Variation of BMP3 contributes to dog breed skull diversity.

Cancer Genetics Branch, National Human Genome Research Institute, Bethesda, Maryland, United States of America.
PLoS Genetics (Impact Factor: 8.17). 08/2012; 8(8):e1002849. DOI: 10.1371/journal.pgen.1002849
Source: PubMed

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.

1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rapid advancement of next-generation sequencing technology has generated a deluge of genomic data from domesticated dogs and their wild ancestor, grey wolves, which have simultaneously broadened our understanding of domestication and diseases that are shared by humans and dogs. To address the scarcity of single nucleotide polymorphism (SNP) data provided by authorized databases and to make SNP data more easily/friendly usable and available, we propose DoGSD (, the first canidae-specific database which focuses on whole genome SNP data from domesticated dogs and grey wolves. The DoGSD is a web-based, open-access resource comprising ∼19 million high-quality whole-genome SNPs. In addition to the dbSNP data set (build 139), DoGSD incorporates a comprehensive collection of SNPs from two newly sequenced samples (1 wolf and 1 dog) and collected SNPs from three latest dog/wolf genetic studies (7 wolves and 68 dogs), which were taken together for analysis with the population genetic statistics, Fst. In addition, DoGSD integrates some closely related information including SNP annotation, summary lists of SNPs located in genes, synonymous and non-synonymous SNPs, sampling location and breed information. All these features make DoGSD a useful resource for in-depth analysis in dog-/wolf-related studies. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 11/2014; DOI:10.1093/nar/gku1174 · 8.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated patterns of evolutionary integration in the appendicular skeleton of mammalian carnivores. The findings are discussed in relation to performance selection in terms of organismal function as a potential mechanism underlying integration. Interspecific shape covariation was quantified by 2B-PLS analysis of 3D landmark data within a phylogenetic context. Specifically, we compared pairs of anatomically connected bones (within-limbs) and pairs of both serially homologous and functional equivalent bones (between-limbs). The statistical results of all the comparisons suggest that the carnivoran appendicular skeleton is highly integrated. Strikingly, the main shape covariation relates to bone robustness in all cases. A bootstrap test specifically developed to compare the degree of integration between specialized cursorial taxa (i.e., those whose forelimbs are primarily involved in locomotion) and non-cursorial species (i.e., those whose forelimbs are involved in more functions than their hind limb) showed that cursors have a more integrated appendicular skeleton than non-cursors. The findings demonstrate that natural selection can influence the pattern and degree of morphological integration by increasing the degree of bone shape covariation in parallel to ecological specialization.This article is protected by copyright. All rights reserved.
    Evolution 11/2014; 69(2):321-340. DOI:10.1111/evo.12566 · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interstitial deletions of 4q21 (MIM 613509) have already been reported in more than a dozen patients with deletions ranging from 2 to 15.1 Mb delineating a common phenotype including marked growth restriction, hypotonia, severe developmental delay with absent or delayed speech and distinctive facial features. A minimal critical region of 1.37 Mb accounting for the common features with 5 known genes (PRKG2, RASGEF1B, HNRNPD, HNRPDL, and ENOPH1) has been described so far. Here we report on a 5 year-old Hungarian girl presenting with severe developmental delay, good receptive language but absent spoken speech, short stature, dystrophy, hypotonia, distinctive facies including broad forehead, frontal bossing, downward slanting palpebral fissures, hypertelorism, hypoplastic ear-lobes, anteverted nostrils, short philtrum, small mouth, higharched palate, short, small hands and feet, distally narrowing fingers and clinodactyly. Cerebral MRI showed ventricular dilation and an increase in periventricular signal intensity. After extensive metabolic tests and exclusion of subtelomeric deletions array CGH analysis was performed using the Agilent Human Genome G3 SurePrint 8x60K Microarray (Agilent Technologies, USA), which detected a 4,85 Mb de novo interstitial deletion of 4q21.21-4q21.23. The clinical symptoms only partly overlap with reported 4q21 microdeletion cases. Among multiple annotated genes our patient is also haploinsufficient for the following genes: RASGEF1B being a strong candidate for the neurodevelopmental features and PRKG2 for severe growth delay. The first Hungarian case of 4q21 deletion adds to the phenotypic spectrum of this novel microdeletion syndrome and underlines the importance of array CGH to uncover the heterogeneous causes of intellectual disability.
    Molecular Cytogenetics 03/2015; 8:16. DOI:10.1186/s13039-015-0118-7 · 2.66 Impact Factor

Full-text (2 Sources)

Available from
May 21, 2014