Publications by authors named "Raymond Dalgleish"

36 Publications

HUGO Gene Nomenclature Committee (HGNC) recommendations for the designation of gene fusions.

Leukemia 2021 Oct 6. Epub 2021 Oct 6.

Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.

Gene fusions have been discussed in the scientific literature since they were first detected in cancer cells in the early 1980s. There is currently no standardized way to denote the genes involved in fusions, but in the majority of publications the gene symbols in question are listed either separated by a hyphen (-) or by a forward slash (/). Both types of designation suffer from important shortcomings. HGNC has worked with the scientific community to determine a new, instantly recognizable and unique separator-a double colon (::)-to be used in the description of fusion genes, and advocates its usage in all databases and articles describing gene fusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41375-021-01436-6DOI Listing
October 2021

A common classification framework for histone sequence alterations in tumours: an expert consensus proposal.

J Pathol 2021 Jun 7;254(2):109-120. Epub 2021 May 7.

International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.

The description of genetic alterations in tumours is of increasing importance. In human genetics, and in pathology reports, sequence alterations are given using the human genome variation society (HGVS) guidelines for the description of such variants. However, there is less adherence to these guidelines for sequence variations in histone genes. Due to early cleavage of the N-terminal methionine in most histones, the description of histone sequence alterations follows their own nomenclature and differs from the HGVS-compliant numbering by omitting this first amino acid. Next generation sequencing reports, however, follow the HGVS guidelines and as a result, an unambiguous description of sequence variants in histones cannot be provided. The coexistence of these two nomenclatures leads to confusions for pathologists, oncologists, and researchers. This review provides an overview of tumour entities with sequence alterations of the H3-3A gene (HGNC ID = HGNC:4764), highlights the problems associated with the coexistence of these two nomenclatures, and proposes a standard for the reporting of histone sequence variants that allows an unambiguous description of these variants according to HGVS principles. We hope that scientific journals will adopt the new notation, and that both geneticists and pathologists will include it in their reports. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/path.5666DOI Listing
June 2021

Verifying nomenclature of DNA variants in submitted manuscripts: Guidance for journals.

Hum Mutat 2021 Jan 10;42(1):3-7. Epub 2020 Dec 10.

Department of Genetic Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Documenting variation in our genomes is important for research and clinical care. Accuracy in the description of DNA variants is therefore essential. To address this issue, the Human Variome Project convened a committee to evaluate the feasibility of requiring authors to verify that all variants submitted for publication complied with a widely accepted standard for description. After a pilot study of two journals, the committee agreed that requiring authors to verify that variants complied with Human Genome Variation Society nomenclature is a reasonable step toward standardizing the worldwide inventory of human variation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.24144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961887PMC
January 2021

EMQN best practice guidelines for genetic testing in dystrophinopathies.

Eur J Hum Genet 2020 09 18;28(9):1141-1159. Epub 2020 May 18.

Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

Dystrophinopathies are X-linked diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy, due to DMD gene variants. In recent years, the application of new genetic technologies and the availability of new personalised drugs have influenced diagnostic genetic testing for dystrophinopathies. Therefore, these European best practice guidelines for genetic testing in dystrophinopathies have been produced to update previous guidelines published in 2010.These guidelines summarise current recommended technologies and methodologies for analysis of the DMD gene, including testing for deletions and duplications of one or more exons, small variant detection and RNA analysis. Genetic testing strategies for diagnosis, carrier testing and prenatal diagnosis (including non-invasive prenatal diagnosis) are then outlined. Guidelines for sequence variant annotation and interpretation are provided, followed by recommendations for reporting results of all categories of testing. Finally, atypical findings (such as non-contiguous deletions and dual DMD variants), implications for personalised medicine and clinical trials and incidental findings (identification of DMD gene variants in patients where a clinical diagnosis of dystrophinopathy has not been considered or suspected) are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41431-020-0643-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608854PMC
September 2020

hgvs: A Python package for manipulating sequence variants using HGVS nomenclature: 2018 Update.

Hum Mutat 2018 12 5;39(12):1803-1813. Epub 2018 Sep 5.

