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Open AccessArticle

A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse

1
School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington LE12 5RD, UK
2
Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UK
*
Authors to whom correspondence should be addressed.
Genes 2019, 10(11), 880; https://doi.org/10.3390/genes10110880
Received: 30 September 2019 / Revised: 25 October 2019 / Accepted: 30 October 2019 / Published: 1 November 2019
(This article belongs to the Special Issue Equine Genetics)
Exercise-induced pulmonary haemorrhage (EIPH) occurs in horses performing high-intensity athletic activity. The application of physics principles to derive a ‘physical model’, which is coherent with existing physiology and cell biology data, shows that critical parameters for capillary rupture are cell–cell adhesion and cell stiffness (cytoskeleton organisation). Specifically, length of fracture in the capillary is a ratio between the energy involved in cell–cell adhesion and the stiffness of cells suggesting that if the adhesion diminishes and/or that the stiffness of cells increases EIPH is more likely to occur. To identify genes associated with relevant cellular or physiological phenotypes, the physical model was used in a post-genome-wide association study (GWAS) to define gene sets associated with the model parameters. The primary study was a GWAS of EIPH where the phenotype was based on weekly tracheal wash samples collected over a two-year period from 72 horses in a flat race training yard. The EIPH phenotype was determined from cytological analysis of the tracheal wash samples, by scoring for the presence of red blood cells and haemosiderophages. Genotyping was performed using the Illumina Equine SNP50 BeadChip and analysed using linear regression in PLINK. Genes within significant genome regions were selected for sets based on their GeneOntology biological process, and analysed using fastBAT. The gene set analysis showed that genes associated with cell stiffness (cytoskeleton organisation) and blood flow have the most significant impact on EIPH risk.
Keywords: exercise-induced pulmonary haemorrhage; horse; genome-wide association; capillary fracture; cell–cell adhesion; cell cytoskeleton stiffness; blood flow exercise-induced pulmonary haemorrhage; horse; genome-wide association; capillary fracture; cell–cell adhesion; cell cytoskeleton stiffness; blood flow
MDPI and ACS Style

Blott, S.; Cunningham, H.; Malkowski, L.; Brown, A.; Rauch, C. A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse. Genes 2019, 10, 880.

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