Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of order SB 202190 ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region get ONO-4059 containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.Th26 and skeletal development27, respectively. Selective sweep on Oar6 . The Oar6 selective sweep contains several genes that may have been affected by selection i.e. the non-SMC condensin I complex, subunit G (NCAPG, 37.2 Mb), the ligand dependent nuclear receptor corepressor-like (LCORL, 37.3 Mb), the leucine aminopeptidase 3 (LAP3, 37.1 Mb) and the ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2, 36.5 Mb) loci. Indeed, the NCAPG/LCORL gene pair has been reported as a selection target in many genome scans. LCORL is a co-repressor of ligand-regulatable transcriptional factors, such as the estrogen and thyroid hormone receptors, and plays a fundamental role in hepatic lipogenesis28. More importantly, variation at LCORL has been associated with height in humans29 and horses30, and with vertebrae number in pigs31. Similarly, NCAPG plays a key role in mitotic cell division and affects post-natal growth32. Other genes of interest are ABCG2, a molecule transporter that has been associated with milk yield and composition33, and LAP3. This latter gene displays a selection signature in Holstein cattle and its variability is associated with diverse milk traits24. Interestingly, the bovine chromosome 6 region containing LCORL, NCAPG, LAP3 and ABCG2 overlaps with several quantitative trait loci for growth, carcass quality, feed efficiency, reproduction and milk traits34?7.Scientific RepoRts | 6:27296 | DOI: 10.1038/srepwww.nature.com/scientificreports/At this point, is difficult to know if selection on Oar6 is targeting one or several loci. In principle, we would favour this second scenario because data generated by us and others evidence that the size of the Oar6 region under selection is considerably large suggesting that it may have been produced by the superposition of several overlapping peaks (Fig. 4). The multiple associations with production traits observed in cattle would also favour this hypothesis, although we cannot rule out the possibility of selection acting on a single gene with pleiotropic effects. Selective sweep on Oar13. Within the Oar13 selective sweep (68?4 Mb), there are two genes related with lipid metabolism i.e. the fat storage-inducing transmembrane protein 2 (FITM2, 72.3 Mb) and the acyl-CoA thioesterase 8 (ACOT8, 74.1 Mb) loci. The FITM2 protein is located in the endoplasmic reticulum and induces the packaging of triglycerides as lipid droplets38. This mechanism could be of importance in the mammary gland, since lipids are secreted as droplets that bud from the epithelial cells. The ACOT8 molecule hydrolyzes medium- to long-chain acyl-CoAs and its overexpression has been shown to abolish peroxisomal fatty acid -oxidation and enhance lipid accumulation in droplets39. Thus, these two loci may have effects on milk lipid content. Though Spanish sheep have not been specifically selected for milk fat content, the negative and moderate correlation of this trait with milk yield offers a possible explanation for our findings.improvement of Spanish sheep for milk traits. Latxa and Churra sheep produce around 180 kg (in 140 days) and 117 kg (in 120 days) of milk (Spanish Ministry of Agriculture, Food and Environment web, http://www.magrama. gob.es), respectively. Certainly, these numbers are significantly lower than milk yield registers of cosmopolitan highly specialized breeds (e.g. Lacaune sheep produce 350 kg milk in 150 days). However, in the last two decades the milk production of Spanish dairy sheep breeds has b.