Invitae, Inc., San Francisco, California.

The Human Genome Variation Society (HGVS) nomenclature guidelines encourage the accurate and standard description of DNA, RNA, and protein sequence variants in public variant databases and the scientific literature. Inconsistent application of the HGVS guidelines can lead to misinterpretation of variants in clinical settings. Reliable software tools are essential to ensure consistent application of the HGVS guidelines when reporting and interpreting variants. We present the hgvs Python package, a comprehensive tool for manipulating sequence variants according to the HGVS nomenclature guidelines. Distinguishing features of the hgvs package include: (1) parsing, formatting, validating, and normalizing variants on genome, transcript, and protein sequences; (2) projecting variants between aligned sequences, including those with gapped alignments; (3) flexible installation using remote or local data (fully local installations eliminate network dependencies); (4) extensive automated tests; and (5) open source development by a community from eight organizations worldwide. This report summarizes recent and significant updates to the hgvs package since its original release in 2014, and presents results of extensive validation using clinical relevant variants from ClinVar and HGMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282708PMC
December 2018

Mutations in COL1A1 Gene Change Dentin Nanostructure: A Response.

Anat Rec (Hoboken) 2018 08 26;301(8):1307-1308. Epub 2018 Apr 26.

Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ar.23814DOI Listing
August 2018

VariantValidator: Accurate validation, mapping, and formatting of sequence variation descriptions.

Hum Mutat 2018 01 17;39(1):61-68. Epub 2017 Oct 17.

Department of Genetics, University of Leicester, Leicester, United Kingdom.

The Human Genome Variation Society (HGVS) variant nomenclature is widely used to describe sequence variants in scientific publications, clinical reports, and databases. However, the HGVS recommendations are complex and this often results in inaccurate variant descriptions being reported. The open-source hgvs Python package (https://github.com/biocommons/hgvs) provides a programmatic interface for parsing, manipulating, formatting, and validating of variants according to the HGVS recommendations, but does not provide a user-friendly Web interface. We have developed a Web-based variant validation tool, VariantValidator (https://variantvalidator.org/), which utilizes the hgvs Python package and provides additional functionality to assist users who wish to accurately describe and report sequence-level variations that are compliant with the HGVS recommendations. VariantValidator was designed to ensure that users are guided through the intricacies of the HGVS nomenclature, for example, if the user makes a mistake, VariantValidator automatically corrects the mistake if it can, or provides helpful guidance if it cannot. In addition, VariantValidator has the facility to interconvert genomic variant descriptions in HGVS and Variant Call Format with a degree of accuracy that surpasses most competing solutions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765404PMC
January 2018

The collαgen III fibril has a "flexi-rod" structure of flexible sequences interspersed with rigid bioactive domains including two with hemostatic roles.

PLoS One 2017 13;12(7):e0175582. Epub 2017 Jul 13.

From the University of Melbourne Department of Medicine (Northern Health), Melbourne, VIC, Australia.

Collagen III is critical to the integrity of blood vessels and distensible organs, and in hemostasis. Examination of the human collagen III interactome reveals a nearly identical structural arrangement and charge distribution pattern as for collagen I, with cell interaction domains, fibrillogenesis and enzyme cleavage domains, several major ligand-binding regions, and intermolecular crosslink sites at the same sites. These similarities allow heterotypic fibril formation with, and substitution by, collagen I in embryonic development and wound healing. The collagen III fibril assumes a "flexi-rod" structure with flexible zones interspersed with rod-like domains, which is consistent with the molecule's prominence in young, pliable tissues and distensible organs. Collagen III has two major hemostasis domains, with binding motifs for von Willebrand factor, α2β1 integrin, platelet binding octapeptide and glycoprotein VI, consistent with the bleeding tendency observed with COL3A1 disease-causing sequence variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175582PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509119PMC
September 2017

HGVS Recommendations for the Description of Sequence Variants: 2016 Update.

Hum Mutat 2016 06 25;37(6):564-9. Epub 2016 Mar 25.

