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 - Funding Information:
These studies are part of the Gabriella Miller Kids First Pediatric Research Program Consortium, supported by the Common Fund of the Office of the Director of the National Institutes of Health (NIH). Sequencing of the European trios was completed at Washington University’s McDonnell Genome Institute ( 3U54HG003079-12S1 and X01-HL132363 [M.L.M. and E.F.]), and the Colombian and Taiwanese trios were sequenced at the Broad Institute Sequencing Center ( U24-HD090743 , X01-HL136465 [M.L.M. and E.F.], and X01-HL140516 [T.H.B. and Azeez Butali]). The sequencing centers plus the Kids First Data Resource Center, supported by the NIH Common Fund through grant U2CHL138346 , provided technical and analytical support of this project. The assembling of the sample of child-parent trios, collection of the phenotypic data and samples, and data analysis were supported by the additional grants from the NIH ( R01-DE016148 [M.L.M. and S.M.W.], R03-DE026469 [E.F. and M.L.M.], R03-DE027193 [E.J.L.], R00-DE025060 [E.J.L.], R01-DE011931 [J.T.H.], U01-DD000295 [G.W.], and R03-DE027121 [M.A.T., T.H.B., and J.B.]). This study would not be possible without the dedication of many families, study teams, and colleagues worldwide.
Funding Information:
These studies are part of the Gabriella Miller Kids First Pediatric Research Program Consortium, supported by the Common Fund of the Office of the Director of the National Institutes of Health (NIH). Sequencing of the European trios was completed at Washington University's McDonnell Genome Institute (3U54HG003079-12S1 and X01-HL132363 [M.L.M. and E.F.]), and the Colombian and Taiwanese trios were sequenced at the Broad Institute Sequencing Center (U24-HD090743, X01-HL136465 [M.L.M. and E.F.], and X01-HL140516 [T.H.B. and Azeez Butali]). The sequencing centers plus the Kids First Data Resource Center, supported by the NIH Common Fund through grant U2CHL138346, provided technical and analytical support of this project. The assembling of the sample of child-parent trios, collection of the phenotypic data and samples, and data analysis were supported by the additional grants from the NIH (R01-DE016148 [M.L.M. and S.M.W.], R03-DE026469 [E.F. and M.L.M.], R03-DE027193 [E.J.L.], R00-DE025060 [E.J.L.], R01-DE011931 [J.T.H.], U01-DD000295 [G.W.], and R03-DE027121 [M.A.T. T.H.B. and J.B.]). This study would not be possible without the dedication of many families, study teams, and colleagues worldwide.
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 - http://www.scopus.com/inward/record.url?scp=85087041727&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087041727&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2020.05.018
DO - 10.1016/j.ajhg.2020.05.018
M3 - Article
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 -