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

通过功能研究对厌食症基因进行全基因组鉴定及其对疾病发展的级联分析

• 批准号: 19101008
• 负责人: INOKO Hidetoshi
• 金额: $ 70.14万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19101008/
• 关键词: 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; GWAS; 感受性遺伝子; 疾患モデルマウス; コンタクチン; シナプトタグミン; NETO; シナプトガミン; シンタキシン; 酵母ツーハイブリッド法; ゲノムワイド相関解析(GWAS); シナプス小胞; 神経伝達物質; エンドサイトーシス

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.

饮食失调症是一种精神疾病，自20世纪90年代末以来，年轻人的饮食失调症急剧增加。然而，其治疗策略或预后方法尚未建立。在这里描述的研究中，我们首先根据我们与微卫星标记的全基因组关联分析确定了该疾病的易感基因。对鉴定的易感基因，我们应用我们的高灵敏度酵母双杂交方法，然后在哺乳动物细胞中进行免疫沉淀分析。通过这些分析，我们发现了几十个疾病相关的相互作用，其身份表明易感基因的分子功能。我们通过蛋白质-蛋白质相互作用试验进一步详细分析了其中一个易感基因，并鉴定了一个83个氨基酸的区域，该区域对于分子相互作用和细胞定位都很重要，因此是药物开发靶点的良好候选者。

项目成果

A novel system of polymorphic and diverse NK cell receptors in primates.

• DOI: 10.1371/journal.pgen.1000688
• 发表时间: 2009-10
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Averdam A;Petersen B;Rosner C;Neff J;Roos C;Eberle M;Aujard F;Münch C;Schempp W;Carrington M;Shiina T;Inoko H;Knaust F;Coggill P;Sehra H;Beck S;Abi-Rached L;Reinhardt R;Walter L
• 通讯作者: Walter L

Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6.

荟萃分析证实LCE3C_LCE3B缺失是几个族裔牛皮癣的危险因素，并发现与HLA-CW6的相互作用。

• DOI: 10.1038/jid.2010.350
• 发表时间: 2011-05
• 期刊: The Journal of investigative dermatology

Genome-wide Association Study of Normal Tension Glaucoma: Common Variants in SRBD1 and ELOVL5 Contribute to Disease Susceptibility

• DOI: 10.1016/j.ophtha.2009.12.001
• 发表时间: 2010-07-01
• 期刊: OPHTHALMOLOGY
• 影响因子: 13.7
• 作者: Meguro, Akira;Inoko, Hidetoshi;Inoko, Hidetoshi
• 通讯作者: Inoko, Hidetoshi

Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients

• 发表时间: 2009-06
• 期刊: Molecular Vision
• 影响因子: 2.2
• 作者: Yukihiro Horie;N. Kitaichi;Y. Katsuyama;Kazuhiko Yoshida;T. Miura;M. Ota;Yuri Asukata;H. Inoko;N. Mizuki;S. Ishida;S. Ohno

MHC class I A loci polymorphism and diversity in three Southeast Asian populations of cynomolgus macaque

• DOI: 10.1007/s00251-009-0390-y
• 发表时间: 2009-09-01
• 期刊: IMMUNOGENETICS
• 影响因子: 3.2
• 作者: Kita, Yuki F.;Hosomichi, Kazuyoshi;Shiina, Takashi
• 通讯作者: Shiina, Takashi