Exploring the genetics underpinning dynamic laryngeal collapse associated with poll flexion in Norwegian‐Swedish Coldblooded Trotter racehorses

Abstract

Summary Background Dynamic laryngeal collapse (DLC) associated with poll flexion is the most common disorder of the upper respiratory tract (URT) in the Norwegian‐Swedish Coldblooded Trotter (NSCT). The disorder, which has also been diagnosed in other breeds of trotters and gaited horses, appears to be related to anatomic phenotypes and only occurs during poll flexion when the horse is exercised ‘on the bit’. Objectives Identify genomic regions associated with DLC in the NSCT by combining a rigorous phenotyping protocol with genomic data from a high‐density equine genotyping array. Study design Prospective case/control study. Methods High‐speed treadmill endoscopy was used to phenotype horses (n = 61) for DLC, distinguishing between cases and controls. Genome‐wide association (GWA) analysis of DLC status was then performed using a principal component approach (PCA) with haplotype analyses subsequently performed for regions containing single‐nucleotide polymorphisms (SNPs) above the suggestive genome‐wide significance (GWS) threshold (P<1.0 × 10−5). Results One region containing 10 SNPs (Equus caballus chromosome [ECA] 7: 89,601,935–94,647,192) was above the suggestive GWS threshold. Two inferred haplotypes in this region demonstrated significant differences (P<0.001) between cases and controls, with the most frequent haplotype resulting in a significantly increased risk of DLC. Main limitations Small sample size as a result of stringent phenotyping protocols. Conclusions The current study highlights a candidate genomic region on ECA7 as potentially important with regard to the manifestation of DLC. Further exploration of this region and the genes included within it will bring veterinarians and researchers closer to fully understanding the biological mechanisms underlying DLC in horses.

Science‐in‐brief: Genomic and transcriptomic approaches to the investigation of equine diseases

“…A value of λ GC = 1 indicates no stratification, whereas λ GC > 1 indicates stratification 13 . In the Velie et al study, 9 λ GC = 1.13, demonstrating some degree of population stratification even within one breed. Visualisation of multidimensional scaling plots will also identify subpopulations within cases and controls (see Figure 2 9 ).…”

“…One of the most crucial components of any GWAS is stringent phenotyping of both case and control populations 8 . This focus on rigorous phenotyping was highlighted in the recent GWAS for the dynamic laryngeal collapse in Norwegian‐Swedish Coldblooded Trotter racehorses 9 . This dynamic airway obstruction cannot be observed during resting endoscopy and, with exercising endoscopy, is only observed when horses are exercised with tension on the bit and reins 10 .…”

“…This dynamic airway obstruction cannot be observed during resting endoscopy and, with exercising endoscopy, is only observed when horses are exercised with tension on the bit and reins 10 . To perform the first GWAS for this likely inherited condition, Velie et al 9 rigorously selected their study population and only genotyped horses that had undergone dynamic endoscopy with and without poll flexion. These horses were genotyped on the third‐generation 670K+ Axiom Equine Genotyping Array.…”

“…Other important considerations in GWAS are quality control of genotyping and the type of statistical analysis performed 8 . Quality control consists of excluding any SNPs or individuals that do not meet a pre‐defined quality threshold, as demonstrated in the study by Velie et al 9 For association testing, traits can be considered quantitative or binary trait (ie “cases” and “controls”). There are often other important covariates that should be included in the model when testing for an association.…”

“…There are often other important covariates that should be included in the model when testing for an association. In the study by Velie et al, 9 sex was included as a fixed effect even though there does not appear to be a sex‐related component to the phenotype 11 . Additionally, population stratification, or systematic ancestry differences between cases and controls, must be evaluated in any GWAS cohort.…”