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

Blott, Sarah; Cunningham, Hannah; Malkowski, Laurene; Brown, Alexandra; Rauch, Cyril


Hannah Cunningham

Laurene Malkowski

Alexandra Brown


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.


Blott, S., Cunningham, H., Malkowski, L., Brown, A., & Rauch, C. (2019). A Mechanogenetic Model of Exercise-Induced Pulmonary Haemorrhage in the Thoroughbred Horse. Genes, 10(11),

Journal Article Type Article
Acceptance Date Oct 30, 2019
Online Publication Date Nov 1, 2019
Publication Date Nov 1, 2019
Deposit Date Nov 5, 2019
Publicly Available Date Nov 6, 2019
Journal Genes
Print ISSN 2073-4425
Electronic ISSN 2073-4425
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 10
Issue 11
Article Number 880
Keywords Genetics(clinical); Genetics
Public URL
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