The Evolving Genetic Risk for Sporadic ALS  

Oleh:

Gibson, Summer B. ; Downie, Jonathan M. ; Tsetsou, Spyridoula ; Feusier, Julie E. ; Figueroa, Karla P. ; Bromberg, Mark B. ; Jorde, Lynn B. ; Pulst, Stefan M.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Neurology (Official Journal of The American Academy of Neurology) vol. 89 no. 03 (Jul. 2017), page 226-233.
Topik: Sporadic ALS
Fulltext: N11 v89 n3 p226 kelik2017.pdf (514.04KB)

Ketersediaan

Perpustakaan FK Nomor Panggil: N11.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Objective: To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Methods: Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALSassociated genes in patients with SALS vs 324 normal controls. Results: Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Conclusions: Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali