Molecular Deconvolution Platform to Establish Disease Mechanisms by Surveying GPCR Signaling.

ABSTRACT: Despite the wealth of genetic information available, mechanisms underlying pathological effects of disease-associated mutations in components of G protein-coupled receptor (GPCR) signaling cascades remain elusive. In this study, we developed a scalable approach for the functional analysis of clinical variants in GPCR pathways along with a complete analytical framework. We applied the strategy to evaluate an extensive set of dystonia-causing mutations in G protein Gαolf. Our quantitative analysis revealed diverse mechanisms by which pathogenic variants disrupt GPCR signaling, leading to a mechanism-based classification of dystonia. In light of significant clinical heterogeneity, the mechanistic analysis of individual disease-associated variants permits tailoring personalized intervention st

SUBMITTER: Masuho I 

PROVIDER: S-EPMC6077248 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature