|
|
|
|
Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate
|
|
|
|
|
|
|
|
نویسنده
|
wolf z.t. ,brand h.a. ,shaffer j.r. ,leslie e.j. ,arzi b. ,willet c.e. ,cox t.c. ,mchenry t. ,narayan n. ,feingold e. ,wang x. ,sliskovic s. ,karmi n. ,safra n. ,sanchez c. ,deleyiannis f.w.b. ,murray j.c. ,wade c.m. ,marazita m.l. ,bannasch d.l.
|
|
منبع
|
plos genetics - 2015 - دوره : 11 - شماره : 3
|
|
چکیده
|
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. © 2015 wolf et al.
|
|
|
|
|
آدرس
|
department of population health and reproduction,school of veterinary medicine university of california,davis,davis,ca, United States, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa,united states,department of human genetics,university of pittsburgh graduate school of public health,pittsburgh,pa,united states,molecular neurogenetics unit,psychiatric and neurodevelopmental genetics unit,center for human genetic research,massachusetts general hospital,boston,ma, United States, department of human genetics,university of pittsburgh graduate school of public health,pittsburgh,pa, United States, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa, United States, department of surgical and radiological sciences,school of veterinary medicine,university of california,davis,davis,ca, United States, university of sydney,sydney,nsw, Australia, department of pediatrics (division of craniofacial medicine),university of washington,seattle,wa,united states,center for developmental biology and regenerative medicine,seattle children’s research institute,seattle,wa,united states,department of anatomy & developmental biology,monash university,clayton,vic, Australia, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa, United States, department of medical microbiology and immunology,school of medicine,university of california,davis,davis,ca, United States, department of human genetics,university of pittsburgh graduate school of public health,pittsburgh,pa, United States, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa,united states,glaxosmithkline,research triangle park,nc, United States, department of population health and reproduction,school of veterinary medicine university of california,davis,davis,ca, United States, department of population health and reproduction,school of veterinary medicine university of california,davis,davis,ca, United States, department of population health and reproduction,school of veterinary medicine university of california,davis,davis,ca, United States, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa, United States, department of surgery,plastic and reconstructive surgery,university of colorado school of medicine,aurora,co, United States, division of neonatology,department of pediatrics,university of iowa,iowa city,ia, United States, university of sydney,sydney,nsw, Australia, center for craniofacial and dental genetics,department of oral biology,university of pittsburgh school of dental medicine,pittsburgh,pa,united states,clinical and translational science and department of psychiatry,university of pittsburgh school of medicine,pittsburgh,pa, United States, department of population health and reproduction,school of veterinary medicine university of california,davis,davis,ca, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|