ACCEPTED AUTHOR VERSION OF THE MANUSCRIPT: The association of gene polymorphisms with milk production and mastitis resistance phenotypic traits in dairy cattle

The aim of this study was to evaluate the association between gene polymorphisms (SNPs) and mastitis indicators and their relationship with milk production profitability in dairy herd.A functional analysis was also performed of five genes containing the studied SNPs and those located close by. DNA was isolated from the hair bulb of 320 dairy cows kept in three herds and SNP-microarray analysis was performed. The data on 299 cows was subjected to final statistical analysis using AI-REML method with one-trait repeatability test-day animal model and pedigree information using the DMU4 package. Five from 35 SNPs significantly associated with mastitis indicators or production traits and located within a gene or no more than 500,000 nucleotides from the gene were selected for the functional and economic analysis. A questionnaire was also developed to collect associated economic data of 219 cows from three herds, such as the value of milk production and direct costs incurred over three years; this allowed the gross margin, direct profitability index and direct costs incurred to produce one liter of milk to be determined, among others. None of the five studied SNPs were related to protein content. The rs110785912(T/A), found near CXCR4, and rs136813430(T/C), located in the TLR4 gene exon, were associated with lnSCC, while rs110455063(C/G), located near IGFI, was associated with milk yield, fat and total solid contents. rs109421300(T/C), associated with fat/protein content ratio, as well as fat and total solid content, is located in the DGAT1 gene intron. rs41587003(A/C), located in the DLG2 gene intron, was associated with lactose content. The economic analysis revealed differences between the variants of the three tested SNPs. The T/C variant of the rs136813430(T/C) SNP was characterized by the highest gross margin, the highest direct profitability index and the lowest costs incurred to produce 1 liter of milk. The T/A variant of rs110785912(T/A) was related to low lnSCC and was characterized by the highest direct profitability index. In turn, the C/C variant of the rs41587003(T/C) was related to the lowest level of lactose and the highest costs of milk production. It appears that rs136813430(T/C) may be the most promising of the tested SNPs for increasing the profitability of milk production. To our knowledge, it is the first effort to assess directly a correlation between the DNA polymorphism and economic output of a dairy enterprise.