Journal article
Analysis of sequence data to identify potential risk variants for oral clefts in multiplex families
Molecular genetics & genomic medicine, Vol.5(5), pp.570-579
09/2017
DOI: 10.1002/mgg3.320
PMCID: PMC5606860
PMID: 28944239
Abstract
BackgroundNonsyndromic oral clefts are craniofacial malformations, which include cleft lip with or without cleft palate. The etiology for oral clefts is complex with both genetic and environmental factors contributing to risk. Previous genome-wide association (GWAS) studies have identified multiple loci with small effects; however, many causal variants remain elusive.
MethodsIn this study, we address this by specifically looking for rare, potentially damaging variants in family-based data. We analyzed both whole exome sequence (WES) data and whole genome sequence (WGS) data in multiplex cleft families to identify variants shared by affected individuals.
ResultsHere we present the results from these analyses. Our most interesting finding was from a single Syrian family, which showed enrichment of nonsynonymous and potentially damaging rare variants in two genes: CASP9 and FAT4.
ConclusionNeither of these candidate genes has previously been associated with oral clefts and, if confirmed as contributing to disease risk, may indicate novel biological pathways in the genetic etiology for oral clefts.
Details
- Title: Subtitle
- Analysis of sequence data to identify potential risk variants for oral clefts in multiplex families
- Creators
- Emily R. Holzinger - National Human Genome Research InstituteQing Li - National Human Genome Research InstituteMargaret M. Parker - Harvard UniversityJacqueline B. Hetmanski - Johns Hopkins UniversityMary L. Marazita - University of PittsburghElisabeth Mangold - University of BonnKerstin U. Ludwig - Life & BrainMargaret A. Taub - Johns Hopkins UniversityFerdouse Begum - Johns Hopkins UniversityJeffrey C. Murray - University of IowaHasan Albacha-Hejazi - Hejazi Clin, Damascus, SyriaKhalid Alqosayer - Prime Hlth Clin, Jeddah, Saudi ArabiaGiath Al-Souki - Saudi Red Crescent, Jeddah, Saudi ArabiaAbdullatiff Albasha Hejazi - Al Eqtisad Est, Jeddah, Saudi ArabiaAlan F. Scott - Johns Hopkins UniversityTerri H. Beaty - Johns Hopkins UniversityJoan E. Bailey-Wilson - National Human Genome Research Institute
- Resource Type
- Journal article
- Publication Details
- Molecular genetics & genomic medicine, Vol.5(5), pp.570-579
- DOI
- 10.1002/mgg3.320
- PMID
- 28944239
- PMCID
- PMC5606860
- NLM abbreviation
- Mol Genet Genomic Med
- ISSN
- 2324-9269
- eISSN
- 2324-9269
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- P50-DE-016215; R01-DE-009886; R01-DE-014581; R01-DE-016148; R37-DE-08559; U01-DE-018993; U01-DE-020073; X01 HG006177; HHSN268200782096C / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985035878302771
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