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Data S1. Mechanism of graying, MC1R signaling, coat color and melanoma.

Data S2. Methods.

Figure S1. Testing for the effect of MC1R genotype.

Figure S2. Previously reported effect of the ASIP mutation on melanoma grade (a)1, and 2 hypotheses tested for the effect of MC1R on melanoma risk and grade in gray horses (STX17GG or STX17Gg) (b, c).

Table S1. Melanoma grading system (Rosengren et al, [5]).

Table S2. Allele coding for each genetic model was considered in regression analyses. Additive, recessive and dominant coding is relative to the derived (mutant) allele. Both dominant and recessive coding have two levels of effect: 0 or 1. Additive coding allows each additional copy of the risk allele to result in a simple additive increase in risk, with three different levels of effect: 0, 1 or 2. Genotypic coding also allows for three different levels of effect (one for each genotype), however the effect differences do not have to be additive; in this circumstance the genotype coding is categorical. For example, genotypes AA, Aa, and aa, could have effects of 0, 2 and 6 respectively, or in a scenario where heterozygotes had the highest risk effects for AA, Aa, and aa could be 0, 6 and 2 respectively. The genotypic model treats all three genotypes as independent categories, without assigning an a priori guess as to the effect (ie does not have to be additive, dominant or recessive).

Table S3. Distribution of melanoma grades in the case cohort.

Table S4. Breakdown of melanoma prevalence and mean melanoma grade by gender.

Table S5. Breakdown of melanoma prevalence and mean melanoma grade by age.

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