Mutations in the MTHFR gene and their associations with milk production traits in dairy goats

• Fourteen novel SNPs were identified in goat MTHFR gene.
• The g.1951C>T and g.4800G>A loci have significant effects on milk protein.
• The combined genotypes C25 and C27 can be used in marker-assisted selection.

It is known that 5,10-methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism by irreversibly converting 5,10-methylenetetrahydrofolate into 5-methylenetetrahydrofolate, which is the predominant circulating form of folate. Thus, folate is important for milk protein synthesis and it has been suggested that MTHFR may be a key regulator of folate metabolism during milk protein synthesis within mammary epithelial cells. In this study, Xinong Saanen (SN, N = 385) and Guanzhong dairy goats (GZ, N = 327) were used to detect single nucleotide polymorphisms (SNPs) in the coding regions within the intron–exon boundaries and the proximal flanking regions of the MTHFR gene by DNA sequencing and PCR-restriction fragment length polymorphism. Fourteen polymorphisms were detected in the MTHFR gene of both dairy goat breeds (g.699A>G, g.739C>A, g.995C>T, g.1951C>T, g.1982T>C, g.2115A>G, g.2607G>A, g.2611_2612delCA, g.4800G>A, g.12118T>C, g.12353A>G, g.14064A>G, g.14084A>G, and g.14344A>G). Single SNP-trait association analysis showed that the mutations at the g.1951C>T and g.4800G>A loci had significant effects on the milk protein contents. Thus, the combined genotypes of C25 (TTCCCCGGAA) and C27 (TTTTCCGGGG) can be used for marker-assisted selection to identify individuals with higher milk protein contents in the GZ and SN breeds, respectively. These results extend the spectrum of genetic variation in the caprine MTHFR gene, thereby contributing to goat genetic resources and breeding.