Dataset
Data from: Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate
Dryad
02/27/2016
DOI: 10.5061/dryad.j8r8q
Abstract
Cleft lip with or without cleft palate (CL/P) is the most commonly
occurring craniofacial birth defect. We provide insight into the genetic
etiology of this birth defect by performing genome-wide association
studies in two species: dogs and humans. In the dog, a genome-wide
association study of 7 CL/P cases and 112 controls from the Nova Scotia
Duck Tolling Retriever (NSDTR) breed identified a significantly associated
region on canine chromosome 27 (unadjusted p=1.1 x 10-13; adjusted p= 2.2
x 10-3). Further analysis in NSDTR families and additional full sibling
cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 –
10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft
palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3
CLPS cases and 4 controls at 15X coverage led to the discovery of a
frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)),
which segregated concordant with the phenotype. In a parallel study in
humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420
unaffected relatives, and 392 controls from a Guatemalan cohort,
identified a suggestive association (rs10785430; p =2.67 x 10-6) with the
same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was
unable to identify a causative mutation within the coding region of
ADAMTS20, but four coding variants were found in additional cases of CL/P.
In summary, this study provides genetic evidence for a role of ADAMTS20 in
CL/P development in dogs and as a candidate gene for CL/P development in
humans.
Details
- Title: Subtitle
- Data from: Genome-wide association studies in dogs and humans identify ADAMTS20 as a risk variant for cleft lip and palate
- Creators
- Zena T. Wolf - University of California, DavisHarrison A. Brand - University of PittsburghJohn R. Shaffer - University of PittsburghElizabeth J. Leslie - University of PittsburghBoaz Arzi - University of California, DavisCali E. Willet - The University of SydneyTimothy C. Cox - University of WashingtonToby McHenry - University of PittsburghNicole Narayan - University of California, DavisEleanor Feingold - University of PittsburghXioajing Wang - University of PittsburghSaundra Sliskovic - University of California, DavisNili Karmi - University of California, DavisNoa Safra - University of California, DavisCarla Sanchez - University of PittsburghFrederic W. B. DeleyiannisJeffrey C. Murray - University of IowaClaire M. Wade - The University of SydneyMary L. Marazita - University of PittsburghDanika L. Bannasch - University of California, Davis
- Resource Type
- Dataset
- DOI
- 10.5061/dryad.j8r8q
- Publisher
- Dryad
- Language
- English
- Date published
- 02/27/2016
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985075321802771
Metrics
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