Mutations and sequence variants in GDF9, BMP15, and BMPR1B genes in Maremmana cattle breed with single and twin births

Abstract

The families of TGF-β (transforming growth factor-β) proteins are the most important growth factors in the ovary, and three related oocyte-derived members, namely GDF9 (growth differentiation factor 9), BMP15 (bone morphogenetic protein 15), and BMPR1B (bone morphogenetic protein receptor 1B), have been shown to be essential for follicular growth and ovulation. Although the essential role of these genes in determining litter size in sheep and mouse and in controlling folliculogenesis in human has been demonstrated, there is limited information on their action in other species, especially in bovine. Bovine is a monotocous specie, as humans, with one or sometimes two newborns per birth. The twinning is a complex trait determined by both genetic and environmental factors. This study aimed at investigating the nucleotide sequences of different fragments of GDF9, BMP15, and BMPR1B genes in Maremmana cows reared in Castelporziano Presidential Estate (Rome). In this herd, in the period between 1996 and 2008, a twinning rate of 12 % (on average) was observed. We identified nine single-nucleotide polymorphisms (SNPs), five in the coding region, and four in the noncoding region: Two polymorphisms caused non-synonymous mutations, g.6045 G>A (V202I) in the BMP15 gene, and g.231 T>C (L66S) in GDF9 gene. The mutation L66S was found only in cows with double birth. In the literature, there are different evidences that mutations in proregion of GDF9 protein could affect its correct function. A relationship between mutations in this region of protein and granulosa cells proliferation and oocyte development was hypothesized.