publication . Other literature type . Article . 2015

Massively Parallel Functional Analysis of BRCA1 RING Domain Variants

Muhtadi M. Islam; Justin Gullingsrud; Lea M. Starita; Stanley Fields; Jacob O. Kitzman; Jeffrey D. Parvin; Jay Shendure; Ronald J. Hause; David L. Young; Douglas M. Fowler;
Open Access English
  • Published: 30 Mar 2015
  • Publisher: Genetics Society of America
Abstract
Interpreting variants of uncertain significance (VUS) is a central challenge in medical genetics. One approach is to experimentally measure the functional consequences of VUS, but to date this approach has been post hoc and low throughput. Here we use massively parallel assays to measure the effects of nearly 2000 missense substitutions in the RING domain of BRCA1 on its E3 ubiquitin ligase activity and its binding to the BARD1 RING domain. From the resulting scores, we generate a model to predict the capacities of full-length BRCA1 variants to support homology-directed DNA repair, the essential role of BRCA1 in tumor suppression, and show that it outperforms wi...
Subjects
free text keywords: Corrigendum, Communications, Genomics, Biology, Genetics, Functional analysis, Massively parallel, Ubiquitin ligase, biology.protein, Mutation, medicine.disease_cause, medicine, BARD1, Missense mutation, DNA repair
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Europe PubMed Central
Other literature type . 2017
Europe PubMed Central
Other literature type . 2015
Genetics
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