Generade Centre of Expertise Genomics and University of Applied Sciences Leiden, Leiden, The Netherlands.

The consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome. In particular, DNA diagnostics critically depends on accurate and standardized description and sharing of the variants detected. The sequence variant nomenclature system proposed in 2000 by the Human Genome Variation Society has been widely adopted and has developed into an internationally accepted standard. The recommendations are currently commissioned through a Sequence Variant Description Working Group (SVD-WG) operating under the auspices of three international organizations: the Human Genome Variation Society (HGVS), the Human Variome Project (HVP), and the Human Genome Organization (HUGO). Requests for modifications and extensions go through the SVD-WG following a standard procedure including a community consultation step. Version numbers are assigned to the nomenclature system to allow users to specify the version used in their variant descriptions. Here, we present the current recommendations, HGVS version 15.11, and briefly summarize the changes that were made since the 2000 publication. Most focus has been on removing inconsistencies and tightening definitions allowing automatic data processing. An extensive version of the recommendations is available online, at http://www.HGVS.org/varnomen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22981DOI Listing
June 2016

LSDBs and How They Have Evolved.

Hum Mutat 2016 06 14;37(6):532-9. Epub 2016 Mar 14.

Department of Genetics, University of Leicester, Leicester, United Kingdom.

Locus specific databases (LSDBs) make a key contribution to our understanding of heritable and acquired human disorders, disease susceptibility, and adverse drug reactions. As data have accumulated in LSDBs, a greater reliance on their use has arisen in clinical practice. Even though LSDBs have existed in recognizable form for only a quarter of a century, their origin lies in the manual cataloging of data that began around 50 years ago. Analysis and recording of sequence variation in the globin genes, and the proteins which they encode, can confidently be said to be the foundation for what we now refer to as LSDBs. Their growth over the years has primarily been underpinned by software developments and the advent of the World Wide Web. However, it is also important to recognize the evolution of reporting standards and reference sequences, without which accurate and consistent reporting of sequence variants would be impossible. Nowadays, LSDBs exist for many human protein-coding genes and the focus of efforts has moved toward minor tidying up of the variant reporting nomenclature and processes for assuring the completeness, correctness, and consistency of the data. The next 25 years will doubtless witness further developments in the evolution of LSDBs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22979DOI Listing
June 2016

Cafe Variome: general-purpose software for making genotype-phenotype data discoverable in restricted or open access contexts.

Hum Mutat 2015 Oct 25;36(10):957-64. Epub 2015 Aug 25.

Department of Genetics, University of Leicester, Leicester, UK.

Biomedical data sharing is desirable, but problematic. Data "discovery" approaches-which establish the existence rather than the substance of data-precisely connect data owners with data seekers, and thereby promote data sharing. Cafe Variome (http://www.cafevariome.org) was therefore designed to provide a general-purpose, Web-based, data discovery tool that can be quickly installed by any genotype-phenotype data owner, or network of data owners, to make safe or sensitive content appropriately discoverable. Data fields or content of any type can be accommodated, from simple ID and label fields through to extensive genotype and phenotype details based on ontologies. The system provides a "shop window" in front of data, with main interfaces being a simple search box and a powerful "query-builder" that enable very elaborate queries to be formulated. After a successful search, counts of records are reported grouped by "openAccess" (data may be directly accessed), "linkedAccess" (a source link is provided), and "restrictedAccess" (facilitated data requests and subsequent provision of approved records). An administrator interface provides a wide range of options for system configuration, enabling highly customized single-site or federated networks to be established. Current uses include rare disease data discovery, patient matchmaking, and a Beacon Web service.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22841DOI Listing
October 2015

Transcription factor SOHLH1 potentially associated with primary ovarian insufficiency.

Fertil Steril 2015 Feb 17;103(2):548-53.e5. Epub 2014 Dec 17.

Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China. Electronic address:

Objective: To investigate whether gene variants of SOHLH1 exist in Chinese and Serbian patients with primary ovarian insufficiency (POI).

Design: Case-control genetic study.

Setting: University hospitals.

