The KMT2A gene: mRNA differential expression in the ovary and a novel 13-nt nucleotide sequence variant associated with litter size in cashmere goats

A genome-wide association study had shown that lysine methyltransferase 2A (KMT2A), which encodes the histone 3 lysine 4 methyltransferase and reportedly can regulate gametogenesis, steroidogenesis, and development as well as other biological processes, is a potential candidate gene influencing litter size in the dairy goat, suggesting its key function in animal reproduction. Here, we aimed to explore the genetic effects of the KMT2A gene on litter size in females of the Chinese indigenous cashmere goat, using a large sample size (n > 1,000), based on their levels of RNA transcription and DNA variation. First, mRNA expression levels of this gene in ovarian tissues between the low-prolific group (first-born litter size = 1) and high-prolific group (first-born litter size ≥2) were significantly different, revealing the potential functioning of KMT2A in goat prolific. Moreover, a novel 13-nt nucleotide sequence variant was identified in Shaanbei white cashmere goats (n = 1,616). In accordance with the independent chi-square (χ2) analysis, the distribution of genotypes (P = 2.57 × 10–9) and allelotypes (P = 3.00 × 10–7) between the low- and high-prolific groups differed significantly, indicating the 13-nt mutation was associated with litter size. Further analysis showed that the insertion/insertion (II) genotype was significantly different with insertion/deletion (ID) (P = 1.76 × 10–9) and deletion/deletion (DD) (P = 7.00 × 10–6), with goats having the DD genotype producing an average litter size larger than the other genotypes. Taken together, these findings suggest KMT2A can serve as a candidate gene for breeding goats, which may have implications for improving the future development of the goat industry.