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Proc Natl Acad Sci U S A. 2005 May 10;102(19):6896-901. Epub 2005 May 2.

Fine-mapping milk production quantitative trait loci on BTA6: analysis of the bovine osteopontin gene.

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  • 1Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA. schnabelr@missouri.edu


Bovine chromosome six (BTA6) harbors up to six quantitative trait loci (QTL) influencing the milk production of dairy cattle. In stark contrast to human, there is long-range linkage disequilibrium in dairy cattle, which has previously made it difficult to identify the mutations underlying these QTL. Using 38 microsatellite markers in a pedigree of 3,147 Holstein bulls, we fine mapped regions of BTA6 that had previously been shown to harbor QTL. Next, we sequenced a 12.3-kb region harboring Osteopontin, a positional candidate for the statistically most significant of the identified QTL. Nine mutations were identified, and only genotypes for the OPN3907 indel were concordant with the QTL genotypes of eight bulls that were established by segregation analysis. Four of these mutations were genotyped, and a joint linkage/linkage disequilibrium mapping analysis was used to demonstrate the existence of only two functionally distinct clusters of haplotypes within the QTL region, which were uniquely defined by OPN3907 alleles. We estimate a probability of 0.40 that no other mutation within this region is concordant with the QTL genotypes of these eight bulls. Finally, we demonstrate that the motif harboring OPN3907, which is upstream of the promoter and within a region known to harbor tissue-specific osteopontin regulatory elements, is moderately conserved among mammals. The motif was not retrieved from database queries and may be a novel regulatory element.

[PubMed - indexed for MEDLINE]
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