Patient(s): A total of 364 Han Chinese and 197 Serbian women with nonsyndromic POI and ethnically matched controls.

Intervention(s): None.

Main Outcome Measure(s): SOHLH1 gene sequencing.

Result(s): We found 10 novel heterozygous variants in our cohorts of 561 women with POI but none in the 600 ethnically matched controls. Statistical and bioinformatic analyses indicated that three of the eight variants in Chinese POI cases are potentially disease causing. They comprise two missense variants (p.Ser317Phe and p.Glu376Lys) that might each change activity of the SOHLH1 protein as a transcription factor and one variant (c.*118C>T) located in the 3' untranslated region of the SOHLH1 gene, which might generate a new binding site for the microRNA hsa-miR-888-5p. Of the two variants in the Serbian POI cases, both were synonymous, and no missense variant was identified. The allele frequencies of some known single-nucleotide polymorphisms were statistically significantly different between patients and controls in both the Chinese and Serbian groups.

Conclusion(s): Our results suggest that SOHLH1 may be regarded as a new candidate gene for POI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2014.11.011DOI Listing
February 2015

The Human Variome Project: ensuring the quality of DNA variant databases in inherited renal disease.

Pediatr Nephrol 2015 Nov 11;30(11):1893-901. Epub 2014 Nov 11.

Research Department of Genetics, Evolution and Environment, University College London, London, UK.

A recent review identified 60 common inherited renal diseases caused by DNA variants in 132 different genes. These diseases can be diagnosed with DNA sequencing, but each gene probably also has a thousand normal variants. Many more normal variants have been characterised by individual laboratories than are reported in the literature or found in publicly accessible collections. At present, testing laboratories must assess each novel change they identify for pathogenicity, even when this has been done elsewhere previously, and the distinction between normal and disease-associated variants is particularly an issue with the recent surge in exomic sequencing and gene discovery projects. The Human Variome Project recommends the establishment of gene-specific DNA variant databases to facilitate the sharing of DNA variants and decisions about likely disease causation. Databases improve diagnostic accuracy and testing efficiency, and reduce costs. They also help with genotype-phenotype correlations and predictive algorithms. The Human Variome Project advocates databases that use standardised descriptions, are up-to-date, include clinical information and are freely available. Currently, the genes affected in the most common inherited renal diseases correspond to 350 different variant databases, many of which are incomplete or have insufficient clinical details for genotype-phenotype correlations. Assistance is needed from nephrologists to maximise the usefulness of these databases for the diagnosis and management of inherited renal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-014-2994-1DOI Listing
November 2015

Novel variants in the SOHLH2 gene are implicated in human premature ovarian failure.

Fertil Steril 2014 Apr 10;101(4):1104-1109.e6. Epub 2014 Feb 10.

Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China; Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. Electronic address:

Objective: To determine whether variants in the SOHLH2 gene contribute to human premature ovarian failure (POF) in different ethnicities.

Design: Case-control genetic study.

Setting: University hospitals.

Patient(s): Chinese (364 cases) and Serbian (197 cases) women with nonsyndromic POF and ethnically matched controls.

Intervention(s): None.

Main Outcome Measure(s): Variation analysis of the SOHLH2 gene.

Result(s): Eleven novel heterozygous variants were identified in cohorts of POF but were absent in matched controls. These included the nonsynonymous variants p.Glu79Lys (n = 2 cases), p.Glu105Gly, and p.Thr321Pro, which were found among four Chinese POF cases, and p.Leu120Phe (n = 3 cases) and p.Leu204Phe, which were found among four Serbian women. Protein alignments reveal that p.Glu79Lys and p.Glu105Gly involve amino acids highly conserved among mammals, both of which are predicted to be deleterious. The c.-210G>T found in the Chinese POF cohort lies in the core promoter region, which is enriched with transcription factor binding sites and CpG islands. In the Serbian cohort, the variant most likely to have a deleterious effect is c.530+6T>G, which is predicted to affect RNA splicing and result in nonsense mediated decay of transcripts. The other variants are less likely to be deleterious. Disturbing the expression, transactivation or homo-/ heterodimerization of the SOHLH2 protein could result in ovarian failure. Overall, four of the 11 novel variants seem plausible explanations for POF; the other seven variants are less likely but cannot be categorically excluded.

