@article{Gelfman01052019,
author = {Gelfman, Sahar and Dugger, Sarah and de Araujo Martins Moreno, Cristiane and Ren, Zhong and Wolock, Charles J. and Shneider, Neil A. and Phatnani, Hemali and Cirulli, Elizabeth T. and Lasseigne, Brittany N. and Harris, Tim and Maniatis, Tom and Rouleau, Guy A. and Brown, Robert H. and Gitler, Aaron D. and Myers, Richard M. and Petrovski, Slavé 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},
volume = {29}, 
number = {5}, 
pages = {809-818}, 
year = {2019}, 
doi = {10.1101/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 the other is a 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 3093 ALS cases and 8186 controls of European ancestry, and also 3239 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/29/5/809.abstract}, 
eprint = {http://genome.cshlp.org/content/29/5/809.full.pdf+html}, 
journal = {Genome Research} 
}