3 documents found, page 1 of 1
Structural variation analysis of 6,500 whole genome sequences in amyotrophic la...
Al Khleifat, Ahmad; Iacoangeli, Alfredo; van Vugt, Joke J. F. A.; Bowles, Harry; Moisse, Matthieu; Zwamborn, Ramona A. J.; van der Spek, Rick A. A.There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated associati...
Genome-wide analyses identify KIF5A as a novel ALS gene
Nicolas, Aude; Kenna, Kevin P.; Renton, Alan E.; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A.; Kenna, Brendan J.; Nalls, Mike A.To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Int...
Targeted genetic screen in Amyotrophic lateral sclerosis reveals novel genetic ...
Cooper-Knock, Johnathan; Robins, Henry; Niedermoser, Isabell; Wyles, Matthew; Heath, Paul R.; Higginbottom, Adrian; Walsh, Theresa; Kazoka, MbombeAmyotrophic lateral sclerosis (ALS) is underpinned by an oligogenic rare variant architecture. Identified genetic variants of ALS include RNA-binding proteins containing prion-like domains (PrLDs). We hypothesized that screening genes encoding additional similar proteins will yield novel genetic causes of ALS. The most common genetic variant of ALS patients is a G4C2-repeat expansion within C9ORF72. We have sho...