Conclusion(s): Our identification of novel variants in the SOHLH2 gene, in women with POF of both Chinese and Serbian origin, strongly suggests an important role for SOHLH2 in human POF etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2014.01.001DOI Listing
April 2014

Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants.

Nucleic Acids Res 2014 Jan 26;42(Database issue):D873-8. Epub 2013 Nov 26.

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK, National Center for Biotechnology Information, Bethesda, MD 20894, USA, and Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.

Locus Reference Genomic (LRG; http://www.lrg-sequence.org/) records contain internationally recognized stable reference sequences designed specifically for reporting clinically relevant sequence variants. Each LRG is contained within a single file consisting of a stable 'fixed' section and a regularly updated 'updatable' section. The fixed section contains stable genomic DNA sequence for a genomic region, essential transcripts and proteins for variant reporting and an exon numbering system. The updatable section contains mapping information, annotation of all transcripts and overlapping genes in the region and legacy exon and amino acid numbering systems. LRGs provide a stable framework that is vital for reporting variants, according to Human Genome Variation Society (HGVS) conventions, in genomic DNA, transcript or protein coordinates. To enable translation of information between LRG and genomic coordinates, LRGs include mapping to the human genome assembly. LRGs are compiled and maintained by the National Center for Biotechnology Information (NCBI) and European Bioinformatics Institute (EBI). LRG reference sequences are selected in collaboration with the diagnostic and research communities, locus-specific database curators and mutation consortia. Currently >700 LRGs have been created, of which >400 are publicly available. The aim is to create an LRG for every locus with clinical implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkt1198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965024PMC
January 2014

Variobox: automatic detection and annotation of human genetic variants.

Hum Mutat 2014 Feb 21;35(2):202-7. Epub 2013 Nov 21.

DETI/IEETA, University of Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.

Triggered by the sequencing of the human genome, personalized medicine has been one of the fastest growing research areas in the last decade. Multiple software and hardware technologies have been developed by several projects, culminating in the exponential growth of genetic data. Considering the technological developments in this field, it is now fairly easy and inexpensive to obtain genetic profiles for unique individuals, such as those performed by several genetic analysis companies. The availability of computational tools that simplify genetic data analysis and the disclosure of biomedical evidences are of utmost importance. We present Variobox, a desktop tool to annotate, analyze, and compare human genes. Variobox obtains variant annotation data from WAVe, protein metadata annotations from Protein Data Bank, and sequences are obtained from Locus Reference Genomic or RefSeq databases. To explore the data, Variobox provides an advanced sequence visualization that enables agile navigation through genetic regions. DNA sequencing data can be compared with reference sequences retrieved from LRG or RefSeq records, identifying and automatically annotating new potential variants. These features and data, ranging from patient sequences to HGVS-compliant variant descriptions, are combined in an intuitive interface to analyze genes and variants. Variobox is a Java application, available at http://bioinformatics.ua.pt/variobox.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22474DOI Listing
February 2014

Ethnic specificity of variants of the ESR1, HK3, BRSK1 genes and the 8q22.3 locus: no association with premature ovarian failure (POF) in Serbian women.

Maturitas 2014 Jan 20;77(1):64-7. Epub 2013 Sep 20.

Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China; Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objective: To identify whether variants found in a large Han Chinese cohort - 8q22.3 SNPs rs3847153 and rs3108910; and one SNP each in HK3 (rs2278493), ESR1 (rs2234693) and BRSK1 (rs12611091) - are associated with premature ovarian failure (POF) in a different ethnic group (Serbian).

Design: Case-control genetic association study in 197 Serbian POF cases and 552 matched controls.

Results: None of the SNPs found associated with POF in Chinese cohort were found to be associated in the Serbian sample.

