BackgroundThe dissection of complex traits of economic importance to the pig industry requires the availability of a significant number of genetic markers, such as single nucleotide polymorphisms (SNPs). This study was conducted to discover several hundreds of thousands of porcine SNPs using next generation sequencing technologies and use these SNPs, as well as others from different public sources, to design a high-density SNP genotyping assay.Methodology/Principal FindingsA total of 19 reduced representation libraries derived from four swine breeds (Duroc, Landrace, Large White, Pietrain) and a Wild Boar population and three restriction enzymes (AluI, HaeIII and MspI) were sequenced using Illumina's Genome Analyzer (GA). The SNP discovery effort resulted in the de novo identification of over 372K SNPs. More than 549K SNPs were used to design the Illumina Porcine 60K+SNP iSelect Beadchip, now commercially available as the PorcineSNP60. A total of 64,232 SNPs were included on the Beadchip. Results from genotyping the 158 individuals used for sequencing showed a high overall SNP call rate (97.5%). Of the 62,621 loci that could be reliably scored, 58,994 were polymorphic yielding a SNP conversion success rate of 94%. The average minor allele frequency (MAF) for all scorable SNPs was 0.274.Conclusions/SignificanceOverall, the results of this study indicate the utility of using next generation sequencing technologies to identify large numbers of reliable SNPs. In addition, the validation of the PorcineSNP60 Beadchip demonstrated that the assay is an excellent tool that will likely be used in a variety of future studies in pigs.
IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease.
Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or ;1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.
Testosterone replacement in hypogonadal men improves body composition, mood, and sexual functioning. In this 90-d study, we compared the pharmacokinetics and treatment effectiveness of a topical testosterone gel (AA2500) at two concentrations, 50 mg/d and 100 mg/d, to a testosterone patch and placebo gel in 406 hypogonadal men. Pharmacokinetic profiles were obtained, body composition was measured, and mood and sexual function were monitored. AA2500 treatments resulted in dose-dependent improvements in all pharmacokinetic parameters, compared with testosterone patch and placebo. Mean average concentrations at d 90 T were 13.8, 17.1, 11.9, and 7.3 nmol/liter for 50 mg/d AA2500, 100 mg/d AA2500, testosterone patch, and placebo, respectively. At d 90, the 100 mg/d AA2500 treatment improved lean body mass by 1.7 kg and percentage of body fat by 1.2% to a significantly greater degree than either control treatment. Significant improvements in spontaneous erections, sexual desire, and sexual motivation were also evidenced with the 100 mg/d AA2500 dose in comparison with placebo. Testosterone gel was well tolerated; however, the testosterone patch resulted in a high rate of application site reactions. Overall, AA2500 is an effective, well tolerated treatment for hypogonadism.
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