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A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS.

Publication ,  Journal Article
Gelfman, S; Dugger, S; de Araujo Martins Moreno, C; Ren, Z; Wolock, CJ; Shneider, NA; Phatnani, H; Cirulli, ET; Lasseigne, BN; Harris, T ...
Published in: Genome Res
May 2019

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.

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

May 2019

Volume

29

Issue

5

Start / End Page

809 / 818

Location

United States

Related Subject Headings

  • White People
  • Superoxide Dismutase-1
  • Risk Factors
  • RNA-Binding Protein FUS
  • Protein Domains
  • NIMA-Related Kinase 1
  • Mutation
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
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Gelfman, S., Dugger, S., de Araujo Martins Moreno, C., Ren, Z., Wolock, C. J., Shneider, N. A., … Harms, M. B. (2019). A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS. Genome Res, 29(5), 809–818. https://doi.org/10.1101/gr.243592.118
Gelfman, Sahar, Sarah Dugger, Cristiane de Araujo Martins Moreno, Zhong Ren, Charles J. Wolock, Neil A. Shneider, Hemali Phatnani, et al. “A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS.Genome Res 29, no. 5 (May 2019): 809–18. https://doi.org/10.1101/gr.243592.118.
Gelfman S, Dugger S, de Araujo Martins Moreno C, Ren Z, Wolock CJ, Shneider NA, et al. A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS. Genome Res. 2019 May;29(5):809–18.
Gelfman, Sahar, et al. “A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS.Genome Res, vol. 29, no. 5, May 2019, pp. 809–18. Pubmed, doi:10.1101/gr.243592.118.
Gelfman S, Dugger S, de Araujo Martins Moreno C, Ren Z, Wolock CJ, Shneider NA, Phatnani H, Cirulli ET, Lasseigne BN, Harris T, Maniatis T, Rouleau GA, Brown RH, Gitler AD, Myers RM, Petrovski S, Allen A, Goldstein DB, Harms MB. A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS. Genome Res. 2019 May;29(5):809–818.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

May 2019

Volume

29

Issue

5

Start / End Page

809 / 818

Location

United States

Related Subject Headings

  • White People
  • Superoxide Dismutase-1
  • Risk Factors
  • RNA-Binding Protein FUS
  • Protein Domains
  • NIMA-Related Kinase 1
  • Mutation
  • Male
  • Humans
  • Genome-Wide Association Study