Publications by authors named "Claire Davidson"

19 Publications

  • Page 1 of 1

Ensembl 2021.

Nucleic Acids Res 2021 01;49(D1):D884-D891

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkaa942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778975PMC
January 2021

Expert curation of the human and mouse olfactory receptor gene repertoires identifies conserved coding regions split across two exons.

BMC Genomics 2020 Mar 3;21(1):196. Epub 2020 Mar 3.

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.

Background: Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with 874 in human and 1483 loci in mouse (including pseudogenes). The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences.

Results: Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

Conclusions: This work provides the most comprehensive curation effort of the human and mouse OR gene repertoires to date. The complete annotation has been integrated into the GENCODE reference gene set, for immediate availability to the research community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-020-6583-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055050PMC
March 2020

Ensembl 2020.

Nucleic Acids Res 2020 01;48(D1):D682-D688

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkz966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145704PMC
January 2020

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

Genome Res 2019 12 19;29(12):2073-2087. Epub 2019 Sep 19.

MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.246462.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886504PMC
December 2019

Ensembl 2019.

Nucleic Acids Res 2019 01;47(D1):D745-D751

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gky1113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323964PMC
January 2019

Correction: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.

Genet Med 2019 Aug;21(8):1897-1898

APHP, Service de genetique medicale, Necker- Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-018-0327-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608434PMC
August 2019

IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.

Genet Med 2019 04 12;21(4):837-849. Epub 2018 Sep 12.

APHP, Service de genetique medicale, Necker-Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France.

Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.

Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms.

Results: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments.

Conclusion: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-018-0268-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752297PMC
April 2019

Development and Examination of the Reactive Attachment Disorder and Disinhibited Social Engagement Disorder Assessment Interview.

Assessment 2020 06 2;27(4):749-765. Epub 2018 Sep 2.

Adverse Childhood Experiences Clinical and Research Centre, Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK.

The fifth edition of the () categorizes reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) as two separate disorders, and their criteria are revised. For DSED, the core symptoms focus on abnormal social disinhibition, and symptoms regarding lack of selective attachment have been removed. The core symptoms of RAD are the absence of attachment behaviors and emotional dysregulation. In this study, an international team of researchers modified the Child and Adolescent Psychiatric Assessment for RAD to update it from to criteria for RAD and DSED. We renamed the interview the eactive attachment disorder nd isinhibited social engagement disorder ssessment (RADA). Foster parents of 320 young people aged 11 to 17 years completed the RADA online. Confirmatory factor analysis of RADA items identified good fit for a three-factor model, with one factor comprising DSED items (indiscriminate behaviors with strangers) and two factors comprising RAD items (RAD1: failure to seek/accept comfort, and RAD2: withdrawal/hypervigilance). The three factors showed differential associations with clinical symptoms of emotional and social impairment. Time in foster care was not associated with scores on RAD1, RAD2, or DSED. Higher age was associated with lower scores on DSED, and higher scores on RAD1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1073191118797422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227130PMC
June 2020

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

Nucleic Acids Res 2018 01;46(D1):D221-D228

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkx1031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753299PMC
January 2018

Association between Reactive Attachment Disorder/Disinhibited Social Engagement Disorder and Emerging Personality Disorder: A Feasibility Study.

ScientificWorldJournal 2016 6;2016:5730104. Epub 2016 Jun 6.

University of Glasgow, Health and Wellbeing, Caledonian House, Royal Hospital for Sick Children, Glasgow G3 8SJ, UK.

A systematic review of reactive attachment disorder (RAD)/disinhibited social engagement disorder (DSED) in adolescence highlighted that young people with the disorder had indiscriminate friendliness with difficulties in establishing and maintaining stable relationships. Most reported experiences of rejection. We were struck by similarities between the above and features of emergence of personality disorders (EPD). This feasibility study aimed to determine best ways of recruiting and retaining vulnerable young people and the proportion of participants with RAD/DSED who might have emerging borderline personality disorder (EBPD). Participants were referred to the study by their treating clinicians from local mental health teams. Results showed strong association between RAD/DSED and EBPD. Participant characteristics showed high levels of out of home placements, early termination of school careers, suicide attempts, quasipsychotic symptoms, and multiagency involvements. They experienced the project as an opportunity to talk about relationships and reported that they would like more of this in usual clinical contacts. They all agreed to be contacted for future studies. Previous studies have shown that early detection and treatment of emergent personality traits can alter trajectory. Future research will continue to explore these trajectories, explore detection of vulnerability factors, and evaluate interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/5730104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913055PMC
November 2017

Challenges of Assessing Maltreated Children Coming into Foster Care.

ScientificWorldJournal 2016 6;2016:5986835. Epub 2016 Jan 6.

Institute of Health and Wellbeing College of Medical, Veterinary and Life Sciences Academic Unit of Mental Health & Wellbeing, University of Glasgow Caledonia House Royal Hospital for Sick Children Yorkhill, Glasgow G3 8SJ, UK.

