肌萎缩侧索硬化症的遗传病因：带来新机遇与挑战的新基因分析方法
Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges.
作者信息
Marangi Giuseppe, Traynor Bryan J
机构信息
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Institute of Medical Genetics, Catholic University, Roma, Italy.
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
出版信息
Brain Res. 2015 May 14;1607:75-93. doi: 10.1016/j.brainres.2014.10.009. Epub 2014 Oct 12.
Abstract
The genetic architecture of amyotrophic lateral sclerosis (ALS) is being increasingly understood. In this far-reaching review, we examine what is currently known about ALS genetics and how these genes were initially identified. We also discuss the various types of mutations that might underlie this fatal neurodegenerative condition and outline some of the strategies that might be useful in untangling them. These include expansions of short repeat sequences, common and low-frequency genetic variations, de novo mutations, epigenetic changes, somatic mutations, epistasis, oligogenic and polygenic hypotheses. This article is part of a Special Issue entitled ALS complex pathogenesis.
摘要
肌萎缩侧索硬化症（ALS）的遗传结构正逐渐为人所知。在这篇影响深远的综述中，我们审视了目前关于ALS遗传学的已知信息以及这些基因最初是如何被鉴定出来的。我们还讨论了可能是这种致命神经退行性疾病基础的各种类型的突变，并概述了一些可能有助于理清这些突变的策略。这些策略包括短重复序列的扩增、常见和低频遗传变异、新生突变、表观遗传变化、体细胞突变、上位性、寡基因和多基因假说。本文是名为“ALS复杂发病机制”的特刊的一部分。
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本文引用的文献
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Brain. 2014 Dec;137(Pt 12):e311. doi: 10.1093/brain/awu265. Epub 2014 Sep 26.
2
MAPT as a predisposing gene for sporadic amyotrophic lateral sclerosis in the Chinese Han population.MAPT 作为中国汉族散发性肌萎缩侧索硬化的易患基因。
Neural Regen Res. 2013 Nov 25;8(33):3116-23. doi: 10.3969/j.issn.1673-5374.2013.33.005.
3
Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy.一个常染色体显性遗传性线粒体肌病家族中新型核编码线粒体蛋白CHCHD10的突变
Neurogenetics. 2015 Jan;16(1):1-9. doi: 10.1007/s10048-014-0421-1. Epub 2014 Sep 6.
4
Screening of CHCHD10 in a French cohort confirms the involvement of this gene in frontotemporal dementia with amyotrophic lateral sclerosis patients.在一个法国队列中对CHCHD10进行筛查，证实了该基因与患有肌萎缩侧索硬化症的额颞叶痴呆患者有关。
Neurobiol Aging. 2014 Dec;35(12):2884.e1-2884.e4. doi: 10.1016/j.neurobiolaging.2014.07.022. Epub 2014 Jul 24.
5
Two novel mutations in conserved codons indicate that CHCHD10 is a gene associated with motor neuron disease.保守密码子中的两个新突变表明CHCHD10是一种与运动神经元疾病相关的基因。
Brain. 2014 Dec;137(Pt 12):e309. doi: 10.1093/brain/awu227. Epub 2014 Aug 11.
6
Genome-wide analysis of the heritability of amyotrophic lateral sclerosis.肌萎缩侧索硬化症遗传力的全基因组分析。
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7
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8
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Nat Neurosci. 2014 May;17(5):664-666. doi: 10.1038/nn.3688. Epub 2014 Mar 30.
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J Neurol Sci. 2014 May 15;340(1-2):63-8. doi: 10.1016/j.jns.2014.02.026. Epub 2014 Feb 28.
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