41 A preliminary investigation of candidate genes from a GWAS identified QTL for relative body size in the American Quarter Horse

Abstract

Artificial selection during domestication has influenced an array of morphological traits in the horse, many that are now important economic traits for the horse industry. Growth and skeletal phenotypes impact the desirability and function of horses in diverse disciplines and are often key characteristics in the development of breeds. Skeletal traits also impact functionality: benefitting horses for specialized work or predisposing them to musculoskeletal injury. To investigate variations in body size and shape, we utilized measurements taken at 2 years of age (+/− one week) from 91 American Quarter Horses bred and owned by the University of Florida. We summarized 32 body measures from each horse using a principal component analysis followed by a varimax rotation. Factor 1 summarizes 19.5% of the variation and describes overall body size, except for head measurements which are better captured in Factor 2. Factor 1 traits encompass body proportions, heavily loading on the measure's height at dock and croup. DNA was extracted from blood and hair through previously published methods and genotyped at GeneSeek Inc. (Lansing, MI) using the Affymetrix Axiom Equine HD 670k array. We recently reported results from a preliminary genome-wide association study with 311,085 high-quality SNPs (poly-high resolution, MAF >0.05)suggesting a quantitative trait locus for the Body Factor 1 trait on chromosome 6 (raw P = 1.356e-09, Bonferroni P = 4.51e-07) and defines a candidate region spanning 1.5Mb. The QTL is in a region unrelated to a previously characterized HMGA2 body height locus. The candidate region contains 5 protein-coding genes, influencing human height and skeletal traits including one associated with Noonan Syndrome- a disease impacting height and facial morphology, an interesting parallel to the phenotype observed in our population. None of the 16,860 variants found in the European Nucleotide Archive for our candidate region had a functional impacted on a protein coding region. Therefore, we sequenced 2 whole genomes from American Quarter Horses to discover variants specific to the haplotype bearing this new body size QTL. Using the 10x Chromium library prep with 150bp paired end reads on an Illumina HiSeq2500, the 2 genomes totaled 1.5 billion reads. Following alignment and variant calling using the LongRanger package (v2.2, 10x Genomics Inc.), we observed 4,703 SNPs in the candidate region. Future investigation aims to investigate additional loci relevant to body morphological variations and develop predictive phenotype models in the horse.