Ensembl 2024.

Ensembl (https://www.ensembl.org) is a freely available genomic resource that has produced high-quality annotations, tools, and services for vertebrates and model organisms for more than two decades. In recent years, there has been a dramatic shift in the genomic landscape, with a large increase in the number and phylogenetic breadth of high-quality reference genomes, alongside major advances in the pan-genome representations of higher species. In order to support these efforts and accelerate downstream research, Ensembl continues to focus on scaling for the rapid annotation of new genome assemblies, developing new methods for comparative analysis, and expanding the depth and quality of our genome annotations. This year we have continued our expansion to support global biodiversity research, doubling the number of annotated genomes we support on our Rapid Release site to over 1700, driven by our close collaboration with biodiversity projects such as Darwin Tree of Life. We have also strengthened support for key agricultural species, including the first regulatory builds for farmed animals, and have updated key tools and resources that support the global scientific community, notably the Ensembl Variant Effect Predictor. Ensembl data, software, and tools are freely available.

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Ensembl 2023.

Ensembl (https://www.ensembl.org) has produced high-quality genomic resources for vertebrates and model organisms for more than twenty years. During that time, our resources, services and tools have continually evolved in line with both the publicly available genome data and the downstream research and applications that utilise the Ensembl platform. In recent years we have witnessed a dramatic shift in the genomic landscape. There has been a large increase in the number of high-quality reference genomes through global biodiversity initiatives. In parallel, there have been major advances towards pangenome representations of higher species, where many alternative genome assemblies representing different breeds, cultivars, strains and haplotypes are now available. In order to support these efforts and accelerate downstream research, it is our goal at Ensembl to create high-quality annotations, tools and services for species across the tree of life. Here, we report our resources for popular reference genomes, the dramatic growth of our annotations (including haplotypes from the first human pangenome graphs), updates to the Ensembl Variant Effect Predictor (VEP), interactive protein structure predictions from AlphaFold DB, and the beta release of our new website.

Ensembl 2022.

Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.

Ensembl 2021.

The Ensembl project (https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release (http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser (https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.

Ensembl 2020.

The Ensembl (https://www.ensembl.org) is a system for generating and distributing genome annotation such as genes, variation, regulation and comparative genomics across the vertebrate subphylum and key model organisms. The Ensembl annotation pipeline is capable of integrating experimental and reference data from multiple providers into a single integrated resource. Here, we present 94 newly annotated and re-annotated genomes, bringing the total number of genomes offered by Ensembl to 227. This represents the single largest expansion of the resource since its inception. We also detail our continued efforts to improve human annotation, developments in our epigenome analysis and display, a new tool for imputing causal genes from genome-wide association studies and visualisation of variation within a 3D protein model. Finally, we present information on our new website. Both software and data are made available without restriction via our website, online tools platform and programmatic interfaces (available under an Apache 2.0 license) and data updates made available four times a year.

Discovery of high-confidence human protein-coding genes and exons by whole-genome PhyloCSF helps elucidate 118 GWAS loci.

The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present the first whole-genome PhyloCSF prediction tracks for human, mouse, chicken, fly, worm, and mosquito. We develop a workflow that uses machine learning to predict novel conserved protein-coding regions and efficiently guide their manual curation. We analyze more than 1000 high-scoring human PhyloCSF regions and confidently add 144 conserved protein-coding genes to the GENCODE gene set, as well as additional coding regions within 236 previously annotated protein-coding genes, and 169 pseudogenes, most of them disabled after primates diverged. The majority of these represent new discoveries, including 70 previously undetected protein-coding genes. The novel coding genes are additionally supported by single-nucleotide variant evidence indicative of continued purifying selection in the human lineage, coding-exon splicing evidence from new GENCODE transcripts using next-generation transcriptomic data sets, and mass spectrometry evidence of translation for several new genes. Our discoveries required simultaneous comparative annotation of other vertebrate genomes, which we show is essential to remove spurious ORFs and to distinguish coding from pseudogene regions. Our new coding regions help elucidate disease-associated regions by revealing that 118 GWAS variants previously thought to be noncoding are in fact protein altering. Altogether, our PhyloCSF data sets and algorithms will help researchers seeking to interpret these genomes, while our new annotations present exciting loci for further experimental characterization.

Ensembl 2019.

