Elucidation of molecular mechanisms of neurological diseases based on genome analysis

本研究的重点是在基因组分析的基础上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。本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。为了促进家族性疾病的连锁研究，一种采用SNP微阵列的高通量连锁分析系统（SNP HiTLink）已经被开发出来，并应用于许多疾病。在单基因疾病方面，我们发现了大脑常染色体隐性动脉病变伴皮层下梗死和白质脑病（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基因。结果强调了从常见病-常见变异假说到常见病-多罕见变异假说的范式转变。

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.