Background: Clinical mastitis is an inflammation of the mammary gland and causes significant costs to dairy production. It is unfavourably genetically correlated to milk production, and, thus, knowledge of the mechanisms that underlie these traits would be valuable to improve both of them simultaneously through breeding. A quantitative trait locus (QTL) that affects both clinical mastitis and milk production has recently been fine-mapped to around 89 Mb on bovine chromosome 6 (BTA6), but identification of the gene that underlies this QTL was not possible due to the strong linkage disequilibrium between single nucleotide polymorphisms (SNPs) within this region. Our aim was to identify the gene and, if possible, the causal polymorphism(s) responsible for this QTL through association analysis of high-density SNPs and imputed full sequence data in combination with analyses of transcript and protein levels of the identified candidate gene.
Results: Associations between SNPs and the studied traits were strongest for SNPs that were located within and immediately upstream of the group-specific component (GC) gene. This gene encodes the vitamin D-binding protein (DBP) and has multiple roles in immune defense and milk production. A 12-kb duplication that was identified downstream of this gene covered its last exon and segregated with the QTL allele that is associated with increased mastitis susceptibility and milk production. However, analyses of GC mRNA levels on the available samples revealed no differences in expression between animals having or lacking this duplication. Moreover, we detected no differences in the concentrations of DBP and its ligand vitamin D between the animals with different GC genotypes that were available for this study.
Conclusions: Our results suggest GC as the gene that underlies the QTL for clinical mastitis and milk production. However, since only healthy animals were sampled for transcription and expression analyses, we could not draw any final conclusion on the absence of quantitative differences between animals with different genotypes. Future studies should investigate GC RNA expression and protein levels in cows with different genotypes during an infection.