Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.
candidate gene
congenital birth defect
craniofacial genetics
genome-wide association studies
novel variants
whole-exome sequencing
Journal
Oral diseases
ISSN: 1601-0825
Titre abrégé: Oral Dis
Pays: Denmark
ID NLM: 9508565
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
revised:
14
04
2021
received:
31
12
2020
accepted:
09
05
2021
pubmed:
2
6
2021
medline:
15
9
2022
entrez:
1
6
2021
Statut:
ppublish
Résumé
Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.
Identifiants
pubmed: 34061439
doi: 10.1111/odi.13932
pmc: PMC9733635
mid: NIHMS1710679
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
GDF11 protein, human
0
Growth Differentiation Factors
0
Types de publication
Journal Article
Langues
eng
Pagination
1921-1935Subventions
Organisme : NIDCR NIH HHS
ID : R01DE028300
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM133807
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD007587
Pays : United States
Organisme : NIDCR NIH HHS
ID : R00 DE024571
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE028300
Pays : United States
Organisme : NIDCR NIH HHS
ID : R03 DE024776
Pays : United States
Organisme : NIDCR NIH HHS
ID : R00 DE022378
Pays : United States
Organisme : NIDCR NIH HHS
ID : R90 DE024296
Pays : United States
Organisme : NIMHD NIH HHS
ID : S21 MD001830
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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