Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Madison R. Bishop; Kimberly K. Diaz Perez; Miranda Sun; Samantha Ho; Pankaj Chopra; Nandita Mukhopadhyay; Jacqueline B. Hetmanski; Margaret A. Taub; Lina M. Moreno-Uribe; Luz Consuelo Valencia-Ramirez; Claudia P. Restrepo Muñeton; George Wehby; Jacqueline T. Hecht; Frederic Deleyiannis; Seth M. Weinberg; Yah Huei Wu-Chou; Philip K. Chen; Harrison Brand; Michael P. Epstein; Ingo Ruczinski; Jeffrey C. Murray; Terri H. Beaty; Eleanor Feingold; Robert J. Lipinski; David J. Cutler; Mary L. Marazita; Elizabeth J. Leslie

doi:10.1016/j.ajhg.2020.05.018

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Madison R. Bishop
, Kimberly K. Diaz Perez
, Miranda Sun
, Samantha Ho
, Pankaj Chopra
, Nandita Mukhopadhyay
, Jacqueline B. Hetmanski
, Margaret A. Taub
, Lina M. Moreno-Uribe
, Luz Consuelo Valencia-Ramirez
, Claudia P. Restrepo Muñeton
, George Wehby
, Jacqueline T. Hecht
, Frederic Deleyiannis
, Seth M. Weinberg
, Yah Huei Wu-Chou
, Philip K. Chen
, Harrison Brand
, Michael P. Epstein
, Ingo Ruczinski

Jeffrey C. Murray, Terri H. Beaty, Eleanor Feingold, Robert J. Lipinski, David J. Cutler, Mary L. Marazita, Elizabeth J. Leslie^*

^*Corresponding author for this work

Emory University
University of Wisconsin-Madison
University of Pittsburgh
Johns Hopkins University
University of Iowa
Fundación Clínica Noel
University of Texas Health Science Center at Houston
UCHealth Plastic and Reconstructive Surgery
Chang Gung Memorial Hospital
Taipei Medical University
Massachusetts General Hospital

Research output: Contribution to journal › Journal Article › peer-review

66 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	124-136
Number of pages	13
Journal	American Journal of Human Genetics
Volume	107
Issue number	1
DOIs	https://doi.org/10.1016/j.ajhg.2020.05.018
State	Published - 02 07 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 American Society of Human Genetics

Keywords

de novo mutations
orofacial clefts
trios
whole genome sequencing

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10.1016/j.ajhg.2020.05.018

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Bishop, M. R., Diaz Perez, K. K., Sun, M., Ho, S., Chopra, P., Mukhopadhyay, N., Hetmanski, J. B., Taub, M. A., Moreno-Uribe, L. M., Valencia-Ramirez, L. C., Restrepo Muñeton, C. P., Wehby, G., Hecht, J. T., Deleyiannis, F., Weinberg, S. M., Wu-Chou, Y. H., Chen, P. K., Brand, H., Epstein, M. P., ... Leslie, E. J. (2020). Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios. American Journal of Human Genetics, 107(1), 124-136. https://doi.org/10.1016/j.ajhg.2020.05.018

@article{24d6d443cd244a6f96474c76e7cdc4af,

title = "Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios",

abstract = "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.",

keywords = "de novo mutations, orofacial clefts, trios, whole genome sequencing",

author = "Bishop, \{Madison R.\} and \{Diaz Perez\}, \{Kimberly K.\} and Miranda Sun and Samantha Ho and Pankaj Chopra and Nandita Mukhopadhyay and Hetmanski, \{Jacqueline B.\} and Taub, \{Margaret A.\} and Moreno-Uribe, \{Lina M.\} and Valencia-Ramirez, \{Luz Consuelo\} and \{Restrepo Mu{\~n}eton\}, \{Claudia P.\} and George Wehby and Hecht, \{Jacqueline T.\} and Frederic Deleyiannis and Weinberg, \{Seth M.\} and Wu-Chou, \{Yah Huei\} and Chen, \{Philip K.\} and Harrison Brand and Epstein, \{Michael P.\} and Ingo Ruczinski and Murray, \{Jeffrey C.\} and Beaty, \{Terri H.\} and Eleanor Feingold and Lipinski, \{Robert J.\} and Cutler, \{David J.\} and Marazita, \{Mary L.\} and Leslie, \{Elizabeth J.\}",

note = "Publisher Copyright: {\textcopyright} 2020 American Society of Human Genetics",

year = "2020",

month = jul,

day = "2",

doi = "10.1016/j.ajhg.2020.05.018",

language = "英语",

volume = "107",

pages = "124--136",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

}

Bishop, MR, Diaz Perez, KK, Sun, M, Ho, S, Chopra, P, Mukhopadhyay, N, Hetmanski, JB, Taub, MA, Moreno-Uribe, LM, Valencia-Ramirez, LC, Restrepo Muñeton, CP, Wehby, G, Hecht, JT, Deleyiannis, F, Weinberg, SM, Wu-Chou, YH, Chen, PK, Brand, H, Epstein, MP, Ruczinski, I, Murray, JC, Beaty, TH, Feingold, E, Lipinski, RJ, Cutler, DJ, Marazita, ML & Leslie, EJ 2020, 'Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios', American Journal of Human Genetics, vol. 107, no. 1, pp. 124-136. https://doi.org/10.1016/j.ajhg.2020.05.018

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.

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 -

Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Abstract

Bibliographical note

Keywords

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