Conclusions: In contrast to Han Chinese, no association was found between POF in Serbian women and any of the four tested loci: 8q22.3, HK3, ESR1 and BRSK1. This indicates that ethnically distinct populations may show differences in gene-regulating pathways and genes causing POF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2013.09.006DOI Listing
January 2014

Quantifying the use of bioresources for promoting their sharing in scientific research.

Gigascience 2013 May 1;2(1). Epub 2013 May 1.

Epidémiologie et analyses en santé publique, Faculté de médecine, UMR1027 INSERM-Université de Toulouse III, 37 allées Jules Guesde, Toulouse Cedex 7, F-31073, France.

An increasing portion of biomedical research relies on the use of biobanks and databases. Sharing of such resources is essential for optimizing knowledge production. A major obstacle for sharing bioresources is the lack of recognition for the efforts involved in establishing, maintaining and sharing them, due to, in particular, the absence of adequate tools. Increasing demands on biobanks and databases to improve access should be complemented with efforts of end-users to recognize and acknowledge these resources. An appropriate set of tools must be developed and implemented to measure this impact.To address this issue we propose to measure the use in research of such bioresources as a value of their impact, leading to create an indicator: Bioresource Research Impact Factor (BRIF). Key elements to be assessed are: defining obstacles to sharing samples and data, choosing adequate identifier for bioresources, identifying and weighing parameters to be considered in the metrics, analyzing the role of journal guidelines and policies for resource citing and referencing, assessing policies for resource access and sharing and their influence on bioresource use. This work allows us to propose a framework and foundations for the operational development of BRIF that still requires input from stakeholders within the biomedical community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2047-217X-2-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655103PMC
May 2013

VarioML framework for comprehensive variation data representation and exchange.

BMC Bioinformatics 2012 Oct 3;13:254. Epub 2012 Oct 3.

Institute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.

Background: Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement.

Results: The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components.

Conclusions: VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2105-13-254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507772PMC
October 2012

Clinical utility gene card for: osteogenesis imperfecta.

Eur J Hum Genet 2013 Jun 26;21(6). Epub 2012 Sep 26.

Department of Clinical Genetics, Center for Connective Tissue Disorders, VU University Medical Center, Amsterdam, The Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2012.210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3658202PMC
June 2013

Solving bottlenecks in data sharing in the life sciences.

Hum Mutat 2012 Oct 18;33(10):1494-6. Epub 2012 Jun 18.

Department of Genetics, University of Leicester, Leicester, United Kingdom.

The joint Open PHACTS/GEN2PHEN workshop on "Solving Bottlenecks in Data Sharing in the Life Sciences" was held in Volendam, the Netherlands, on September 19 and 20, 2011, and was attended by representatives from academia, industry, publishing, and funding agencies. The aim of the workshop was to explore the issues that influence the extent to which data in the life sciences are shared, and to explore sustainability scenarios that would enable and promote "open" data sharing. Several key challenges were identified and solutions to each of these were proposed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22123DOI Listing
October 2012

Guidelines for establishing locus specific databases.

Hum Mutat 2012 Feb 9;33(2):298-305. Epub 2011 Dec 9.

Institute of Biomedical Technology, University of Tampere, Finland.

Information about genetic variation has been collected for some 20 years into registries, known as locus specific databases (LSDBs), which nowadays often contain information in addition to the actual genetic variation. Several issues have to be taken into account when considering establishing and maintaining LSDBs and these have been discussed previously in a number of articles describing guidelines and recommendations. This information is widely scattered and, for a newcomer, it would be difficult to obtain the latest information and guidance. Here, a sequence of steps essential for establishing an LSDB is discussed together with guidelines for each step. Curators need to collect information from various sources, code it in systematic way, and distribute to the research and clinical communities. In doing this, ethical issues have to be taken into account. To facilitate integration of information to, for example, analyze genotype-phenotype correlations, systematic data representation using established nomenclatures, data models, and ontologies is essential. LSDB curation and maintenance comprises a number of tasks that can be managed by following logical steps. These resources are becoming ever more important and new curators are essential to ensure that we will have expertly curated databases for all disease-related genes in the near future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.21646DOI Listing
February 2012

Curating gene variant databases (LSDBs): toward a universal standard.

