We report putative quantitative trait loci affecting female fertility and milk production traits using the merged data from two research groups that conducted independent genome scans in Dairy Bull DNA Repository grandsire families to identify quantitative trait loci (QTL) affecting economically important traits. Six families used by both groups had been genotyped for 367 microsatellite markers covering 2713.5 cM of the cattle genome (90%), with an average spacing of 7.4 cM. Phenotypic traits included PTA for pregnancy rate and daughter deviations for milk, protein and fat yields, protein and fat percentages, somatic cell score, and productive life. Analysis of the merged dataset identified putative quantitative trait loci that were not detected in the separate studies, and the pregnancy rate PTA estimates that recently became available allowed detection of pregnancy rate QTL for the first time. Sixty-one putative significant marker effects were identified within families, and 13 were identified across families. Highly significant effects were found on chromosome 3 affecting fat percentage and protein yield, on chromosome 6 affecting protein and fat percentages, on chromosome 14 affecting fat percentage, on chromosome 18 affecting pregnancy rate, and on chromosome 20 affecting protein percentage. Within-family analysis detected putative QTL associated with pregnancy rate on six chromosomes, with the effect on chromosome 18 being the most significant statistically. These findings may help identify the most useful markers available for QTL detection and, eventually, for marker-assisted selection for improvement of these economically important traits.

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 linkage͞linkage 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.linkage disequilibrium S ince the first genome scan to detect quantitative trait loci (QTL) in dairy cattle (1), QTL affecting milk production traits have been identified on almost every bovine autosome (2). A QTL proximal to the centromere of BTA14 that affects milk fat percent (FP) has consistently been identified. The causal mutation underlying this QTL has independently been identified by two groups (3, 4) as a K232A substitution in exon VIII of DGAT1 (acylCoA͞diacylglycerol acyltransferase 1). Most studies have also identified QTL on BTA6, consistently identifying a QTL affecting milk protein percent (PP) near BM143 (5). The genes and causal mutations underlying the BTA6 milk QTL have yet to be identified. However, several recent reports have focused upon the PP QTL near BM143. This QTL was localized to a 4-cM region around BM143 (55.4 cM) in an Israeli Holstein population where two additional QTL near BM415 (80.5 cM) and the centromere were also identified (6). Freyer et al. (7) reported two QTL for milk yield (MY) at 41 and 91 cM and two QTL for PP at 44 and 67 cM, as well as a QTL affecting both fat yield (FY) and protein yield (PY) at 70 cM. Olsen et al. (8) localized the FP and PP QTL near BM143 to a 7.5-cM interval bounded by BMS2508 and FBN12. Cohen et al. (9) were the first to begin sequencing candidate genes in this region and, whereas FAM13A1 appeared to be a likely functional candidate, it was excluded as underlying the QTL, which was placed centromeric of FAM13A1. This QTL has now been fine mapped to a 420-kb interval between genes ABCG2 and LAP3 (1...

Thirty weanling, crossbred barrows (SUS SCROFA) were used to determine the effects of amount and source of dietary Cu on small intestinal morphology and lipid peroxidation, Cu metabolism, and mRNA expression of proteins involved in hepatic Cu homeostasis. At 21 d of age, pigs were stratified by BW (6.33 ± 0.23 kg) and allocated to 1 of the following dietary treatments: i) control (no supplemental Cu; 6.7 mg Cu/kg), ii) 225 mg supplemental Cu/kg diet from Cu sulfate (CuSO(4)), or iii) 225 mg supplemental Cu/kg diet from tribasic Cu chloride (TBCC). Pigs were housed 2 pigs per pen and were fed a 3-phase diet regimen until d 35 or 36 of the study. During harvest, bile and liver were obtained for mineral analysis, and liver samples were also obtained for analysis of liver glutathione (GSH) and mRNA expression of Cu regulatory proteins. Segments of duodenum, proximal jejunum, and ileum were obtained for mucosal morphology, and duodenal mucosal scrapings were collected from all pigs for analysis of malondialdehyde (MDA). Duodenal villus height was reduced in CuSO(4) pigs compared with control (P = 0.001) and TBCC (P = 0.03) pigs. Villus height in the proximal jejunum of CuSO(4) pigs was reduced (P = 0.03) compared with control pigs, but ileal villus height was not affected (P = 0.82) by treatment. Duodenal MDA concentrations were greater (P = 0.03) in CuSO(4) pigs and tended to be greater (P = 0.10) in pigs supplemented with TBCC compared with control pigs. Liver Cu was greater (P = 0.01) in CuSO(4) vs. control pigs, and tended (P = 0.07) to be greater in TBCC pigs than control pigs. Bile Cu concentrations were greater (P < 0.001) in CuSO(4) and TBCC pigs vs. controls and were also greater (P = 0.04) in TBCC vs. CuSO(4) pigs. Total liver GSH concentrations were less (P = 0.02) in pigs fed diets supplemented with CuSO(4) vs. pigs fed control diets but total liver GSH did not differ (P = 0.11) between control and TBCC pigs. Hepatic mRNA of cytochrome c oxidase assembly protein 17 was less (P = 0.01) in CuSO(4) and tended to be less (P = 0.08) in TBCC pigs vs. control pigs. Expression of antioxidant 1 mRNA was greater (P = 0.04) in TBCC pigs and tended to be greater (P = 0.06) in CuSO(4) pigs compared with control pigs. Results of this study indicated that, when fed at 225 mg Cu/kg diet, TBCC may cause less oxidative stress in the duodenum than CuSO(4). Feeding weanling pigs increased Cu resulted in modulation of certain Cu transporters and chaperones at the transcription level.