The Ensembl project (https://www.ensembl.org) makes key genomic data sets available to the entire scientific community without restrictions. Ensembl seeks to be a fundamental resource driving scientific progress by creating, maintaining and updating reference genome annotation and comparative genomics resources. This year we describe our new and expanded gene, variant and comparative annotation capabilities, which led to a 50% increase in the number of vertebrate genomes we support. We have also doubled the number of available human variants and added regulatory regions for many mouse cell types and developmental stages. Our data sets and tools are available via the Ensembl website as well as a through a RESTful webservice, Perl application programming interface and as data files for download.

What Do Patients with Chronic Spinal Pain Expect from Their Physiotherapist?

Purpose: Evidence has suggested that patients' expectations influence the clinical course when they present with low back pain (LBP). However, little empirical evidence has outlined the nature of these expectations. The aim of this study was to describe LBP patients' expectations of physiotherapy. Method: Seventy-nine adult patients who had LBP for more than 16 weeks and were referred for physiotherapy at two hospital physiotherapy departments in St. John's, Newfoundland and Labrador, were included. They filled out a questionnaire detailing their expectations of treatment. Results: Before treatment, more than 90% of patients expected a physical examination, tests or investigations, a diagnosis, reassurance and advice, and clear explanations of causation, symptom management, and benefits and risks of treatment. Approximately half hoped for a prescription or referral to a specialist, and about 60% hoped to discuss problems in their life. Conclusions: The findings of this study indicate that patients attend physiotherapy with clear expectations about what information should be provided. Most expected tests or investigations leading to diagnosis and an explanation of causation; this presents a challenge for clinicians, given the current understanding of LBP reflected in international practice guidelines. The fact that more than half of the patients wanted to discuss problems in their life points to the need for physiotherapists to consider LBP from a bio-psychosocial perspective.

Objectif : selon certaines données probantes, les attentes des patients influencent l'évolution clinique lorsqu'ils consultent pour des douleurs lombaires (DL). Cependant, peu de données empiriques exposent la nature de ces attentes. La présente étude visait à décrire les attentes des patients ayant des DL vis-à-vis de la physiothérapie. Méthodologie : au total, 79 patients adultes atteints de DL depuis plus de 16 semaines, qui avaient été dirigés vers l'un des deux départements de physiothérapie des hôpitaux de St. John's, à Terre-Neuve-et-Labrador, ont participé à l'étude. Ils ont rempli un questionnaire détaillant leurs attentes en matière de traitement. Résultats : avant le traitement, plus de 90 % des patients s'attendaient à subir un examen physique, des tests ou des investigations et à recevoir un diagnostic, des paroles rassurantes et des conseils ainsi que des explications claires sur la cause de leur douleur, la prise en charge des symptômes et les avantages ou les risques du traitement. Environ la moitié espérait recevoir une prescription ou être dirigée vers un spécialiste, et environ 60 % souhaitaient parler de leurs problèmes personnels. Conclusion : d'après les résultats de cette étude, les patients ont des attentes claires quant à l'information qu'ils devraient recevoir en physiothérapie. La majorité s'attendent à subir des tests ou des examens qui permettront de poser un diagnostic et d'expliquer la cause de leurs problèmes. Compte tenu des connaissances des DL énoncées dans les lignes de pratique internationales, c'est un défi pour les cliniciens. Puisque plus de la moitié des patients souhaitaient parler de leurs problèmes personnels, les physiothérapeutes devraient aborder les DL d'un point de vue biopsychosocial.

Consensus coding sequence (CCDS) database: a standardized set of human and mouse protein-coding regions supported by expert curation.

The Consensus Coding Sequence (CCDS) project provides a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assembly in genome annotations produced independently by NCBI and the Ensembl group at EMBL-EBI. This dataset is the product of an international collaboration that includes NCBI, Ensembl, HUGO Gene Nomenclature Committee, Mouse Genome Informatics and University of California, Santa Cruz. Identically annotated coding regions, which are generated using an automated pipeline and pass multiple quality assurance checks, are assigned a stable and tracked identifier (CCDS ID). Additionally, coordinated manual review by expert curators from the CCDS collaboration helps in maintaining the integrity and high quality of the dataset. The CCDS data are available through an interactive web page (https://www.ncbi.nlm.nih.gov/CCDS/CcdsBrowse.cgi) and an FTP site (ftp://ftp.ncbi.nlm.nih.gov/pub/CCDS/). In this paper, we outline the ongoing work, growth and stability of the CCDS dataset and provide updates on new collaboration members and new features added to the CCDS user interface. We also present expert curation scenarios, with specific examples highlighting the importance of an accurate reference genome assembly and the crucial role played by input from the research community.

Current status and new features of the Consensus Coding Sequence database.

