title: Variation of BMP3 contributes to dog breed skull diversity.
abstract: Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
authors.affiliation: Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Schoenebeck
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Hutchinson
authors.forename: Alexandra
authors.initials: A
authors.lastname: Byers
authors.forename: Holly C
authors.initials: HC
authors.lastname: Beale
authors.forename: Blake
authors.initials: B
authors.lastname: Carrington
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Faden
authors.forename: Maud
authors.initials: M
authors.lastname: Rimbault
authors.forename: Brennan
authors.initials: B
authors.lastname: Decker
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Kidd
authors.forename: Raman
authors.initials: R
authors.lastname: Sood
authors.forename: Adam R
authors.initials: AR
authors.lastname: Boyko
authors.forename: John W
authors.initials: JW
authors.lastname: Fondon
authors.forename: Robert K
authors.initials: RK
authors.lastname: Wayne
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Bustamante
authors.forename: Brian
authors.initials: B
authors.lastname: Ciruna
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
mesh_terms: D000818:Animals; D005075:Biological Evolution; D055398:Bone Morphogenetic Protein 3 / Q000235:genetics*; D001947:Breeding; D002874:Chromosome Mapping; D003398:Craniosynostoses / Q000235:genetics*; D004285:Dogs / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense; D057805:Pets; D010641:Phenotype; D040641:Quantitative Trait Loci; D012886:Skull / Q000033:anatomy & histology / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics
chemical_list: D055398:Bone Morphogenetic Protein 3