Acquisition of a Distributed Computation and Immersive Visualization Environment for Complex Systems - Scientific Applications on Arrays of Multiprocessors (SCAAMP)

NSF Award ID: CDA-9601632 9/15/1996-8/31/199

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

‘Bombed into stardom!’: Roddy McDowall, ‘British evacuee star’ in Hollywood

This article considers the beginnings of the British actor Roddy McDowall's career as a child star in Hollywood. Following his relocation to the United States in October 1940 and signing a contract with Twentieth Century-Fox, McDowall quickly became one of Hollywood's most popular juvenile actors. For the duration of the Second World War, McDowall's star image was indissoluble from his status as a war guest: he was ‘a British evacuee star’. McDowall thus became an unofficial ambassador for the British nation, much like his fellow evacuees, who were widely recognised for their work improving Anglo-American relations. In the management of McDowall's image, and in his screen performances, there is a discernible effort to substantiate certain attitudes about the character and attributes of the British nation but also to challenge certain prejudices about English sissy boys. McDowall's star text was carefully managed so that the image of the actor presented by the media and the fictional characters he played on screen congealed in a productive way to inspire among American audiences specific sentiments about the British and America's relationship with the British nation during wartime. Analysing the representation of McDowall in American film magazines during the early 1940s, as well as his performances in three war-themed productions – Confirm or Deny (1941), On the Sunny Side (1942) and The White Cliffs of Dover (1944) – I explore the ways McDowall's star text functioned in its geopolitical and bio-political contexts