Use of LDLA for refining the confidence interval of a QTL influencing milk protein on OAR 3

Studying a commercial population of Spanish Churra sheep, we had previously identified a highly significant quantitative trait locus (QTL) for milk protein percentage (PP) on sheep chromosome 3 (OAR3). The initial confidence interval estimated for this QTL spanned 40 cM of the chromosome length. With the aim of replicating and refining this QTL, we genotyped 14 new half-sib families of Spanish Churra sheep including 1,661 ewes for 21 microsatellite markers mapping to OAR3. The new linkage analysis (LA) performed identified the presence of a highly significant QTL for PP near marker KD103 (Pc < 0.001; Pexp < 0.001) that explained 2.74% of the phenotypic variance of the trait. Two segregating families for the target QTL were identified in this new population. To enhance the resolution of the QTL mapping we performed a combined linkage disequilibrium and linkage analysis (LDLA) which narrowed the confidence interval (CI) to a 13 cM-long region (133 to 148.5 Mbp of OAR3 according to the Ovine Genome Assembly v. 2.0). Some of the positional candidate genes identified in this region were HDAC7, VDR, ENDOU, IGFBP6, AQP5, ARF3, LALBA and IRAK4. Among these genes, LALBA (alpha-lactalbumin), which encodes a major whey protein found in milk that participates in lactose synthesis, appears as a strong functional candidate for the QTL studied. These results confirm the segregation of the previously identified OAR3 QTL that influences PP in Spanish Churra sheep and define the new genomic interval and candidate genes that deserve further research efforts.