Author:
Bishop Madison R.,Perez Kimberly Diaz,Sun Miranda,Ho Samantha,Chopra Pankaj,Mukhopadhyay Nandita,Hetmanski Jacqueline B.,Taub Margaret A.,Moreno-Uribe Lina M.,Valencia-Ramirez Luz Consuelo,Restrepo Muñeton Claudia P.,Wehby George,Hecht Jacqueline T.,Deleyiannis Frederic,Weinberg Seth M.,Wu-Chou Yah Huei,Chen Philip K.,Brand Harrison,Epstein Michael P.,Ruczinski Ingo,Murray Jeffrey C.,Beaty Terri H.,Feingold Eleanor,Lipinski Robert J.,Cutler David J.,Marazita Mary L.,Leslie Elizabeth J.
Abstract
AbstractWhile de novo mutations (DNMs) are known to increase risk of congenital defects, DNMs have not been fully explored regarding orofacial clefts (OFCs), one of the most common human birth defects. Therefore, whole-genome sequencing of 756 case-parent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to OFC risk. Overall, we identified a significant excess of loss-of-function DNMs in genes highly expressed in craniofacial tissues, as well as genes associated with known autosomal dominant OFC syndromes. This analysis also revealed roles for zinc-finger homeobox domain and SOX2-interacting genes in OFC etiology.
Publisher
Cold Spring Harbor Laboratory