Genetic Mapping of Novel Loci Affecting Canine Blood Phenotypes.

Michelle E White,Tracy Stokol,Jessica J Hayward,Adam R Boyko,William J Murphy

doi:10.1371/journal.pone.0145199

Michelle E White, Tracy Stokol + Show 3 more

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https://doi.org/10.1371/journal.pone.0145199

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Abstract

Since the publication of the dog genome and the construction of high-quality genome-wide SNP arrays, thousands of dogs have been genotyped for disease studies. For many of these dogs, additional clinical phenotypes are available, such as hematological and clinical chemistry results collected during routine veterinary care. Little is known about the genetic basis of variation in blood phenotypes, but this variation may play an important role in the etiology and progression of many diseases. From a cohort of dogs that had been previously genotyped on a semi-custom Illumina CanineHD array for various genome-wide association studies (GWAS) at Cornell University Hospital for Animals, we chose 353 clinically healthy, adult dogs for our analysis of clinical pathologic test results (14 hematological tests and 25 clinical chemistry tests). After correcting for age, body weight and sex, genetic associations were identified for amylase, segmented neutrophils, urea nitrogen, glucose, and mean corpuscular hemoglobin. Additionally, a strong genetic association (P = 8.1×10−13) was evident between a region of canine chromosome 13 (CFA13) and alanine aminotransferase (ALT), explaining 23% of the variation in ALT levels. This region of CFA13 encompasses the GPT gene that encodes the transferase. Dogs homozygous for the derived allele exhibit lower ALT activity, making increased ALT activity a less useful marker of hepatic injury in these individuals. Overall, these associations provide a roadmap for identifying causal variants that could improve interpretation of clinical blood tests and understanding of genetic risk factors associated with diseases such as canine diabetes and anemia, and demonstrate the utility of holistic phenotyping of dogs genotyped for disease mapping studies.

Highlights

Numbers of genome-wide association studies (GWAS) in humans and other organisms have increased rapidly as dense single-nucleotide polymorphism (SNP) arrays have become more common and cost-effective and as improved genome annotation and statistical methods have increased the power of these studies[1]
The genotype data and ALT data come from different sets of dogs, we find a significant correlation between mean ln(ALT) by breed versus the allele frequency for the CFA13 locus (P < 0.034) with breed-average ln(ALT) decreasing with increasing frequency of the derived allele (Fig 3)
We have shown that we can detect significant genetic associations with 9 blood hematological and clinical chemistry test phenotypes using just 353 canine samples

Summary

Introduction

Numbers of genome-wide association studies (GWAS) in humans and other organisms have increased rapidly as dense single-nucleotide polymorphism (SNP) arrays have become more common and cost-effective and as improved genome annotation and statistical methods have increased the power of these studies[1]. In dogs, these studies have focused on identifying causal variants and risk factors for genetic disease as well as mutations underlying morphological traits like body size and coat color[2]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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