Enhancing Cattle Health: The Transformative Role of Genomic Tools in Infectious Disease Management

Infectious diseases impose a substantial economic burden on the global cattle industry, necessitating effective countermeasures beyond traditional approaches such as vaccines and antibiotics. This review explores the revolutionary impact of next-generation sequencing (NGS) in cattle health, highlighting its applications in disease profiling, host-pathogen interactions, treatment development, breeding programs, and the challenges it presents.

Introduction:

Infectious diseases significantly affect the cattle industry’s economic productivity, leading to increased treatment costs, reduced performance, and higher mortality rates. Bovine respiratory disease (BRD) exemplifies this impact, causing a staggering $3 billion annual economic loss in the U.S. Despite the financial burden and reliance on traditional interventions like vaccines and antibiotics, there is a growing concern about rising resistance. Next-generation sequencing (NGS) emerges as a transformative tool, offering opportunities to address these challenges and revolutionize disease management in the cattle sector.

Overview of Genomic Tools:

NGS revolutionizes cattle industry research by rapidly accumulating extensive genomic, transcriptomic, and epigenetic data. This comprehensive approach aids in unraveling the complex interactions within the host, microbiome, virome, and pathogens. The resulting data contribute to disease understanding, classification, and the development of advanced diagnostic and management strategies. NGS enables precise pathogen identification, facilitating tailored treatment regimens and enhancing disease tracking and eradication efforts. The technology also plays a crucial role in host-pathogen interaction studies, paving the way for diagnostic biomarkers, genomic alterations, and breeding programs for robust animals.

Pathogen Identification and Disease Profiling:

NGS proves to be a powerful tool for precise pathogen identification and understanding disease etiology. The technology aids in disease diagnosis by unraveling the genetic makeup and expression of pathogens, as demonstrated in the identification of a rare mastitis-causing microorganism in a Polish Holstein–Friesian herd. In complex diseases like BRD, where multiple pathogens complicate diagnosis, NGS reveals intricate interactions, emphasizing the need for precise pathogen identification. Geographical comparisons using NGS highlight regional differences in disease distribution, guiding tailored treatment regimens. Moreover, the technology facilitates disease tracking and eradication, exemplified by the success of the BVDV-eradication campaign in Norway.

Host-Pathogen Interaction and Microbiome Influence:

NGS facilitates in-depth exploration of the intricate interplay between pathogens and hosts, extending to host microbiome and virome influences on disease. Genome expression analysis provides insights into infectious disease management, uncovering host and pathogen gene functions and paving the way for biomarker development. Comparative analysis of infected bovine macrophages reveals unique immune responses, shedding light on pathogen-specific molecular interactions. NGS’s utility is exemplified in diagnosing novel diseases through whole blood RNA-Seq. Additionally, NGS provides a platform for exploring miRNA expression profiles as biomarkers and investigating the impact of pathogens on the host microbiome and virome.

Treatment Development:

Accumulated knowledge of disease etiology is crucial for developing effective prophylactic and symptomatic treatments in cattle. NGS plays a pivotal role in identifying immunogenic characteristics through reverse genetic manipulation of pathogen genomes, informing the development of more efficacious vaccines. Genetic engineering based on genomic insights leads to innovative therapies, exemplified by live virus BRSV and BHV-1 vaccines. Understanding microbial genetics supports antibiotic development, curbing unnecessary use and addressing resistance. NGS identifies resistance genes, guides antibiotic choices, and contributes to breeding for robust animals. For gastrointestinal nematodes, sequencing informs tailored treatments and uncovers potential drug targets.

Breeding Programs:

Genomic information aims to enhance breeding for robust animals, especially in the dairy sector, where genomic testing accelerates genetic progress. Genomic breeding demonstrates rapid gains in lifetime profitability and identifies genes associated with disease resistance. Whole-genome sequencing reveals signatures of selection related to pathogen resistance, facilitating the selection of animals with enhanced immunity. The polygenic nature of resistance is highlighted in studies on tuberculosis, Bovine Respiratory Disease, and mastitis. Genomic advancements support the breeding of robust animals with improved disease resistance.

Epigenetic Non-Mendelian Inheritance:

Epigenetic regulation, particularly imprinting, gains attention in cattle research. Sequencing epigenetic information in bull semen may offer clues for optimal breeding programs. Studies associate imprinted genes like NESP55 and RASGRF1 with somatic cell count in cattle. Cattle populations exhibit SNP variability linked to epigenetic genes, suggesting a potential area for livestock breeding research. Understanding how environmental factors influence phenotypic traits through epigenetics can improve animal management, offering insights for predicting future health-related phenotypes.

Challenges:

The challenges of NGS in livestock breeding involve data complexity and utility costs. Genomic studies and technological advancements are addressing these challenges, reflected in decreasing sequencing costs and emerging bioinformatics tools. Accurately predicted breeding values depend on reference population size and measured phenotype accuracy. Balancing economic traits without compromising critical ones is crucial. To improve disease resistance, comprehensive recording of health traits, combining data from various sources, is essential. Whole-genome sequencing enhances prediction accuracy but faces challenges in studying epigenetic and structural variations.

Conclusion:

NGS offers profound insights into the genetic basis of complex phenotypes in infectious diseases, revolutionizing disease profiling, treatment development, and breeding programs. Applications include diagnostic pathogen profiling, biomarker development, and novel treatments based on genomic insights. The integration of sequencing tools into multidisciplinary studies holds the potential to alleviate the economic burden of disease diagnosis and treatment in the cattle industry, benefiting animal health and producers. The transformative impact of NGS underscores its importance in advancing cattle research and improving overall herd well-being.