Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Jennifer Lawrence,Lucy J Davison,Yu-Mei Ruby Chang,Oliver A Garden,Balazs Szladovits

doi:10.1371/journal.pone.0081288

Abstract

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition.

Highlights

The remarkable steady-state constancy of numbers of peripheral red and white blood cells reflects a network of homeostatic mechanisms that retain the status quo in health [1,2,3]
Of 7281 normal hematological profiles identified in the study period, complete information was available for 6046 dogs, 5447 of which had platelet concentrations within the reference interval
A similar pattern of change was observed in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH)

Summary

Introduction

The remarkable steady-state constancy of numbers of peripheral red and white blood cells reflects a network of homeostatic mechanisms that retain the status quo in health [1,2,3]. Recent genome-wide association studies (GWAS) of healthy humans have shown that a number of hematological parameters are associated with key genetic loci, suggesting novel regulatory pathways and candidate causative genes in hemolymphatic diseases [6,7]. The creation of distinct breeds has introduced remarkable genetic homogeneity, providing an unparalleled opportunity to dissect the genetic basis of complex traits: studies that would require thousands of human subjects typically require fewer than 100 in the dog [12,13], which is rapidly gaining traction as a model species in a number of biomedical disciplines. Certain hematological phenotypes have been recognized in dogs for many years [14,15,16,17,18,19,20,21], but no largescale, systematic studies of the phenotypic diversity of peripheral blood in this species have been undertaken. Two complementary analytical approaches identified a number of unique hematological phenotypes in this species

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