TY - JOUR
T1 - Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios
AU - Bishop, Madison R.
AU - Diaz Perez, Kimberly K.
AU - Sun, Miranda
AU - Ho, Samantha
AU - Chopra, Pankaj
AU - Mukhopadhyay, Nandita
AU - Hetmanski, Jacqueline B.
AU - Taub, Margaret A.
AU - Moreno-Uribe, Lina M.
AU - Valencia-Ramirez, Luz Consuelo
AU - Restrepo Muñeton, Claudia P.
AU - Wehby, George
AU - Hecht, Jacqueline T.
AU - Deleyiannis, Frederic
AU - Weinberg, Seth M.
AU - Wu-Chou, Yah Huei
AU - Chen, Philip K.
AU - Brand, Harrison
AU - Epstein, Michael P.
AU - Ruczinski, Ingo
AU - Murray, Jeffrey C.
AU - Beaty, Terri H.
AU - Feingold, Eleanor
AU - Lipinski, Robert J.
AU - Cutler, David J.
AU - Marazita, Mary L.
AU - Leslie, Elizabeth J.
N1 - Publisher Copyright:
© 2020 American Society of Human Genetics
PY - 2020/7/2
Y1 - 2020/7/2
N2 - Although de novo mutations (DNMs) are known to increase an individual's 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 child-parent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to an individual's 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.
AB - Although de novo mutations (DNMs) are known to increase an individual's 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 child-parent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to an individual's 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.
KW - de novo mutations
KW - orofacial clefts
KW - trios
KW - whole genome sequencing
UR - https://www.scopus.com/pages/publications/85087041727
U2 - 10.1016/j.ajhg.2020.05.018
DO - 10.1016/j.ajhg.2020.05.018
M3 - 文章
C2 - 32574564
AN - SCOPUS:85087041727
SN - 0002-9297
VL - 107
SP - 124
EP - 136
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -