Elucidation of molecular mechanisms of neurological diseases based on genome analysis

基于基因组分析阐明神经系统疾病的分子机制

• 批准号: 17019006
• 负责人: TSUJI Shoji
• 金额: $ 500.22万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17019006/
• 关键词: ゲノム; 脳神経疾患; 遺伝子; 遺伝学; 脳・神経; 分子遺伝学; 多型解析; 神経変性疾患; 脊髄小脳変性症; 脳血管障害; 連鎖漢籍; 相関解析; 連鎖解析

This study has focused on elucidation of molecular mechanisms of neurological diseases based on genome analysis, and, eventually, to develop disease-modifying therapy for neurological diseases. This study focused on the broad range of neurological diseases ranging from single gene diseases to polygenic diseases. To facilitate the linkage study for familial diseases, a high throughput linkage analysis system (SNP HiTLink) employing SNP microarrays has been developed and applied for many diseases. Regarding single gene diseases, we have discovered the causative gene for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). For sporadic diseases, we have identified a strong disease suseceptibility gene for Parkinson disease. The result emphasizes the paradigm shift from common disease-common variants hypothesis to common disease-multiple rare variants hypothesis.

本研究的重点是基于基因组分析阐明神经系统疾病的分子机制，并最终开发神经系统疾病的疾病修饰疗法。这项研究的重点是广泛的神经系统疾病，从单基因疾病到多基因疾病。为了便于家族性疾病的连锁研究，已经开发了采用SNP微阵列的高通量连锁分析系统（SNP HiTLink）并应用于许多疾病。关于单基因疾病，我们发现了伴有皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病（CARASIL）的致病基因。对于散发性疾病，我们已经确定了帕金森病的强疾病易感性基因。结果强调了从常见病-常见变异假说到常见病-多种罕见变异假说的范式转变。

项目成果

SNP HiTLink: a high-throughput linkage analysis system employing dense SNP data.

SNP HitLink：使用密集SNP数据的高通量链接分析系统。

• DOI: 10.1186/1471-2105-10-121
• 发表时间: 2009-04-24
• 期刊: BMC bioinformatics
• 影响因子: 3
• 作者: Fukuda Y;Nakahara Y;Date H;Takahashi Y;Goto J;Miyashita A;Kuwano R;Adachi H;Nakamura E;Tsuji S
• 通讯作者: Tsuji S

Development of high-throughput microarray-based resequencing system for neurologica1 disorders and its application to molecular genetics of amyotrophic lateral sclerosis

基于高通量微阵列的神经系统疾病重测序系统的开发及其在肌萎缩侧索硬化症分子遗传学中的应用

• 发表时间: 2008
• 期刊: Arch Neurol 65
• 作者: Takahashi;Y;Seki;N;Ishiura;H;Goto;J and Tsuji;S.
• 通讯作者: S.

A novel ferritin light chain gene mutation in a Japanese family with neuroferr itinopathy : description of clinical features and implications for genotype-phenotvne correlations

日本神经铁蛋白病家族中的一种新的铁蛋白轻链基因突变：临床特征的描述和基因型-表型相关性的影响

• 期刊: Mov. Disord. (in press)
• 作者: Kubota;A;Hida;A;Ichikawa;Y;Kanazawa;I;and Tsuji;S
• 通讯作者: S

SNP Haplotype Mapping in a Small ALS Family

• DOI: 10.1371/journal.pone.0005687
• 发表时间: 2009-05-25
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Krueger, Katherine A. Dick;Tsuji, Shoji;Ranum, Laura P. W.
• 通讯作者: Ranum, Laura P. W.

Nation-Wide Survey on the Epidemiology and the Natural History of Spinocerebellar Degenerations in Japan

日本脊髓小脑变性的流行病学和自然史全国调查

• 发表时间: 2009
• 作者: Qin M;Hayashi H;Oshima K;Tahira T;Hayashi K;Kondo H.;Shoji Tsuji
• 通讯作者: Shoji Tsuji