The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets.

Structural and functional annotation of the porcine immunome.

BACKGROUND: The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems. RESULTS: The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome. CONCLUSIONS: This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig's adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.

GENCODE: the reference human genome annotation for The ENCODE Project.

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

A systematic survey of loss-of-function variants in human protein-coding genes.

Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.

Trauma management incorporating focused assessment with computed tomography in trauma (FACTT) - potential effect on survival.

BACKGROUND: Immediate recognition of life-threatening conditions and injuries is the key to trauma management. To date, the impact of focused assessment with computed tomography in trauma (FACTT) has not been formally assessed. We aimed to find out whether the concept of using FACTT during primary trauma survey has a negative or positive effect on survival. METHODS: In a retrospective, multicentre study, we compared our time management and probability of survival (Ps) in major trauma patients who received FACTT during trauma resuscitation with the trauma registry of the German Trauma Society (DGU). FACTT is defined as whole-body computed tomography (WBCT) during primary trauma survey. We determined the probability of survival according to the Trauma and Injury Severity Score (TRISS), the Revised Injury Severity Classification score (RISC) and the standardized mortality ratio (SMR). RESULTS: We analysed 4.817 patients from the DGU database from 2002 until 2004, 160 (3.3%) were from our trauma centre at the Ludwig-Maximilians-University (LMU) and 4.657 (96.7%) from the DGU group. 73.2% were male with a mean age of 42.5 years, a mean ISS of 29.8. 96.2% had suffered from blunt trauma. Time from admission to FAST (focused assessment with sonography for trauma)(4.3 vs. 8.7 min), chest x-ray (8.1 vs. 16.0 min) and whole-body CT (20.7 vs. 36.6 min) was shorter at the LMU compared to the other trauma centres (p < 0.001). SMR calculated by TRISS was 0.74 (CI95% 0.40-1.08) for the LMU (p = 0.24) and 0.92 (CI95% 0.84-1.01) for the DGU group (p = 0.10). RISC methodology revealed a SMR of 0.69 (95%CI 0.47-0.92) for the LMU (p = 0.043) and 1.00 (95%CI 0.94-1.06) for the DGU group (p = 0.88). CONCLUSION: Trauma management incorporating FACTT enhances a rapid response to life-threatening problems and enables a comprehensive assessment of the severity of each relevant injury. Due to its speed and accuracy, FACTT during primary trauma survey supports rapid decision-making and may increase survival.

Emergency chest tube placement in trauma care - which approach is preferable?

BACKGROUND: Pneumothorax is present in about 20% of blunt major trauma cases. Insertion of an intercostal tube drainage is one effective treatment, however it is unclear whether the thoracostomy has more advantages if placed in the ventral (2.-3. intercostal space) or lateral (4.-6. intercostal space) approach. The aim of this study was to determine, whether there are any differences between the two approaches in respect of malposition and complications. MATERIAL AND METHODS: The data from 851 consecutive patients, admitted to our trauma centre from January 2000 to June 2004, was collected and analysed prospectively. The inclusion criteria were: ISS > or = 16, insertion of an intercostal tube and subsequent thoracic computed tomography. Epidemiological and physiological data were analysed together with the location of the tube (ventral or lateral). The attending physician was free to choose the location of insertion. Chest tubes placed both on-scene and in-hospital chest tubes were investigated. Malpositions, defined as extrathoracic, abdominal, parenchymal or interlobal positions, were analysed by reviewing the computed tomography of the thorax (CT). Complications, like injuries to vessels or organs, infection or empyaema were analysed using our standardised prospective trauma protocol. Furthermore, the rate of clinically relevant malfunctions due to malposition was investigated as well as the number of chest tubes that had to be replaced. RESULTS: One hundred and one chest tubes were inserted in 68 patients with multiple trauma (mean age 40.7, ISS=38.1, AIS thorax=3.9). In 21 cases a ventral approach was chosen (20.8%) and in 80 a lateral approach (79.2%). CT revealed malposition in two of the ventrally placed tubes (9.5%) and in 20 of the laterally placed tubes (25%) (p=0.15, Fisher's exact test). One tube was identified in a subcutaneous location 17 chest tubes, after ventral approach all of them as a result of lateral approaches, were placed in the interlobe. No interlobal positions were observed in the ventral group. The interlobal position was found to be significantly higher in the lateral approach (p=0.013, Fisher's exact test). Clinically relevant malfunction was diagnosed in 6 of the 22 malpositioned chest tubes (5.9%). These tubes had to be repositioned, one was placed ventrally, the other five were placed laterally. CONCLUSIONS: In our setting physicians preferred the lateral approach on-scene as well as in-hospital. In every fifth patient malpositioning of the tube was observed, mostly interlobal after lateral chest tube, however only few were associated with relevant clinical malfunctions. The probability of interlobal malpositioning is significantly higher when using the lateral approach as opposed to the ventral approach. Correction of malpositioned and ineffective chest tubes was necessary in every 17th case. No statistically significant difference between the two approaches for functional malposition was observed. Hence both approaches for emergency chest tube insertion seem to be equally justified.

