Phylogenetic relationship between haplotypes at <i>MITF</i> and <i>KIT</i>.

<p>Phylogenetic relationships between haplotypes at <i>MITF</i> (M1–M6) and <i>KIT</i> (K1–K7). Haplotype combinations (hap1 = haplotype 1, hap2 = haplotype 2) and individuals average total white markings score (aTSC = average Total Score) are shown on the right.</p

Genetic variance (%) explained by the three major candidate loci.

<p>The contributions of <i>MC1R</i>, <i>KIT</i> and <i>MITF</i> were calculated separately for each locus across a 2 Mb interval.</p

Results of the logistic regression model analysis.

<p>Results of the logistic regression model analysis for the relationship between <i>MITF</i> haplotypes, SNPs across the 2 Mb <i>KIT</i> region <i>and KIT</i> haplotypes.</p

Phenotypic variation in the expression of white markings.

<p>Example of phenotypes. Horse (A) has a total score of white markings of 1 (head = 0; foreleg = 0; hind leg = 1); horse (B) has a total score of white markings of 19 (head = 9; foreleg = 2; hind leg = 8).</p

GWAS identifies two major loci associated with total white marking scores.

<p>A Manhattan plot showing the negative log of the probability of association (p-value) between individual marker and total white marking score. (A) Analysis included horses of all colors, (B) bay horses only, (C) chestnut horses only. Markers are represented in different colors according to their chromosome. Significance level of p≤1×10⁻⁸ is indicated with a dashed red line; a dashed black line represents association with p≤10⁻⁴.</p

Average total white markings score for <i>MITF-KIT</i> haplotype combinations.

<p>Average total white markings score and standard deviation for <i>MITF-KIT</i> haplotype combinations. Adjacent squares represent haplotypes (red = <i>MITF</i>; blue = <i>KIT</i>); color shades represent haplotypes of the phylogenetic relationship trees (<i>MITF</i>: M1–M6; <i>KIT</i>: K1–K7).</p

Fine-scale quantitative association mapping and linkage disequilibrium across <i>MITF</i> and <i>KIT</i>.

<p>Fine–scale quantitative association between total white markings score and linkage disequilibrium (LD) in r² between SNPs across 2 Mb regions in (A) the <i>KIT</i> and (B) the <i>MITF</i> region including all horses. The darker shading represents higher LD, black diamond’s represents an r² of 1.</p

Results of the quantitative association analysis within the major haplotype block.

<p>Results of the haplotype-based quantitative association analysis within the major haplotype block of <i>MITF</i> (M1–M6) and <i>KIT</i> (K1–K7). The analysis includes all horses used for fine mapping. Haplotype frequency, beta coefficient, p-value and empirical p-value are indicated for every investigated haplotype.</p

Variants detected by whole genome re-sequencing of an affected Labrador Retriever.

a<p>The sequences were compared to the reference genome (CanFam 3.1) from a Boxer. Only variants that were homozygous in the affected Labrador Retriever are reported.</p

Proximal melanocyte-specific promoter of the <i>MITF</i> gene.

<p>The depicted region corresponds to positions −89 to +1 with respect to the transcription start site and is in reverse complementary orientation to the genomic reference sequence (ECA16:20,117,350–20,117,261; EquCab2.0). The three vertical red lines in the dog and mouse sequences represent small insertions. In some splashed white horses, an 11 bp motif shown in red replaces an adenine, which is part of a highly conserved PAX3 transcription factor binding site in the wild-type sequence. The inserted 11 bp sequence may have arisen by duplication from an identical sequence motif a few nucleotides further downstream (underlined).</p