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Rennet-induced milk coagulation is an important trait for cheese production. Recent studies have reported an alarming frequency of cows producing poorly coagulating milk unsuitable for cheese production. Several genetic factors are known to affect milk coagulation, including variation in the major milk proteins; however, recent association studies indicate genetic effects from other genomic regions as well. The aim of this study was to detect genetic variation affecting milk coagulation properties, measured as curd-firming rate (CFR) and milk pH. This was achieved by examining allele frequency differences between pooled whole-genome sequences of phenotypically extreme samples (pool-seq).. Curd-firming rate and raw milk pH were measured for 415 Danish Holstein cows, and each animal was sequenced at low coverage. Pools were created containing whole genome sequence reads from samples with "extreme" values (high or low) for both phenotypic traits. A total of 6,992,186 and 5,295,501 SNP were assessed in relation to CFR and milk pH, respectively. Allele frequency differences were calculated between pools and 32 significantly different SNP were detected, 1 for milk pH and 31 for CFR, of which 19 are located on chromosome 6. A total of 9 significant SNP, which were selected based on the possible function of proximal candidate genes, were genotyped in the entire sample set ( = 415) to test for an association. The most significant SNP was located proximal to , explaining 33% of the phenotypic variance. , coding for κ-casein, is the most studied in relation to milk coagulation due to its position on the surface of the casein micelles and the direct involvement in milk coagulation. Three additional SNP located on chromosome 6 showed significant associations explaining 7, 3.6, and 1.3% of the phenotypic variance of CFR. The significant SNP on chromosome 6 were shown to be in linkage disequilibrium with the SNP peaking proximal to ; however, after accounting for the genotype of the peak SNP within this QTL, significant effects (-value < 0.1) could still be detected for 2 of the SNP accounting for 2 and 1% of the phenotypic variance. These 2 interesting SNP were located within introns or proximal to the candidate genes-solute carrier family 4 (sodium bicarbonate cotransporter), member 4 () and LIM and calponin homology domains 1 (), respectively-making them interesting targets for further analysis.

We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Gottingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Gottingen minipigs were injected unilaterally into the SN with 6 per 2.5 microliters lentivirus capable of transducing cells and mediating expression of recombinant EGFP. The animals were euthanized after four (n=3) or twenty weeks (n=6). Fresh brain tissue from three animals was used for PCR. The remaining six brains were cryo- or paraffin-sectioned for fluorescence, Nissl-, and immunohistochemical EGFP visualization. EGFP was seen in nigral neurons, axons, glial cells, endothelial cells, and in nigral fibers targeting the striatum. PCR-based detection confirmed the presence of the transgene in SN, whereas all other examined brain areas were negative, indicating that the immunohistochemically detected EGFP in the striatum derived from transfected nigral cells. We aim to induce direct viral mediated gene transfer in the substantia nigra (SN) of the Gottingen minipig using MRI guided stereotaxic injections of lentiviral vectors encoding enhanced green fluorescent protein (EGFP). Nine female Gottingen minipigs were injected unilaterally into the SN with 6 per 2.5 microliters lentivirus capable of transducing cells and mediating expression of recombinant EGFP. The animals were euthanized after four (n=3) or twenty weeks (n=6). Fresh brain tissue from three animals was used for PCR. The remaining six brains were cryo- or paraffin-sectioned for fluorescence, Nissl-, and immunohistochemical EGFP visualization. EGFP was seen in nigral neurons, axons, glial cells, endothelial cells, and in nigral fibers targeting the striatum. PCR-based detection confirmed the presence of the transgene in SN, whereas all other examined brain areas were negative, indicating that the immunohistochemically detected EGFP in the striatum derived from transfected nigral cells.

Pleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker-assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait loci (QTL) or markers associated with the prevalence of CP should be identified. In this study, 7470 pigs from crosses between 12 Danish Duroc boars and 604 sows (Danish Landrace × Danish Large White) were evaluated for CP located on the dorso-caudal part of the lungs. Quantitative trait loci were identified within boar families using both a Binomial logistic regression method and a chi-square test of association. Significant QTL for CP were detected on Sus scrofa chromosomes (SSC) 2, 8, 12, 13, 14 and 18 using both methods. One QTL on SSC 8 was also detected across families. For the QTL identified within families, the odds-ratio of having CP was approximately twice as high for the unfavourable allele compared to the favourable one. These QTL and closely linked markers show promise for the development of gene-specific markers associated with a reduced incidence of CP located on the dorso-caudal part of the lungs. Udgivelsesdato: October 2010 Pleuropneumonia is a major problem in pig production. At the time of slaughter, chronic pleuritis (CP) developed from pleuropneumonia is a common finding, and breeding for a reduced incidence of CP using marker-assisted selection (MAS) would be advantageous. Before applying MAS, quantitative trait loci (QTL) or markers associated with the prevalence of CP should be identified. In this study, 7470 pigs from crosses between 12 Danish Duroc boars and 604 sows (Danish Landrace × Danish Large White) were evaluated for CP located on the dorso-caudal part of the lungs. Quantitative trait loci were identified within boar families using both a Binomial logistic regression method and a chi-square test of association. Significant QTL for CP were detected on Sus scrofa chromosomes (SSC) 2, 8, 12, 13, 14 and 18 using both methods. One QTL on SSC 8 was also detected across families. For the QTL identified within families, the odds-ratio of having CP was approximately twice as high for the unfavourable allele compared to the favourable one. These QTL and closely linked markers show promise for the development of gene-specific markers associated with a reduced incidence of CP located on the dorso-caudal part of the lungs.

