Fine mapping of the FecL locus influencing prolificacy in Lacaune sheep

Abstract

In the Lacaune sheep population, two major loci influencing ovulation rate are segregating: FecX and FecL. The FecX(L) mutation is a non-conservative substitution (p.Cys53Tyr) in BMP15 that prevents the processing of the protein. Using a statistical approach, FecL has been shown to be an autosomal major gene. A full genome scan localized the FecL locus on sheep chromosome 11. Fine mapping reduced the interval containing FecL to markers BM17132 and FAM117A, corresponding to a synteny block of 1.1 megabases on human chromosome 17, which encompasses 20 genes. The expression of 16 genes from this interval was observed in tissues of the reproductive axis, but expression was not affected in homozygous FecL(L) females. In this interval, a unique haplotype was associated with the FecL(L) mutation. This particular haplotype could be predicted by the DLX3:c.*803A>G SNP in the 3' UTR sequence of the DLX3 gene. This SNP provided accurate classification of animals (99.5%) as carriers or non-carriers of the mutation and therefore maybe useful in marker assisted selection. A synergistic action of FecL(L) and FecX(L) mutations on both ovulation rate and litter size was demonstrated. Until now, all the Fec genes identified in sheep belong to the bone morphogenetic protein (BMP) system. Based on the human orthologous region, none of the 20 genes in the FecL region corresponds to known molecules in the BMP system. The identification of the FecL(L) mutation could lead to the discovery of a new pathway involved in the regulation of ovulation rate.

Using sheep lines with mutations in single genes to better understand ovarian function

“…However, BMP15 mutations have also been observed in flocks carrying other putative major genes influencing ovulation rate wherein the effect is additive rather than synergistic. This includes the animals carrying the Lacaune gene (FecL L ) and the BMP15 mutation in the Lacaune breed (FecX L ) (Drouilhet et al 2009). Investigations into the underlying physiology of ewes homozygous for the Lacaune (FecL L ) gene further highlighted the fact that different physiological mechanisms appeared to be acting to increase ovulation rate in this line of ewes (Drouilhet et al 2010).…”

Genes con efecto mayor sobre la fertilidad de ovejas. Revisión

“…However, Xu et al (9) report ewes of low fertility (LF) with BMPRIB polymorphism, which suggests that other factors can participate inhibiting the phenotypic Cuadro 2. Efecto de las variantes génicas en la tasa de ovulación (OR) en ovejas Compiled from Davis (33) , Bodin et al (37) , Notter (24) , Monteagudo et al (13) , Drouilhet et al (20) , Silva et al (11) de ovulación en ovejas incrementan con el número de copias para el gen ALK6 (7) . Las ovejas que heredan una copia del gen Booroola de sus padres producen cerca de 1.5 óvulos más, y dan un cordero extra por parto (Cuadro 2).…”

“…El locus FecL se encuentra en el cromosoma 11 ovino, entre un intervalo de 2.1 cM entre los marcadores DLX3 y BM17132 (20) , o entre los marcadores BM17132 y FAM117A…”

“…El estudio de estos genes ha dado luz al conocimiento y a la exploración de las vías biológicas implicadas en el control de la ovulación en mamíferos en general (20) .…”

“…The study of these genes sheds light on the knowledge and exploration of biological routes involved in the control of ovulation in mammals in general (20) .…”