Children who have experienced early adversity have been known to be at risk of developing cognitive, attachment, and mental health problems; therefore, it is crucial that children entering foster care can be properly assessed as early as possible. There are known difficulties in assessing children in foster care, for example, in finding a reliable informant. An ongoing randomised controlled trial in Glasgow, Scotland, recruiting infants entering foster care, provides a unique opportunity to explore some of the issues which need to be considered when assessing these children. The assessment data of 70 infants entering care is described while exploring the reliability of foster carers as informants and the importance of infant engagement with tasks. This group of infants was shown to be having more problems than children from the general population. While correlations were found between a carer's level of concern about a child and the severity of a child's problem, there were still a number of children displaying worrying problem scores whom foster carers did not report concern. The child's engagement in the cognitive task showed associations with the child's attainment on the task. Findings emphasise the importance of a holistic assessment for these children and all should be considered as potential cases with Maltreatment-Associated Psychiatric Problems (MAPP).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/5986835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736566PMC
November 2016

Social relationship difficulties in autism and reactive attachment disorder: Improving diagnostic validity through structured assessment.

Res Dev Disabil 2015 May 6;40:63-72. Epub 2015 Mar 6.

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

Background: Autism Spectrum Disorder (ASD) versus Reactive Attachment Disorder (RAD) is a common diagnostic challenge for clinicians due to overlapping difficulties with social relationships. RAD is associated with neglect or maltreatment whereas ASD is not: accurate differential diagnosis is therefore critical. Very little research has investigated the relationship between the two, and it is unknown if standardised measures are able to discriminate between ASD and RAD. The current study aimed to address these issues.

Methods: Fifty eight children with ASD, and no history of maltreatment, were group matched on age with 67 children with RAD. Group profiles on multi-informant measures of RAD were investigated and group differences explored. Discriminant function analysis determined assessment features that best discriminated between the two groups.

Results: Although, according to parent report, children with ASD presented with significantly fewer indiscriminate friendliness behaviours compared to the RAD group (p<0.001), 36 children with ASD appeared to meet core RAD criteria. However, structured observation clearly demonstrated that features were indicative of ASD and not RAD for all but 1 of these 36 children.

Conclusions: Children with RAD and children with ASD may demonstrate similar social relationship difficulties but there appears to be a difference in the social quality of the interactions between the groups. In most cases it was possible to differentiate between children with ASD and children with RAD via structured observation. Nevertheless, for a small proportion of children with ASD, particularly those whose difficulties may be more subtle, our current standardised measures, including structured observation, may not be effective in differentiating RAD from ASD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ridd.2015.01.007DOI Listing
May 2015

Reactive attachment disorder in the general population: a hidden ESSENCE disorder.

ScientificWorldJournal 2013 18;2013:818157. Epub 2013 Apr 18.

Academic Unit of Mental Health & Wellbeing, University of Glasgow, Caledonia House, Royal Hospital for Sick Children, Glasgow G3 8SJ, UK.

Reactive attachment disorder (RAD) is a severe disorder of social functioning. Previous research has shown that children with RAD may have poor cognitive and language abilities; however, findings mainly come from biased, institutionalised samples. This paper describes the characteristics of all children who were given a suspected or likely diagnosis of reactive attachment disorder in an epidemiological study of approximately 1,600 children investigating the prevalence of RAD in the general population. We found that children with RAD are more likely to have multiple comorbidities with other disorders, lower IQs than population norms, more disorganised attachment, more problem behaviours, and poorer social skills than would be found in the general population and therefore have a complex presentation than can be described as ESSENCE. We discuss the clinical and educational implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/818157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654285PMC
September 2013

Prevalence of reactive attachment disorder in a deprived population.

Br J Psychiatry 2013 May 11;202(5):342-6. Epub 2013 Apr 11.

Institute of Mental Health & Wellbeing, University of Glasgow, UK.

Background: Reactive attachment disorder (RAD) is associated with early childhood maltreatment and has unknown population prevalence beyond infancy.

Aims: To estimate RAD prevalence in a deprived population of children.

Method: All 1646 children aged 6-8 years old in a deprived sector of an urban UK centre were screened for RAD symptoms. Parents of high and low scorers were interviewed using semi-structured interviews probing for psychopathology and individuals likely to have RAD were offered face-to-face assessment.

Results: Questionnaire data were available from 92.8% of teachers and 65.8% of parents. Assessments were conducted with 50% of those invited and missing data were imputed--based on the baseline data--for the rest. We calculated that there would be 23 children with definite RAD diagnoses, suggesting that the prevalence of RAD in this population was 1.40% (95% CI 0.94-2.10).

Conclusions: In this deprived general population, RAD was not rare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1192/bjp.bp.112.114074DOI Listing
May 2013

A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni.

PLoS Negl Trop Dis 2012 Jan 10;6(1):e1455. Epub 2012 Jan 10.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0001455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254664PMC
January 2012

Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry.

Nature 2011 Aug 14;477(7363):203-6. Epub 2011 Aug 14.

CNRS UMR 7205, Muséum National d'Histoire Naturelle, CP50, 45 Rue Buffon, 75005 Paris, France.