Hum Mutat 2012 Feb 3;33(2):291-7. Epub 2011 Nov 3.

Human and Clinical Genetics, Leiden University Medical Center, Leiden, Netherlands.

Gene variant databases or Locus-Specific DataBases (LSDBs) are used to collect and display information on sequence variants on a gene-by-gene basis. Their most frequent use is in relation to DNA-based diagnostics, giving clinicians and scientists easy access to an up-to-date overview of all gene variants identified worldwide and whether they influence the function of the gene ("pathogenic or not"). While literature on gene variant databases is extensive, little has been published on the process of database curation itself. Based on our extensive experience as LSDB curators and our contributions to database curation courses, we discuss the subject of database curation. We describe the tasks involved, the steps to take, and the issues that might occur. Our overview is a first step toward establishing overall guidelines for database curation and ultimately covers one aspect of establishing quality-assured gene variant databases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.21626DOI Listing
February 2012

EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta.

Eur J Hum Genet 2012 Jan 10;20(1):11-9. Epub 2011 Aug 10.

Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands.

Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to 'exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ejhg.2011.141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234509PMC
January 2012

WAVe: web analysis of the variome.

Hum Mutat 2011 Jul 7;32(7):729-34. Epub 2011 Apr 7.

DETI/IEETA, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.

DNA sequence variation is the underlying basis of common human traits and rarer single-gene disorders. Understanding the variome, the variants in an individual's genome, is essential to enable the ultimate goals of personalized medicine. This critical research field has grown dramatically in recent years, mostly due to the spread and development of genotyping technologies. Despite these activities being promoted by the Human Genome Variation Society and projects such as the Human Variome Project or the European GEN2PHEN Project, variome data-integration systems are far from being widely used in the research community workflow. Most of ongoing research is focused on improving locus-specific databases. Although the quality and manual curation of LSDBs adds true value to this domain, they are often narrow, heterogeneous, and independent systems. This hampers data harmonization and interoperability between systems, stifling the aggregation of data from LSDBs and related data sources. A new platform entitled Web Analysis of the Variome, WAVe, is introduced. It offers direct and programmatic access to multiple locus-specific databases, with the integration of genetic variation datasets and enrichment with relevant information. WAVe's agile and innovative Web interface is accessible at http://bioinformatics.ua.pt/WAVe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.21499DOI Listing
July 2011

Bilateral consecutive rupture of the quadriceps tendon in a man with BstUI polymorphism of the COL5A1 gene.

Knee Surg Sports Traumatol Arthrosc 2011 Aug 17;19(8):1403; author reply 1404-5. Epub 2011 Feb 17.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00167-011-1408-1DOI Listing
August 2011

Practical guidelines addressing ethical issues pertaining to the curation of human locus-specific variation databases (LSDBs).

Hum Mutat 2010 Nov;31(11):1179-84

Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.

More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.21339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2992689PMC
November 2010

Locus Reference Genomic sequences: an improved basis for describing human DNA variants.

Genome Med 2010 Apr 15;2(4):24. Epub 2010 Apr 15.

Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.

As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specific purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-file record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)-approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants affecting human health. Further information can be found on the LRG web site: http://www.lrg-sequence.org.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/gm145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873802PMC
April 2010

The Human Variome Project (HVP) 2009 Forum "Towards Establishing Standards".

Hum Mutat 2010 Mar;31(3):366-7

Genomic Disorders Research Centre, Carlton South, Victoria, Australia.

The May 2009 Human Variome Project (HVP) Forum "Towards Establishing Standards" was a round table discussion attended by delegates from groups representing international efforts aimed at standardizing several aspects of the HVP: mutation nomenclature, description and annotation, clinical ontology, means to better characterize unclassified variants (UVs), and methods to capture mutations from diagnostic laboratories for broader distribution to the medical genetics research community. Methods for researchers to receive credit for their effort at mutation detection were also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.21175DOI Listing
March 2010
-->