Construction of interaction networks of candidate gene protein products associated with left displaced abomasum in Holstein cows

Left displaced abomasum (LDA) is a disease of dairy cows causes significant economic losses. Clinical signs of the disease include depressed condition of the animal, decreased appetite, productivity loss, abomasum atony and gas accumulation. Its clinical signs include depression of the animal, decreased appetite, abomasal atony, gas accumulation, and decreased productivity. The genetic and metabolic mechanisms that determine these manifestations, including population differences in occurring of the disease, remain not fully understood. The aim of the study was to conduct a comprehensive analyze of the genetic and physiological aspects of left displaced abomasum. To achieve this goal, the following tasks were implemented: population stratification analysis using by genome clustering of animals, an implementation of genome-wide association study using a regression model, and construction of protein interaction networks of candidate gene products associated with LDA. The study was conducted on Holstein cows (average milk yield of 12,274 kg in 305 days of lactation) from three farms in the Leningrad Region in 2022-2023. When analyzing the structure of the cow population using the ADMIXTURE method, we did not reveal significant differences in the representation of clusters in the genomes of animals in the experimental and control groups. The absence of genomic stratification proves that certain ancestral populations do not play a significant role in the formation of a predisposition to left displaced abomasum. With the genome-wide association study using the SAIGE method, a new polymorphism associated with LDA was discovered that was located in the intron of the FYN gene. Based on the results of functional annotation of candidate genes using the STRING database (https://string-db.org/), a network of protein interactions of their products was constructed. The resulting interaction network includes both protein clusters and individual proteins. We identified three clusters consisting of the proteins we defined and proteins supplemented by the STRING database. The first cluster is associated with liver dysfunction (proteins PRKCB, SRP72, ABCB11, SOX4), the second with calcium metabolism (protein GSG1L), and the third with inflammatory reactions (proteins IFI44 and FBXL19). The network also includes proteins that have not been characterized and that may be directly or indirectly involved in the pathogenesis of left displaced abomasum in high productive cows. In general, a large number of genes involved in vital metabolic pathways are associated with the pathology in cows. According to the scientific articles and the results of our study, such genes vary significantly in different populations of Holstein cattle. The products of these genes are universal and are involved in cellular processes associated with proliferation, differentiation, migration, intercellular signaling, apoptosis and many other cellular functions. In addition, such protein products can affect the expression of other genes and some of them play a significant role in oncogenesis under certain physiological conditions. It is possible that the diversity of the described genes is associated not only with the abomasum displacement, but also with other concomitant diseases that are often diagnosed in cows with left displaced abomasum. Thus, left displaced abomasum should probably be defined as a complex polygenic disease, and the information we obtained supplements the general database on gene variants in this pathology of highly productive dairy cows and expands our understanding of its gene architecture.