Journal article
Whole exome association of rare deletions in multiplex oral cleft families
Genetic epidemiology, Vol.41(1), pp.61-69
01/2017
DOI: 10.1002/gepi.22010
PMCID: PMC5154821
PMID: 27910131
Abstract
By sequencing the exomes of distantly related individuals in multiplex families, rare mutational and structural changes to coding DNA can be characterized and their relationship to disease risk can be assessed. Recently, several rare single nucleotide variants (SNVs) were associated with an increased risk of nonsyndromic oral cleft, highlighting the importance of rare sequence variants in oral clefts and illustrating the strength of family-based study designs. However, the extent to which rare deletions in coding regions of the genome occur and contribute to risk of nonsyndromic clefts is not well understood. To identify putative structural variants underlying risk, we developed a pipeline for rare hemizygous deletions in families from whole exome sequencing and statistical inference based on rare variant sharing. Among 56 multiplex families with 115 individuals, we identified 53 regions with one or more rare hemizygous deletions. We found 45 of the 53 regions contained rare deletions occurring in only one family member. Members of the same family shared a rare deletion in only eight regions. We also devised a scalable global test for enrichment of shared rare deletions.
Details
- Title: Subtitle
- Whole exome association of rare deletions in multiplex oral cleft families
- Creators
- Jack Fu - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USATerri H Beaty - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USAAlan F Scott - Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore MD, USAJacqueline Hetmanski - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USAMargaret M Parker - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USAJoan E Bailey Wilson - Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD, USAMary L Marazita - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, PA, USAElisabeth Mangold - Institute of Human Genetics, University of Bonn, Bonn, GermanyHasan Albacha-Hejazi - Dr. Hejazi Clinic, Damascus, Syrian Arab RepublicJeffrey C Murray - Department of Pediatrics, School of Medicine, University of Iowa, IA, USAAlexandre Bureau - Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec and Département de Médecine Sociale et Préventive, Université Laval, Québec, CanadaJacob Carey - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USAStephen Cristiano - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USAIngo Ruczinski - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USARobert B Scharpf - Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.41(1), pp.61-69
- DOI
- 10.1002/gepi.22010
- PMID
- 27910131
- PMCID
- PMC5154821
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- United States
- Grant note
- R03 DE021437 / NIDCR NIH HHS P50 DE016215 / NIDCR NIH HHS R01 DE014581 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS HHSN268200782096C / NHLBI NIH HHS R03 DE025279 / NIDCR NIH HHS U01 DE018993 / NIDCR NIH HHS
- Language
- English
- Date published
- 01/2017
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025337802771
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