Wade Claire M
School of Life and Environmental Sciences, University of Sydney, Sydney, New South Wales, Australia.
Anim Genet. 2025 Feb;56(1):e70000. doi: 10.1111/age.70000.
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 = 2.459 × 10) and for weight it was chr3:91706639G>A (p = 9.762 × 10). 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 = 1.65 × 10; p = 1.79 × 10). 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 = 0.01). The effects on the variants assessed are limited to small variants identified in the Dog10K resource using breed-representative sizes.
迷你牛头梗和牛头梗是同一犬种的两个变种，历史上按体型划分。我们通过对69只迷你牛头梗和33只牛头梗进行分层全基因组关联分析，确定了与变种相关的染色体区域。接下来，我们利用拥有品种代表性指标的Dog10K个体的身高（N = 1458）和体重（N = 1282），评估可能影响体型的功能变异的显著性。突出显示了在多个品种中对体型有显著影响且与Dog10K中四只牛头梗和四只迷你牛头梗中观察到的体型等位基因一致的变异。在确定的五个区域中，两个区域包含已知影响犬类体型的基因，第三个区域包含一个潜在的新的身高基因（ARFGEF3）。在LCORL附近，牛头梗中与身高关联度最高的变异是chr3:91734656A>G（p = 2.459×10），与体重关联度最高的变异是chr3:91706639G>A（p = 9.762×10）。所有牛头梗（包括迷你牛头梗）在LCORL中已知的体型变异（chr3:91872822A>del）的衍生等位基因上都是单态的。在IGF2BP2的第一个外显子中，chr34:18694869 - 71ins>del处的衍生等位基因显著降低了牛头梗以及多个品种（Dog10K品种代表性身高和体重）的身高和体重（p = 1.65×10；p = 1.79×10）。ARFGEF3 chr1:30793904G>A（XP_038382065.1 p.V243I）错义变异的衍生等位基因显著降低了品种代表性身高，但对体重没有影响（p = 0.01）。对所评估变异的影响仅限于使用品种代表性体型在Dog10K资源中鉴定出的小变异。
