岡本百合, 大隈和喜, 小出将則, 山中隆夫, 田村奈穂, 切池信夫, 小牧元
  • Organizer: 第52回日本心身医学会総会ならびに学術講演会
  • Place of Presentation: パシフィコ横浜、横浜
• [Presentation] 摂食障害発症の遺伝・心理社会的要因 (2011)
  • Author(s): 小牧元
  • Organizer: 第16回日本心療内科学会学術大会
  • Place of Presentation: 東京国際交流館・プラザ平成、東京
• [Presentation] 神経性食欲不振症における血漿アミノ酸濃度プロフィールの検討 (2011)
  • Author(s): 安藤哲也、田村奈穂、山本浩史、倉尚樹、小西恵、富田吉敏、田中孝幸、知場奈津子、庭瀬亜香、濱田孝、杤久保修、石川俊男、小牧元
  • Organizer: 第16回日本心療内科学会総会・学術大会
  • Place of Presentation: 東京国際交流館・プラザ平成、東京
• [Presentation] 摂食障害の遺伝子研究 (2011)
  • Author(s): 安藤哲也・小牧元
  • Organizer: 第15回日本摂食障害学会学術集会
  • Place of Presentation: 城山観光ホテル、鹿児島
• [Presentation] EDE-Q6.0から見た思春期・青年期摂食障害患者の特徴 (2011)
  • Author(s): 高橋美智子, 武久千夏, 木川恵理, 新宅可奈子, 武田剛, 小牧元, 生野照子
  • Organizer: 第15回日本摂食障害学会学術集会
  • Place of Presentation: 城山観光ホテル、鹿児島
• [Presentation] 女子大学生のダイエット経験者および気晴らし喰い経験者の心理的・身体的特徴 (2011)
  • Author(s): 安藤哲也, 東風谷祐子, 市丸雄平, 兒玉直樹, 菊地裕絵, 小牧元
  • Organizer: 15回日本摂食障害学会学術集会
  • Place of Presentation: 城山観光ホテル、鹿児島
• [Presentation] 次世代シークエンサーを用いたHLAゲノム領域の多様性解析-究極のHLAタイピングとHLAハプロクイプの塩基配列決定- (2011)
  • Author(s): 猪子英俊、鈴木進悟、細道一善、河野あずみ、田中景子、北夕紀、吉川枝里、重成敦子、田中政之、林英樹、井ノ上逸朗、椎名隆
  • Organizer: 第20回日本組織適合性学会大会
  • Place of Presentation: ツインメッセ静岡(招待講演)
• [Presentation] 次世代シークエンサーを用いたHLAクラスI遺伝子タイピング法の開発 (2011)
  • Author(s): 鈴木進悟、吉川枝里、重成敦子、光永滋樹、椎名隆、猪子英俊
  • Organizer: 第20回日本組織適合性学会大会
  • Place of Presentation: ツインメッセ静岡
• [Presentation] 日本人集団におけるHLAと生化学検査値の関連 (2011)
  • Author(s): 奥平裕子、光永滋樹、成田暁、柏背貢一、椎名豊、本間康彦、井ノ上逸朗、猪子英俊
  • Organizer: 第20回日本組織適合性学会大会
  • Place of Presentation: ツインメッセ静岡
• [Presentation] GFPuv遺伝子とTypellS制限酵素を用いた遺伝子発現ベクターの簡便な構築法とその応用 (2011)
  • Author(s): 三浦浩美、佐藤正宏、猪子英俊、大塚正人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] コモンマーモセットMHCクラスI(Caja-G)亜領域のゲノム構造解析 (2011)
  • Author(s): Azumi Kono, 椎名隆、猪子英俊
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] HLAI遺伝子における超高解像度DNAタイピング法の開発 (2011)
  • Author(s): 鈴木進悟、尾崎有紀、吉川枝里、重成敦子、光永滋樹、椎名隆、猪子英俊
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] HLAII遺伝子における超高解像度DNAタイピング法の開発 (2011)
  • Author(s): 尾崎有紀、椎名隆、鈴木進悟、吉川枝里、重成敦子、岡晃、光永滋樹、猪子英俊
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] エクソーム解析による関節リウマチ感受性遺伝子の探索 (2011)
  • Author(s): 奥平裕子、光永滋樹、國井七絵、細道一善、田中政之、林英樹、河田寿子、鈴木康夫、佐藤慎二、本間康彦、井ノ上逸朗、猪子英俊
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 最近のゲノム解析の話題「身体はゲノムの乗り物か」
  • Author(s): 猪子英俊
  • Organizer: 第2606回京都西ロータリークラブ例会（招待講演）
  • Place of Presentation: 京都リーガロイヤルクラブ
  • Invited
• [Presentation] 主要組織適合遺伝子複合体（MHC）領域のゲノム構造進化.
  • Author(s): 椎名隆
  • Organizer: 日本進化学会第14回東京大会ワークショップ「ゲノム構造進化の分子機構」
  • Place of Presentation: 首都大学東京
• [Presentation] ラブカ(Chlamydoselachus anguineus)における主要組織適合遺伝子複合体(MHC)クラスI遺伝子の特徴と他種との系統解析.
  • Author(s): 坂本 衣里
  • Organizer: 2012年度日本板鰓類研究会シンポジウム
  • Place of Presentation: 大阪海遊館「海遊館ホール」
• [Book] Ghrelin Gene Variants and Eating Disorders. In Gerald Litwack, editor: Vitamins and Hormones, Vol. 92, Burlington (2013)
  • Author(s): Ando T
  • Publisher: Academic Press