Best variants associated with SBW above 41 kg in dogs, identified on the locus 1 (CFAX) using 163 WGS data.

<p>Best variants associated with SBW above 41 kg in dogs, identified on the locus 1 (CFAX) using 163 WGS data.</p

Distribution of the derived <i>ACSL4</i> allele in the large dog breeds.

<p>The Bullmastiff, Dogue de Bordeaux, English Mastiff, Greater Swiss Mountain Dog, Newfoundland, Rottweiler and the Saint Bernard are homozygous for the derived allele (red) while Bernese Mountain Dog, Black Russian Terrier, Dogo/Presa Canario, Kuvasz and Leonberger were either homozygous or heterozygous (yellow) at <i>ACSL4</i>. Other large dog breeds (<i>e</i>.<i>g</i>. Akita, Anatolian Shepherd Dog, Cane Corso, Great Dane, Great Pyrenees, Irish Wolfhound, Neapolitan Mastiff, Otterhound, Scottish Deerhound, Tibetan Mastiff, Tosa Inu), wild canids and all medium/small breeds carry the ancestral allele in the homozygous state (blue). Pictures provide by the American Kennel Club (AKC) and Larousse.</p

GWAS results for 165 large breed dogs <i>vs</i>. 690 medium/small breed dogs.

<p>(A) Manhattan plot for the GWAS is shown. The -log₁₀ P-values for each SNP are plotted on the y-axis <i>versus</i> each canine autosome and the X chromosome on the x-axis. The red line represents the Bonferroni corrected significance threshold (-log₁₀ (P) = 6.48) and SNPs passing this threshold are colored in red. (B and C) Regional plot for genome-wide significant association on the X chromosome for 78–86 Mb (B) and 98–106 Mb (C). Each plot spans the genomic regions from 4000 kb upstream to 4000 kb downstream of the most significant SNP at each locus. SNPs are colored based on the strength of LD values (r² values) considering the most strongly associated SNP and the other SNPs in the region.</p

Conservation of <i>IRS4</i> mutated codons (in bold) between mammals.

<p>Conservation of <i>IRS4</i> mutated codons (in bold) between mammals.</p

Conservation of <i>IGSF1</i> mutated codons (in bold) between mammals.

<p>Conservation of <i>IGSF1</i> mutated codons (in bold) between mammals.</p

Derived allele frequencies at multiple loci involved in body weight and size variations in (A) modern dog breeds, (B) modern dog breeds without inclusion of muscled breeds, (C) only muscled breeds.

<p>The frequency of the derived allele in 5-kg weigh classes is represented on a color scale. Dogs with a SBW above 65 kg are collapsed in a single category (>65 kg) due to the lack of genotype variation in the group at these markers. Muscled breeds include the Boston Terrier (BOST), French Bulldog (FBUL), Miniature Bull Terrier (MBLT), Staffordshire Bull Terrier (STAF), Chinese Shar-pei (SHAR), Bulldog (BULD), Chow-Chow (CHOW), American Staffordshire Terrier (AMST), Boxer (BOX), Beauceron (BEAU), Bullmastiff (BULM), Bernese Mountain Dog (BMD), Rottweiler (ROTT), Leonberger (LEON), Tibetan Mastiff (TIBM), Neapolitan Mastiff (NEAM), Newfoundland (NEWF), Dogue de Bordeaux DDBX), English Mastiff (MAST) and Saint Bernard (STBD).</p

Observed genotypes for the ten most strongly associated variants identified in large dogs using WGS data.

<p>The three first columns correspond to the dog, breed, sex and standard breed weight (SBW). The next 10 columns correspond to the 10 most strongly associated variants at locus 1, identified from WGS data. The first part of the table corresponds to large dogs (SBW >41 kg). Homozygous and hemizygous genotypes for the “large allele” are colored in red, homozygous/hemizygous genotypes for the “small/medium” allele are colored in blue and heterozygous genotypes are colored in yellow. The second part of the table shows the distribution of the “large allele” in the 140 dogs with a SBW ≤41 kg. Values correspond to the percentage of this control population showing each genotype by variant. The last row shows the respective p-value estimated (Wald test) for each variant.</p

Best SNP markers associated with SBW above 41 kg in dogs.

<p>Best SNP markers associated with SBW above 41 kg in dogs.</p

Zebrafish cranioskeletal development requires Bmp3 function.

<p>(A–H) Wholemount RNA <i>in situ</i> hybridization of <i>bmp3</i> expression at 48 hpf (A,B), 72 hpf (C), and 96 hpf (D) stages. Anterior to the left. (A) Dorsal view, (B–D) lateral view. Pharyngeal arches indicated by brackets, pectoral fins by red arrowheads. Wholemounts (E,H,K) and alcian blue cartilage stains (F,G,I,J,L,M) of 96 hpf embryos from uninjected (E–G) and morpholino-injected embryos (h–j, mild phenotype, n = 72/177; k–m, severe phenotype, n = 83/177). Phenotypic severity is distinguished by tail curling (compare insets). Loss of jaw structures (black arrows) and frontal bossing (white arrowheads) is apparent in both classes of morphants. Cartilage is severely dysmorphic, hypoplastic, or absent following Bmp3 knockdown. Abbreviations correspond to ceratobranchial (cb), ceratohyal (ch), eythmoid plate (ep), hyosymplectic (hs), Meckel's (m), palatoquadrate (pq), and trabeculae (tr) cartilages.</p

Quantitative and qualitative assessments of PC1 on canine cranioskeletal shape.

<p>(A) Gray wolf (mesocephalic, ancestor to dogs) (B) Afghan hound (dolichocephalic), (C) Leonberger (mesocephalic), (D) Pug (brachycephalic). (E) Boxplots of PC1 (corresponding breed names are listed in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002849#pgen.1002849.s008" target="_blank">Table S2</a>). (F) Surface scans of a gray wolf skull illustrate morphological changes associated with PC1. Columns (left to right) are dorsal, lateral, and rostral views. Top row: a gray wolf skull morphed by positive PC1. Middle row: a gray wolf skull (no morphing). Bottom row: a gray wolf skull morphed by negative PC1. Pseudocoloring of the gray wolf skull indicates rostrum (ros) and neurocranium (nc). Line indicates width of the zygomatic arches (za).</p