Genetic insights into bovine spastic syndrome (Crampy) in Holstein dairy cattle.

Abstract

Bovine spastic syndrome, known as Crampy, is a neuromuscular disorder in cattle. Affected cattle, 2 yr or older, suffer from involuntary muscle spasms in their hind limbs, leading to discomfort and reduced mobility. This often results in early culling from the herd, causing substantial financial loss for producers. Given the welfare implications and economic burden associated with Crampy, it is crucial to identify effective strategies to mitigate its occurrence. In this study, we assessed the feasibility of genetic selection to reduce Crampy by estimating variance components, evaluating the effect of incorporating genomic information, investigating Crampy's relationship with other economically important traits, and identifying genomic regions associated with Crampy in Canadian Holstein dairy cattle. A dataset comprising 54,826 animals, including 1,952 cases of Crampy, from 678 Canadian dairy herds, was provided by Lactanet Canada (Guelph, ON, Canada). Of these animals, 22,408 (including 408 with Crampy) were genotyped. Both threshold and linear models were used to estimate variance components, with observed scale hestimates ranging from 0.057 to 0.085. The inclusion of genomic data significantly increased the reliability of breeding values by 5% to 17%. Through a GWAS using GCTA software, a total of 41 significant SNPs were found to be significantly associated with Crampy. Functional analysis revealed 44 genes, among which we have highlighted the genes WNK2 (BTA8), DTNBP1 (BTA23), and ADK (BTA28), which have been associated with ion transport, muscle function, and neuron signaling, respectively. Enriched colocated QTL annotations linked to ketosis, muscle calcium content, and muscle zinc content were also identified, highlighting the role of metabolic processes and mineral homeostasis in muscle function. Breeding value correlations between Crampy and production, health, longevity, and type traits, and the selection indices were moderately low but favorable, indicating that current breeding strategies may indirectly select against Crampy. These findings highlight genomic selection as a viable strategy to mitigate Crampy in Canadian dairy herds, emphasizing the need for continued phenotyping for this disorder and optimization of breeding practices to improve animal welfare and sustainability.