@article{Gelfman02042019,
author = {Gelfman, Sahar and Dugger, Sarah A and Araujo Martins Moreno, Cristiane and Ren, Zhong and Wolock, Charles J and Shneider, Neil and Phatnani, Hemali and Cirulli, Elizabeth T and Lasseigne, Brittany N and Harris, Timothy and Maniatis, Tom and Rouleau, Guy and Brown, Robert H and Gitler, Aaron D and Myers, Richard M and Petrovski, Slave and Allen, Andrew and Goldstein, David B and Harms, Matthew B}, 
title = {A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS},
year = {2019}, 
doi = {10.1101/gr.243592.118}, 
elocation-id = {gr.243592.118}, 
abstract ={Large-scale sequencing efforts in amyotrophic lateral sclerosis (ALS) have implicated novel genes using gene-based collapsing methods. However, pathogenic mutations may be concentrated in specific genic regions. To address this, we developed two collapsing strategies, one focuses rare variation collapsing on homology-based protein domains as the unit for collapsing and another gene-level approach that, unlike standard methods, leverages existing evidence of purifying selection against missense variation on said domains. The application of these two collapsing methods to 3,093 ALS cases and 8,186 controls of European ancestry, and also 3,239 cases and 11,808 controls of diversified populations, pinpoints risk regions of ALS genes including SOD1, NEK1, TARDBP, and FUS. While not clearly implicating novel ALS genes, the new analyses not only pinpoint risk regions in known genes but also highlight candidate genes as well.}, 
URL = {http://genome.cshlp.org/content/early/2019/04/02/gr.243592.118.abstract}, 
eprint = {http://genome.cshlp.org/content/early/2019/04/02/gr.243592.118.full.pdf+html}, 
journal = {Genome Research} 
}