18 research outputs found
Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.
An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data
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
Taxonomic review of the orders mysida and stygiomysida (Crustacea, Peracarida)
The order Mysida (2 families, 178 genera, 1132 species) contains species across a broad range of habitats, such as subterranean, fresh, brackish, coastal, and surface to deep-sea habitats. The Stygiomysida (2 families, 2 genera, 16 species), however, are found primarily in subterranean waters, but always in waters with a marine influence. The Mysida and Stygiomysida body is divided into three main regions: cephalon, thorax, and abdomen. They are shrimp-like in appearance, containing morphological features earlier referred to as defining a "caridoid facies". The shrimp-like morphology was to some extent diagnostic for the historic Decapod taxon Schizopoda, containing the Nebalia, Mysida, Lophogastrida, and Euphausiacea. In 1904 the concept of Schizopoda was abandoned, and the Mysidacea (Mysida and Lophogastrida) along with Cumacea, Amphipoda, Isopoda, and Tanaidacea were placed in a new taxon, the Peracarida. Later discoveries of groundwater mysids led to the establishment of Stygiomysida, but placement to either Lophogastrida or Mysida remained unclear. The presence of oostegites and absence of podobranchiae, coupled with non-statocyst bearing uropods have been used to classify the Stygiomysida as a primitive Mysida family, comparable to Petalophthalmidae. On the other hand, equally suggestive characters, but for a Lophogastrida affiliation, was suggested for the archaic foregut characters and again, non-statocyst bearing uropods. With the inclusion of DNA sequence data of ribosomal genes, sister group relationships between Stygiomysida, Lophogastrida, and Mictacea within the Peracarida are observed, which supports a classification of the Stygiomysida as a separate order removed from the Mysida