Genomic Aspects of Sporadic Neurodegenerative Diseases.
Genomic Aspects of Sporadic Neurodegenerative Diseases.
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散发性神经退行性疾病的基因组方面。
DOI：
10.1016/j.bbrc.2014.07.098
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Mitsui J and Tsuji S.
中科院分区：
文献类型：
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作者：
Noto Y;Misawa S;Mori M;Kawaguchi N;Kanai K;Shibuya K;Isose S;Nasu S;Sekiguchi Y;Beppu M;Ohmori S;Nakagawa M;Kuwabara S.;Masahiro Mori;Mitsui J and Tsuji S.
散发性神经退行性疾病本质上是复杂的，即它们涉及可能在分子水平上起作用的多种遗传和环境因素。与孟德尔遗传的疾病相反，常见的散发性神经退行性疾病的基因组特征在很大程度上仍然未知。在过去的十年中，全基因组关联的研究，采用常见的单核苷酸多态性已被密集进行，其中的理论框架是基于“常见疾病常见变异”的假设。另一种范式是在“常见病-多种罕见变异”假设下的基于序列的关联研究。由于目前的下一代测序技术使我们能够获得几乎所有的人类基因组中的变异，而不管等位基因的频率，预计基于序列的关联研究将成为主流的方法。在这篇综述中，我们简要概述了分子遗传学方法来阐明散发形式的神经退行性疾病的分子基础，包括阿尔茨海默病，帕金森病和多系统萎缩的例子。
Sporadic neurodegenerative diseases are complex in nature, that is, they involve multiple genetic and environmental factors that may play roles at the molecular level. In contrast to diseases with Mendelian inheritance, the genomic signatures of common sporadic forms of neurodegenerative diseases largely remain unknown. Over the past decade, genome-wide association studies employing common single-nucleotide polymorphisms have been intensively conducted, in which the theoretical framework is based on the “common disease–common variants” hypothesis. Another paradigm is a sequence-based association study under the “common disease–multiple rare variants” hypothesis. Because current next-generation sequencing technologies enable us to obtain virtually all the variants in human genome irrespective of allele frequencies, it is anticipated that sequence-based association studies will become the mainstream approach. In this review, we present brief overviews of molecular genetic approaches to elucidate the molecular bases of sporadic forms of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, and multiple system atrophy as examples.