Insights into the genetics of body size in the Bull Terrier

Abstract

The Bull Terrier (Miniature) and Bull Terrier are two varieties of a dog breed historically divided by size. We identify variety-associated chromosomal regions identified using stratified genome-wide association analysis of 69 Bull Terriers (Miniature) and 33 Bull Terriers. Next, we assess the significance of possible functional variants for body size using height (N = 1458) and weight (N = 1282) of Dog10K individuals with breed-representative metrics available. Variants significant for size across breeds that are consistent with size alleles observed in four Bull Terriers and four Bull Terriers (Miniature) represented in Dog10K are highlighted. From five identified regions, two include genes already known to influence canine body size and a third contains a potential new height gene (ARFGEF3). Near LCORL, the most highly associated variant for height in Bull Terriers was chr3:91734656A>G (p_{Across-breed height} = 2.459 × 10⁻⁹⁹) and for weight it was chr3:91706639G>A (p_{Across-breed weight} = 9.762 × 10⁻⁸⁵). All Bull Terriers (including Miniature) were monomorphic for the derived allele at the known size variant in LCORL (chr3:91872822A>del). In the first exon of IGF2BP2, the derived allele at chr34:18694869-71ins>del significantly reduces both height and weight in Bull Terriers and across breeds (Dog10K breed representative height and weight) (p_{Across-breed height} = 1.65 × 10⁻⁹; p_{Across-breed weight} = 1.79 × 10⁻⁸). The derived allele of the missense variant in ARFGEF3 chr1:30793904G>A, XP_038382065.1 p.V243I significantly reduces breed representative height but not weight (p_{Across-breed height} = 0.01). The effects on the variants assessed are limited to small variants identified in the Dog10K resource using breed-representative sizes.