Three novel single-nucleotide polymorphisms of complement component 4 gene (C4A) in Chinese Holstein cattle and their associations with milk performance traits and CH50

Complement component 4 (C4A) is a candidate gene that reflects complement activity. The primary role of this gene in the classical and lectin-activation pathways is to provide protection against bacterial pathogens. In the current study, the bovine complement C4A gene was screened for polymorphisms, and the associations of these polymorphisms with the hemolytic activity of the classical pathway (CH50), C4 serum levels, and milk performance traits were examined. Three novel single-nucleotide polymorphisms (rs 132741478: g.2994 A>G, rs 134006517: g.3508 A>G, and rs 137485678: g.3649 G>C) were detected by DNA sequencing and PCR-RFLP in 1182 Chinese Holstein cows. The rs 132741478: g.2994 A>G mutation in exon 10 led to methionine and valine exchange at position 362, whereas rs 134006517: g.3508 A>G and rs 137485678: g.3649 G>C were synonymous substitutions. The statistical analyses revealed that cows with rs 132741478: g.2994 A>G-AG and rs 137485678: g.3649 G>C-CC have significantly lower somatic cell scores (SCS, P<0.01). Homozygote cows with GAC haplotypes have the lowest SCS, whereas AAG/AAC cows have the highest. The serum concentration of C4 by ELISA and the hemolytic and antibacterial activity of CH50 were also evaluated in the current study. The results confirmed that rs 132741478: g.2994 A>G in the coding sequence of the β-chain of the bovine C4A gene is related to mastitis resistance. This polymorphism may be very important in marker-assisted selections in dairy cattle breeding programs.