Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 23, 2005
Publication Date: May 10, 2005
Citation: Schnabel, R.D., Jong-Joo, K., Ashwell, M.S., Sonstegard, T.S., Van Tassell, C.P., Connor, E.E., Taylor, J.F. 2005. Fine-mapping milk production quantitative trait loci on bta6: analysis of the bovine osteopontin gene. Proceedings of the National Academy of Sciences. 102:6896-6901.
Interpretive Summary: Quantitative Triat Loci (QTL) affecting milk production traits have been identified on almost every bovine chromosome (Chr). Most studies identified QTL on Chr 6 affecting milk protein percent (PP) near the middle of the chromosome. The genes and causal mutations underlying this QTL were not yet identified. Our research along with that from groups in Norway and Isreal had narrowed down the region of Chr 6 containing this QTL for percent protein to a 420 kb interval between genes ABCG2 and LAP3. Only four human genes were know to reside in this region: IBSP, MEPE, OPN and PKD2. In this study, we investigate Osteopontin (OPN) as a functional candidate for this QTL, because expression in murine mammary gland is dependent on stage of postnatal development suggesting a role for OPN in mammary involution. Here we present evidence based on genetic analysis and sequencing of OPN that a putative quantitative trait nucleotide (QTN) in the upstream regulatory region of bovine OPN was identified with significant effects on milk yield, fat and protein percentage. This QTN could be used to develop marker-assisted selection programs to develop animals with either higher milk yield or greater component percentages per volume of milk.
BTA6 harbors several QTL responsible for variation in milk production traits in dairy cattle. To fine-map these QTL we genotyped 3,147 bulls from 45 half-sib families for 38 markers. Across-family LK and LD analyses indicated the presence of from 3 to 5 QTL on BTA6 influencing milk production traits. Half-sib family analyses identified 26 sires segregating for at least one QTL at chromosome-wide P<0.05. Osteopontin was identified as a positional candidate for the most significant of the identified QTL. The entire OPN gene and 5 kb upstream was sequenced from four segregating and four non-segregating sires. Nine SNPs were identified, however, only OPN3907 was concordant with the segregation status of all eight sires. The OPN3907 T9 allele significantly increases MY but marginally decreases FY and PY resulting in a significant reduction in FP and PP. LD analyses suggest the presence of two QTL and revealed strong LD in the 6 cM interval harboring OPN.