Supergenes are tight clusters of loci that facilitate the co-segregation of adaptive variation, providing integrated control of complex adaptive phenotypes. Polymorphic supergenes, in which specific combinations of traits are maintained within a single population, were first described for 'pin' and 'thrum' floral types in Primula and Fagopyrum, but classic examples are also found in insect mimicry and snail morphology. Understanding the evolutionary mechanisms that generate these co-adapted gene sets, as well as the mode of limiting the production of unfit recombinant forms, remains a substantial challenge. Here we show that individual wing-pattern morphs in the polymorphic mimetic butterfly Heliconius numata are associated with different genomic rearrangements at the supergene locus P. These rearrangements tighten the genetic linkage between at least two colour-pattern loci that are known to recombine in closely related species, with complete suppression of recombination being observed in experimental crosses across a 400-kilobase interval containing at least 18 genes. In natural populations, notable patterns of linkage disequilibrium (LD) are observed across the entire P region. The resulting divergent haplotype clades and inversion breakpoints are found in complete association with wing-pattern morphs. Our results indicate that allelic combinations at known wing-patterning loci have become locked together in a polymorphic rearrangement at the P locus, forming a supergene that acts as a simple switch between complex adaptive phenotypes found in sympatry. These findings highlight how genomic rearrangements can have a central role in the coexistence of adaptive phenotypes involving several genes acting in concert, by locally limiting recombination and gene flow.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature10341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717454PMC
August 2011

Characterization of a hotspot for mimicry: assembly of a butterfly wing transcriptome to genomic sequence at the HmYb/Sb locus.

Mol Ecol 2010 Mar;19 Suppl 1:240-54

Department of Zoology, University of Cambridge, UK.

The mimetic wing patterns of Heliconius butterflies are an excellent example of both adaptive radiation and convergent evolution. Alleles at the HmYb and HmSb loci control the presence/absence of hindwing bar and hindwing margin phenotypes respectively between divergent races of Heliconius melpomene, and also between sister species. Here, we used fine-scale linkage mapping to identify and sequence a BAC tilepath across the HmYb/Sb loci. We also generated transcriptome sequence data for two wing pattern forms of H. melpomene that differed in HmYb/Sb alleles using 454 sequencing technology. Custom scripts were used to process the sequence traces and generate transcriptome assemblies. Genomic sequence for the HmYb/Sb candidate region was annotated both using the MAKER pipeline and manually using transcriptome sequence reads. In total, 28 genes were identified in the HmYb/Sb candidate region, six of which have alternative splice forms. None of these are orthologues of genes previously identified as being expressed in butterfly wing pattern development, implying previously undescribed molecular mechanisms of pattern determination on Heliconius wings. The use of next-generation sequencing has therefore facilitated DNA annotation of a poorly characterized genome, and generated hypotheses regarding the identity of wing pattern at the HmYb/Sb loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-294X.2009.04475.xDOI Listing
March 2010

Genomic hotspots for adaptation: the population genetics of Müllerian mimicry in the Heliconius melpomene clade.

PLoS Genet 2010 Feb 5;6(2):e1000794. Epub 2010 Feb 5.

Department of Zoology, University of Cambridge, Cambridge, United Kingdom.

Wing patterning in Heliconius butterflies is a longstanding example of both Müllerian mimicry and phenotypic radiation under strong natural selection. The loci controlling such patterns are "hotspots" for adaptive evolution with great allelic diversity across different species in the genus. We characterise nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium, and candidate gene expression at two loci and across multiple hybrid zones in Heliconius melpomene and relatives. Alleles at HmB control the presence or absence of the red forewing band, while alleles at HmYb control the yellow hindwing bar. Across HmYb two regions, separated by approximately 100 kb, show significant genotype-by-phenotype associations that are replicated across independent hybrid zones. In contrast, at HmB a single peak of association indicates the likely position of functional sites at three genes, encoding a kinesin, a G-protein coupled receptor, and an mRNA splicing factor. At both HmYb and HmB there is evidence for enhanced linkage disequilibrium (LD) between associated sites separated by up to 14 kb, suggesting that multiple sites are under selection. However, there was no evidence for reduced variation or deviations from neutrality that might indicate a recent selective sweep, consistent with these alleles being relatively old. Of the three genes showing an association with the HmB locus, the kinesin shows differences in wing disc expression between races that are replicated in the co-mimic, Heliconius erato, providing striking evidence for parallel changes in gene expression between Müllerian co-mimics. Wing patterning loci in Heliconius melpomene therefore show a haplotype structure maintained by selection, but no evidence for a recent selective sweep. The complex genetic pattern contrasts with the simple genetic basis of many adaptive traits studied previously, but may provide a better model for most adaptation in natural populations that has arisen over millions rather than tens of years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1000794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816687PMC
February 2010

An unusual exit point from an electrocution injury.

Burns 2010 Aug 22;36(5):e75-7. Epub 2009 Dec 22.

Department of Plastic and Reconstructive Surgery, St. James's Hospital, Dublin 8, Ireland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.burns.2009.09.007DOI Listing
August 2010