Susceptibility of automated external defibrillators to train overhead lines and metro third rails.

INTRODUCTION: Immediate accessibility to automated external defibrillators (AED) is recommended for highly frequented public areas. In train terminals and metro stations electromagnetic interference (EMI) is present. In preparation for a public access defibrillation (PAD) programme in this environment possible effects on AED safety and accuracy were studied. METHODS: In typical public transportation settings 11 different AED models were bench tested for their sensitivity and specificity of ECG analysis with shockable and nonshockable rhythms provided by an ECG simulator. The devices were exposed to the electromagnetic interference of a rail system operating with 15 kV alternating current (ac) with a frequency of 16 2/3 Hz and a subway system powered with 750 V direct current (dc). AED cables were setup parallel and perpendicular to the tracks, the tests were carried out at 3 m distance from the rails in an empty station and with incoming trains. RESULTS: A total of 5280 tests were recorded, each device was tested a total of 480 times. Fifteen kilovolts 16 2/3 Hz ac interfered more than 750 V dc with the tachyarrhythmia detection systems (P < 0.0001). An AED setup with electrode cables perpendicular to track and power line reduced interference (P < 0.0001), while incoming trains had no significant effect on ECG analysis (P = 0.19). Depending on the AED model, sensitivity ranged from 60 to 100% and specificity from 54 to 100%, representing a positive likelihood-ratio from 1.3 to 241 and a negative likelihood-ratio from 0.7 to 0.0. In the public transportation setting tested, four AED models were unsuitable for automated defibrillation as these devices demonstrated an unacceptable performance in respect of accuracy and safety. In the train setting two devices performed with an accuracy of 57 and 65%. One AED recommended shocks for sinus rhythm at normal frequency. In the metro setting one AED did not advise shocks for ventricular tachycardia. CONCLUSION: Shock advisory systems of some AED models are susceptible to electromagnetic interference, especially in terminals with 15 kV 16 2/3 Hz ac power supplies. Interference is minimized, if patient position is parallel and electrode cables are perpendicular to overhead line. The choice of AED model for train or metro stations depends on its lack of susceptibility to typical electromagnetic interference.

Effect of digital cellular phones on tachyarrhythmia analysis of automated external defibrillators.

OBJECTIVES: Emergency services personnel, family members, laypersons or patients often carry and use mobile phones on sites of emergencies. As there are reported effects on implanted pacemakers and cardioverter defibrillators, the influence of digital cellular phones on automated external defibrillators was studied. METHODS: Twelve automated external defibrillator models were bench tested for their correct decision to or not to advise a shock, while being exposed to electromagnetic interference from a handheld cellular phone with 2 W or a portable cellular phone with 8 W transmitting power. The phones were programmed by a special subscriber identity module card to maximum output power with a carrier frequency of 906.2 MHz. The tests were conducted with a burst frequency of 217 Hz in speech mode and 2-8 Hz in discontinuous transmitting exchange mode. The sensitivity and specificity of electrocardiogram analysis systems were tested, with shockable and non-shockable rhythms provided by an electrocardiogram simulator and on two human subjects with normal sinus rhythm. RESULTS: A total of 8640 tests were recorded, each automated external defibrillator was tested a total of 720 times. The automated external defibrillators demonstrated a sensitivity of 100% and a specificity of 100%, representing a positive likelihood ratio of 8641 and a negative likelihood ratio of 0.000. In this setting all automated external defibrillators analysed correctly even under worst-case testing conditions, and performed excellently without any single failure. In some devices, voice prompts were distorted beyond comprehension, as the coil of the automated external defibrillator speaker received the pulsed signals. CONCLUSION: Shock advisory systems of automated external defibrillators are not susceptible to electromagnetic interference of 900 MHz cellular phones. Voice prompts, however, could be distorted by the operation of nearby digital mobile phones. During automated external defibrillator training this issue needs to be addressed.

The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism.

The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99-100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters.