Genetic estimates and genome-wide association studies of antibody response in Tanzanian dairy cattle

Luis Enrique Hernandez Castro ^1,2* Elizabeth Anne Jessie Cook ^3,4 Oswald Matika ^1,2 Isaac Joseph Mengele ^5,6 Shabani Kiyabo Motto ^5,6 Shedrack Festo Bwatota ⁵ Bibiana Zirra-Shallangwa ^1,7 Ricardo Pong-Wong ¹ James Prendergast ^1,2 Raphael Mrode ^2,8 Philip G. Toye ^3,4 Daniel Mushumbusi Komwihangilo ⁹ Eliamoni Lyatuu ¹⁰ Benedict E. Karani ^3,4 Getrude Nangekhe ^3,4 Okeyo Ally Mwai ³ Gabriel Shirima ⁵ Barend Mark Bronsvoort ^1,2*

• ¹ Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom
• ² Centre for Tropical Livestock Genetics and Health, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, United Kingdom
• ³ International Livestock Research Institute (ILRI), Nairobi, Kenya
• ⁴ Centre for Tropical Livestock Genetics and Health, Nairobi, Kenya
• ⁵ Nelson Mandela African Institution of Science and Technology, Arusha, Arusha, Tanzania
• ⁶ Tanzania Veterinary Laboratory Agency, Dar es Salaam, Dar es Salaam, Tanzania
• ⁷ Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, Scotland, United Kingdom
• ⁸ Scotland's Rural College, Edinburgh, Scotland, United Kingdom
• ⁹ Tanzania Livestock Research Institute, Dodoma, Tanzania
• ¹⁰ International Livestock Research Institute (ILRI), Dar es Salaam, Tanzania

Identifying the genetic determinants of host defence against infectious pathogens is central to enhancing disease resilience and therapeutic efficacy in livestock. Here, we investigated immune response heritability to important infectious diseases affecting dairy smallholder cattle using variance component analysis. We also conducted genome-wide association studies (GWAS) to identify genetic variants that may help understand the underlying biology of these health traits. Assessing 668,911 single-nucleotide polymorphisms (SNP) genotyped in 2045 crossbreed cattle sampled from six regions of Tanzania, we identified high levels of interregional admixture and European introgression, which may increase infectious disease susceptibility relative to indigenous breeds. Heritability estimates were low to moderate, ranging from 0.03 (SE ± 0.06) to 0.44 (SE ± 0.07), depending on the health trait. GWAS results revealed several loci associated with seropositivity to the viral diseases Rift Valley fever and bovine viral diarrhoea, the protozoan parasites Neospora caninum and Toxoplasma gondii, and the bacterial pathogens Brucella sp, Leptospira hardjo and Coxiella burnetti. The identified quantitative trait loci mapped to genes involved in immune defence, tumour suppression, neurological processes, and cell exocytosis. We propose that our results form a baseline in the future understanding of the cellular pathways contributing to general and taxon-specific infection responses, and to advance selective breeding and therapeutic target designs.