Whole-genome association studies of sporadic amyotrophic lateral sclerosis: are retroelements involved?
Whole-genome association studies (WGASs) have identified single-nucleotide polymorphisms (SNPs) associated with sporadic amyotrophic lateral sclerosis (sALS). However, WGASs have so far produced results that are not consistent with those obtained from monogenic association studies focused on genes found to be relevant to ALS in functional biological studies. We propose that such inconsistencies might be at least partially alleviated by using approaches that integrate weakly associated SNPs. Several independent studies have detected abnormal reverse transcriptase (RT) activity in sALS patients, suggesting the involvement of retroelements in ALS pathogenesis. Here, we discuss the functions of genes with SNPs or mutations in sALS and consider whether these might implicate the involvement of a putative retroelement associated with sALS pathogenesis. New experimental models for studying retroviral activation and the effects of xenobiotic agents in ALS will be needed to further investigate a potential role of retroelements in the etiology of sALS.
Mougeot
Jean-Luc
JL
Department of Neurology, Carolinas Medical Center/ALS Research Laboratory, Cannon Research Center-R401, 1542 Garden Terrace, Charlotte, NC 28203, USA. jean-luc.mougeot@carolinas.org
Richardson-Milazi
Stephanie
S
Brooks
Benjamin Rix
BR