Identifying Candidate Genes for Mastitis Resistance Using Ovine Transcriptome

Mastitis is the most prevalent disease in dairy sheep with major economic and welfare implications. Mastitis resistance in cattle and dairy sheep is known to be heritable, and selective breeding offers one route of control. A mastitis-specific DNA array was available based on previous discovery of common Quantitative Trait Loci (QTLs) in distinct dairy sheep populations. Using this array, we performed Genome-Wide Association Studies of four mastitis traits in 609 Greek Chios dairy ewes. Five QTLs were detected. To identify possible protein-coding genes associated with the detected QTLs, we used two sources of transcriptomic data; an expression atlas derived from cross-bred meat sheep (Scottish Blackface x Texel) based upon the large-scale mRNA sequencing of multiple tissues and cell lines, and a comparative study of transcription in the milk somatic cells of two Spanish dairy breeds (Churra and Assaf). The sheep atlas dataset contains expression profiles from sheep bone marrow derived macrophages (BMDMs) grown in macrophage colony-stimulating factor (CSF1; which is highly-expressed in lactating mammary gland) and stimulated with bacterial lipopolysaccharide (LPS, a model for response to gram-negative pathogens. Within the QTL regions, 14 genes were inducible by LPS, highly expressed in milk somatic cells and had expression levels associated with somatic cell count. Half of these genes were also previously associated with mastitis resistance in dairy cattle. The results suggest that variation in macrophage response to pathogen-associated molecules underlies susceptibility to mastitis in dairy animals.