A QTL study was performed in large half-sib families to characterize the genetic background of variation in pork quality traits as well as to examine the possibilities of including QTL in a marker-assisted selection scheme. The quality traits included ultimate pH in LM and the semimembranosus, drip loss, and the Minolta color measurements L*, a*, and b* representing meat lightness, redness, and yellowness, respectively. The families consist of 3,883 progenies of 12 Duroc boars that were evaluated to identify the QTL. The linkage map consists of 462 SNP markers on 18 porcine autosomes. Quantitative trait loci were mapped using a linear mixed model with fixed factors (sire, sex, herd, month, sow age) and random factors (polygenic effect, QTL effects, and litter). Chromosome-wide and genome-wide significance thresholds were determined by Peipho's approach, and 95% Bayes credibility intervals were estimated from a posterior distribution of the QTL position. In total, 31 QTL for the 6 meat quality traits were found to be significant at the 5% chromosome-wide level, among which 11 QTL were significant at the 5% genome-wide level and 5 of these were significant at the 0.1% genome-wide level. Segregation of the identified QTL in different families was also investigated. Most of the identified QTL segregated in 1 or 2 families. For the QTL affecting ultimate pH in LM and semimembranosus and L* and b* value on SSC6, the positions of the QTL and the shapes of the likelihood curves were almost the same. In addition, a strong correlation of the estimated effects of these QTL was found between the 4 traits, indicating that the same genes control these traits. A similar pattern was seen on SSC15 for the QTL affecting ultimate pH in the 2 muscles and drip loss. The results from this study will be helpful for fine mapping and identifying genes affecting meat quality traits, and tightly linked markers may be incorporated into marker-assisted selection programs A QTL study was performed in large half-sib families to characterize the genetic background of variation in pork quality traits as well as to examine the possibilities of including QTL in a marker-assisted selection scheme. The quality traits included ultimate pH in LM and the semimembranosus, drip loss, and the Minolta color measurements L*, a*, and b* representing meat lightness, redness, and yellowness, respectively. The families consist of 3,883 progenies of 12 Duroc boars that were evaluated to identify the QTL. The linkage map consists of 462 SNP markers on 18 porcine autosomes. Quantitative trait loci were mapped using a linear mixed model with fixed factors (sire, sex, herd, month, sow age) and random factors (polygenic effect, QTL effects, and litter). Chromosome-wide and genome-wide significance thresholds were determined by Peipho's approach, and 95% Bayes credibility intervals were estimated from a posterior distribution of the QTL position. In total, 31 QTL for the 6 meat quality traits were found to be significant at the 5% chromosome-wide level, among which 11 QTL were significant at the 5% genome-wide level and 5 of these were significant at the 0.1% genome-wide level. Segregation of the identified QTL in different families was also investigated. Most of the identified QTL segregated in 1 or 2 families. For the QTL affecting ultimate pH in LM and semimembranosus and L* and b* value on SSC6, the positions of the QTL and the shapes of the likelihood curves were almost the same. In addition, a strong correlation of the estimated effects of these QTL was found between the 4 traits, indicating that the same genes control these traits. A similar pattern was seen on SSC15 for the QTL affecting ultimate pH in the 2 muscles and drip loss. The results from this study will be helpful for fine mapping and identifying genes affecting meat quality traits, and tightly linked markers may be incorporated into marker-assisted selection programs

Udgivelsesdato: Jan Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype variants, have been demonstrated to modify the disease course of rheumatoid arthritis (RA). Surfactant protein D (SP-D) shares important structural and functional properties with MBL suggesting that SP-D may be an additional RA disease modifier. The Met11Thr polymorphism in the N-terminal part of SP-D is an important determinant for the SP-D serum level, but this polymorphism is also essential to the function and assembly into oligomers. We aimed to compare the serum levels of SP-D in a cohort of newly diagnosed untreated RA patients with healthy matched controls, and to investigate if there was an association to core measures of disease activity within the first year after disease onset. Secondly, we aimed to investigate whether the Met11Thr polymorphism was associated with RA. Serum SP-D was significantly lower in DMARD naive RA patients compared with healthy controls (P = 0.016). Median SP-D concentration at inclusion was 878 ng/ml (95% CI: 730-1033) and 1164 ng/ml (95% CI: 1093-1366) in RA patients and matched controls, respectively. SP-D increased during Methotrexate treatment (P < 0.0001), and at 1-year follow-up median SP-D was 1032 ng/ml (95% CI: 777-1255). SP-D levels did not correlate with traditional disease activity measures. The Thr11/Thr11 genotype and the Thr11 allele tended to be more frequent in RA patients. In conclusion, the low serum level of SP-D and the lack of correlation with traditional disease activity measures indicate that SP-D reflects a distinctive aspect in the RA pathogenesis.

To investigate the congenital complex vertebral malformation syndrome (CVM) in Holstein calves, two breeding studies were performed including 262 and 363 cows, respectively. Cows were selected from the Danish Cattle Database based on pedigree and insemination records. Selected cows were progeny of sires with an established heterozygous CVM genotype and pregnant after insemination with semen from another sire with heterozygous CVM genotype. Following calving the breeders should state, if the calf was normal and was requested to submit dead calves for necropsy. In both studies, significantly fewer CVM affected calves than expected were obtained; a finding probably reflecting extensive intrauterine mortality in CVM affected foetuses. The findings illustrate increased intrauterine mortality as a major potential bias in observational studies of inherited disorders.