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PMID: 25316630 Published · ppublish English Journal Article Review

Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges.

Brain research ·Vol. 1607 ·2015-05-14 ·Pages 75-93

Marangi G, Traynor BJ

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.

Keywords
Amyotrophic lateral sclerosis GWAS Gene discovery Genetic heterogeneity NGS Somatic mosaicism
MeSH Terms
Amyotrophic Lateral Sclerosis/genetics Genetic Predisposition to Disease Genetic Techniques Humans Mutation
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Marangi Giuseppe
Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA; Institute of Medical Genetics, Catholic University, Roma, Italy. Electronic address: [email protected].
Traynor Bryan J
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.
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Article Info
Journal
Brain research
Abbr.
Brain Res
ISSN
1872-6240
DOI
10.1016/j.brainres.2014.10.009
Email
[email protected]
Published
2015-05-14
Epub
2014-00-12
Pages
75-93
Language
English
Region
Netherlands
NLM ID
0045503
PMCID
PMC5916786
Subset
IM
Grants
Intramural NIH HHS · ZIA AG000933-03 · United States
External Links
PubMed source DOI: 10.1016/j.brainres.2014.10.009 PMC Full Text View journal details
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