Natural populations subjected to strong environmental selection pressures offer a window into the genetic underpinnings of evolutionary change. Cavefish populations, Astyanax mexicanus (Teleostei: ...Characiphysi), exhibit repeated, independent evolution for a variety of traits including eye degeneration, pigment loss, increased size and number of taste buds and mechanosensory organs, and shifts in many behavioural traits. Surface and cave forms are interfertile making this system amenable to genetic interrogation; however, lack of a reference genome has hampered efforts to identify genes responsible for changes in cave forms of A. mexicanus. Here we present the first de novo genome assembly for Astyanax mexicanus cavefish, contrast repeat elements to other teleost genomes, identify candidate genes underlying quantitative trait loci (QTL), and assay these candidate genes for potential functional and expression differences. We expect the cavefish genome to advance understanding of the evolutionary process, as well as, analogous human disease including retinal dysfunction.
Abstract
The Ensembl software resources are a stable infrastructure to store, access and manipulate genome assemblies and their functional annotations. The Ensembl ‘Core’ database and Application ...Programming Interface (API) was our first major piece of software infrastructure and remains at the centre of all of our genome resources. Since its initial design more than fifteen years ago, the number of publicly available genomic, transcriptomic and proteomic datasets has grown enormously, accelerated by continuous advances in DNA-sequencing technology. Initially intended to provide annotation for the reference human genome, we have extended our framework to support the genomes of all species as well as richer assembly models. Cross-referenced links to other informatics resources facilitate searching our database with a variety of popular identifiers such as UniProt and RefSeq. Our comprehensive and robust framework storing a large diversity of genome annotations in one location serves as a platform for other groups to generate and maintain their own tailored annotation. We welcome reuse and contributions: our databases and APIs are publicly available, all of our source code is released with a permissive Apache v2.0 licence at http://github.com/Ensembl and we have an active developer mailing list (http://www.ensembl.org/info/about/contact/index.html).
Database URL: http://www.ensembl.org
Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown ...or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we ...sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus ...sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ∼267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show ...that most algorithms are able to identify discrete transcript components with high success rates but that assembly of complete isoform structures poses a major challenge even when all constituent elements are identified. Expression-level estimates also varied widely across methods, even when based on similar transcript models. Consequently, the complexity of higher eukaryotic genomes imposes severe limitations on transcript recall and splice product discrimination that are likely to remain limiting factors for the analysis of current-generation RNA-seq data.
Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in ...lower vertebrates. The genetic mechanisms underlying the evolution of these elaborate traits are poorly understood. The platyfish, X. maculatus, offers a unique model to better understand the molecular biology of such traits. We report here the sequencing of the platyfish genome. Integrating genome assembly with extensive genetic maps identified an unexpected evolutionary stability of chromosomes in fish, in contrast to in mammals. Genes associated with viviparity show signatures of positive selection, identifying new putative functional domains and rare cases of parallel evolution. We also find that genes implicated in cognition show an unexpectedly high rate of duplicate gene retention after the teleost genome duplication event, suggesting a hypothesis for the evolution of the behavioral complexity in fish, which exceeds that found in amphibians and reptiles.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data ...from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
Community acquired pneumonia is a common condition that causes considerable morbidity and has a mortality rate of approximately 20% for patients admitted to hospital in the United Kingdom. 1 It is ...diagnosed in 5-12% of adults who present to general practitioners with symptoms of lower respiratory tract infection, 2 3 and 22-42% are subsequently admitted to hospital. 3 4 Adherence to previous guidelines has been poor, and this variation in practice can lead to suboptimal outcomes such as increased mortality and longer stay in hospital. 5 6 7 Hospital acquired pneumonia (excluding ventilator associated pneumonia) has a point prevalence of approximately 1% of hospital inpatients, is estimated to lengthen hospital admission by an average of eight days, and has a high mortality rate. 8 9 This article summarises the most recent recommendations for the management of both types of pneumonia from the National Institute for Health and Care Excellence (NICE). Confusion (abbreviated mental test score 8 or less or new disorientation in person, place, or time)* Raised blood urea nitrogen (over 7 mmol/L) Raised respiratory rate (30 breaths per minute or more) Low blood pressure (diastolic 60 mm Hg or less, or systolic less than 90 mm Hg) Age 65 years or more Patients are stratified for risk of death as follows: 0 or 1=low risk (less than 3% mortality risk) 2=intermediate risk (3 to 15% mortality risk) 3 to 5=high risk (more than 15% mortality risk) *For guidance on delirium, please refer to National Institute for Health and Care Excellence.
Triage and redirection of patients to alternative care providers is one tool used to overcome the growing issue of crowding in emergency departments (EDs). Electronic patient self-triage (eTriage) ...may reduce waiting times and required face-to-face contact. There are limited studies into its efficacy, accuracy and validity in an ED setting.
The aim of this study was to assess the agreement and validity of eTriage with a reference standard of nurse face-to-face triage. A secondary aim was to assess the ability of both systems to predict high and low acuity outcomes.
This was a retrospective study conducted over 8 months in two UK hospitals. Inclusion criteria were all ambulatory patients aged ≥18. All patients completed an eTriage and nurse-led triage using the Manchester Triage System (MTS).
During the study period, 43 788 adult patients attended one of the two ED sites and 26 757 used eTriage. A total of 1424 patient episodes had no recorded MTS and were excluded from the study leaving 25 333 paired triages for the final cohort. Agreement between eTriage and nurse triage was low with a weighted Kappa coefficient of 0.14 (95% CI, 0.14-0.15) with an associated weak positive correlation (rs 0.321). Level of undertriage by eTriage compared with nurse triage was 10.1%, and overtriage was 59.2%. The sensitivity for prediction of high acuity outcomes was 88.5% (95% CI, 77.9-95.3%) for eTriage and 53.8% (95% CI 41.1-66.0%) for nurse MTS. The specificity for predicting low risk patients was 88.5% (95% CI, 87.4-89.5%) for eTriage and 80.6% (95% CI, 79.3-81.8%) for nurse MTS.
Agreement and correlation of eTriage with the reference standard of nurse MTS was low; patients using eTriage tended to over triage when compared to the triage nurse. eTriage had a higher sensitivity for high acuity presentations and demonstrated similar specificity for low acuity presentations when compared to triage nurse MTS. Further work is necessary to validate eTriage as a potential tool for safe redirection of ED attenders to alternative care providers.
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