Exploring the genetic cause of myotonic dystrophy in horses

Abstract: Myotonic Dystrophy (MD) is an inherited neuromuscular disorder that leads to a wide range of clinical signs including stiffness, abnormal muscle relaxation, and muscle atrophy or hypertrophy. Affected muscles develop a prolonged contracture in response to percussion of the muscle and show waxing and waning complex repetitive discharges in electromyography (EMG). Two genetic mutations underlie the genetic basis for MD in humans that cause abnormal RNA processing. There are a limited number of case reports of MD in horses in the veterinary literature and its genetic cause is unknown. By analysing whole genome sequencing (WGS), RNAseq, and proteomics data from horses in our MD dataset, we aim to identify the molecular mechanisms contributing to the condition. Understanding the molecular mechanisms behind MD may lead to non-invasive diagnostic tests and potentially therapeutic strategies. MD horses and seven age, sex and breed-matched controls were low pass Whole genome sequenced to approximately 4X coverage. Fst values were calculated and 6 chromosome regions on ECA 1, 3, 6, 7, 16 and 18 appeared higher than our threshold of 0.0005% and conserved across multiple window sizes. On chromosome 3 was found a candidate gene responsible for the Facioscapulohumeral Muscular Dystrophy 1 in human. SNPs were investigated and one splice variant has been identified. Sequencing depth will be increased on the same horses to confirm the preliminary findings. The obtained results of this project may also provide insights into the related human MD disease, which affects an average of 1 out of 8000 individuals. As a complementary study within the main investigation, an allele frequency analysis was conducted on a specific variant located on ECA 3. Whole-genome sequencing data of horses were retrieved from NCBI, and alignment of the exon harbouring the variant was performed followed by genotyping of each horse. A distinction was observed between Endomorph (muscular) and Ectomorph (lean) horses, with different alleles linked to the horses' morphological characteristics. However, further analysis is warranted due to the limited dataset and time constraints involved in this study.