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Background  We previously localized a quantitative trait locus (QTL) on bovine chromosome 6 affecting milk production traits to a 1.5-Mb region between  BMS483  and  MNB-209  via genome scanning followed by fine mapping.    Results  Totally 15 genes were mapped within such linkage region through bioinformatic analysis of the cattle-human comparative map and bovine genome assembly. Of them, the UDP-glucose dehydrogenase ( UGDH ) was suggested as a potential positional candidate gene for milk production traits based on its corresponding physiological and biochemical functions and genetic effects. By sequencing all the coding exons and the untranslated regions in  UGDH  with pooled DNA of 8 sires represented the separated families detected in our previous studies, a total of ten SNPs were identified and genotyped in 1417 Holstein cows of 8 separation families. Individual SNP-based association analysis revealed 4 significant associations of SNP Ex1-1, SNP Int3-1, SNP Int5-1, and SNP Ex12-3 with milk yield (P < 0.05), and 2 significant associations of SNP Ex1-1 and SNP Ex12-3 with protein yield (P < 0.05). Furthermore, our haplotype-based association analyses indicated that haplotypes G-C-C, formed by SNP Ex12-2-SNP Int11-1-SNP Ex11-1, T-G, formed by SNP Int9-3-SNP Int9-2, and C-C, formed by SNP Int5-1-SNP Int3-1, are significantly associated with  protein percentage  (F=4.15; P=0.0418) and  fat percentage  (F=5.18~7.25; P=0.0072~0.0231). Finally, by using an  in vitro  expression assay, we demonstrated that the A allele of SNP Ex1-1 and T allele of SNP Ex11-1of  UGDH  significantly decreases the expression of UGDH by 68.0% at the RNA, and 50.1% at the protein level, suggesting that SNP Ex1-1 and Ex11-1 represent two functional polymorphisms affecting expression of  UGDH  and may partly contributed to the observed association of the gene with milk production traits in our samples.    Conclusions  Taken together, our findings strongly indicate that  UGDH  gene could be involved in genetic variation underlying the QTL for milk production traits.

Detection of genetic association and functional polymorphisms of UGDH affecting milk production trait in Chinese Holstein cattle