The political and administrative career of Sir Henry Vane the Younger 1640 to April 1653

This thesis covers the period (1640-53) of Vane's significant political activity in England. It examines his work as administrator -a neglected aspect of his career. The fluctuating fortunes and membership of the group led by Vane and St. John are traced; its struggle with Holies's group was reflected in the use made of the Committee of Both Kingdoms to deprive parliament as a whole of authority. Vane's mastery of parliamentary tactics was often demonstrated, for instance in the Self-Denying Ordinance, which had important political purposes. His support of religious toleration in England, Ireland and America contrasts strongly with his harsh attitude to political opposition. By December 1646 Holles's group dominated the Commons, and Vane virtually boycotted parliament for some months. Though always aware of the dangers of military control, he was at one with some Army leaders, though not with the Levellers, on many issues, and when the Army intervened in 1647 he returned to the House. His administrative gifts were shown by his work on the Committee of Both Kingdoms, and as Navy Treasurer; the financial rewards of the latter office were considerable from 1645 onwards. His withdrawal from public affairs in January 1649 was followed by a period of extraordinary activity, in which Vane was the architect of the Union with Scotland, the abortive Union with Holland, and above all, the Commonwealth Navy, though he did not neglect the interests of his constituency, his family or himself. He probably opposed the Dutch War at first, but in December 1652 he wrested from a reluctant parliament authority for an Admiralty Commission, whose new policy bore fruit in Blake's victory off Portland. By this time Vane was politically isolated, and at odds with Hesilrige and Marten; friction with Cromwell on naval policy was followed by the dismissal of the Rump.<p

Genomic prediction in a multiploid crop: genotype by environment interaction and allele dosage effects on predictive ability in banana

Open Access Journal; Published online: 2 March 2018Improving the efficiency of selection in conventional crossbreeding is a major priority in banana (Musa spp.) breeding. Routine application of classical marker assisted selection (MAS) is lagging in banana due to limitations in MAS tools. Genomic selection (GS) based on genomic prediction models can address some limitations of classical MAS, but the use of GS in banana has not been reported to date. The aim of this study was to evaluate the predictive ability of six genomic prediction models for 15 traits in a multi-ploidy training population. The population consisted of 307 banana genotypes phenotyped under low and high input field management conditions for two crop cycles. The single nucleotide polymorphism (SNP) markers used to fit the models were obtained from genotyping by sequencing (GBS) data. Models that account for additive genetic effects provided better predictions with 12 out of 15 traits. The performance of BayesB model was superior to other models particularly on fruit filling and fruit bunch traits. Models that included averaged environment data were more robust in trait prediction even with a reduced number of markers. Accounting for allele dosage in SNP markers (AD-SNP) reduced predictive ability relative to traditional bi-allelic SNP (BA-SNP), but the prediction trend remained the same across traits. The high predictive values (0.47– 0.75) of fruit filling and fruit bunch traits show the potential of genomic prediction to increase selection efficiency in banana breeding

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Multiple loci on 8q24 associated with prostate cancer susceptibility

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we have previously conducted a genome-wide association study in which 541, 129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and 1,894 controls. We have now evaluated promising associations in a second stage, in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls, and a third stage, involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to previously identified loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11, and 22 (P=1.6×10−8 to P=2.7×10−33)