Analysis of sequence data to identify potential risk variants for oral clefts in multiplex families
Year: 2017
Type: article
Study design: Observational Study
Abstract: Background Nonsyndromic 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. Methods In 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. Results Here 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. Conclusion Neither 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.
DOI: 10.1002/mgg3.320
Authors: Emily R. Holzinger, Qing Li, Margaret M. Parker, Jacqueline B. Hetmanski, Mary L. Marazita, Elisabeth Mangold, Kerstin U. Ludwig, Margaret A. Taub, Ferdouse Begum, Jeffrey C. Murray, Hasan Albacha-Hejazi, Khalid Alqosayer, Giath Al-Souki, Abdullatiff Albasha Hejazi, Alan F. Scott, Terri H. Beaty, Joan E. Bailey-Wilson
Institutions: National Institutes of Health, National Human Genome Research Institute, National Institute of General Medical Sciences, Brigham and Women's Hospital, Harvard University, Johns Hopkins University, University of Pittsburgh, University of Bonn, University of Iowa, Hafez Hospital, Johns Hopkins Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,900
Awards: G2146332128, GENE MAPPING STUDIES OF ORAL/FACIAL CLEFTS--CHINA/INDIA, G2509796369, International Consortium to Identify Genes and Interactions Controlling Oral Clef, Extending the Phenotype of Nonsyndromic Orofacial Clefting, G3715026652, Oral Clefts: Moving from Genome Wide Studies Toward Functional Genomics, G7093047072, International Genetic Epidemiology of Oral Clefts, G8267674335, G9000076949, G9000160421
OpenAlex ID: W2743567608