Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

Nature communications (2019-09-14)
Robert Fragoza, Jishnu Das, Shayne D Wierbowski, Jin Liang, Tina N Tran, Siqi Liang, Juan F Beltran, Christen A Rivera-Erick, Kaixiong Ye, Ting-Yi Wang, Li Yao, Matthew Mort, Peter D Stenson, David N Cooper, Xiaomu Wei, Alon Keinan, John C Schimenti, Andrew G Clark, Haiyuan Yu

Each human genome carries tens of thousands of coding variants. The extent to which this variation is functional and the mechanisms by which they exert their influence remains largely unexplored. To address this gap, we leverage the ExAC database of 60,706 human exomes to investigate experimentally the impact of 2009 missense single nucleotide variants (SNVs) across 2185 protein-protein interactions, generating interaction profiles for 4797 SNV-interaction pairs, of which 421 SNVs segregate at > 1% allele frequency in human populations. We find that interaction-disruptive SNVs are prevalent at both rare and common allele frequencies. Furthermore, these results suggest that 10.5% of missense variants carried per individual are disruptive, a higher proportion than previously reported; this indicates that each individual's genetic makeup may be significantly more complex than expected. Finally, we demonstrate that candidate disease-associated mutations can be identified through shared interaction perturbations between variants of interest and known disease mutations.

Referencia del producto
Descripción del producto

Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Ammonium molybdate, 99.98% trace metals basis
Monoclonal Anti-HA antibody produced in mouse, clone HA-7, purified from hybridoma cell culture
Malachite Green chloride, analytical standard
Anti-γ-Tubulin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution

Redes sociales

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon


Investigación. Desarrollo. Producción.

Somos un proveedor líder para la industria de Ciencias de la Vida con soluciones y servicios para investigación, desarrollo y producción biotecnológicos, y para desarrollo y producción de tratamientos farmacéuticos

© 2021 Merck KGaA, Darmstadt, Alemania y/o sus filiales. Todos los derechos reservados.

Queda estrictamente prohibida la reproducción sin permiso de cualquiera de los materiales de la página web.