Curating gene variant databases (LSDBs): Toward a universal standard

Celli, Jacopo; Dalgleish, Raymond; Vihinen, Mauno; Taschner, Peter E.M.; Dunnen, Johan T. den

doi:10.1002/humu.21626

Cited by 43 publications

(48 citation statements)

References 25 publications

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“…We also engaged in this task because the scientific community has expressed the importance and the need for establishing a dedicated XLMTM database (mutational and clinical). 23 The implementation and curation of this LSDB followed guidelines reported elsewhere, 32,33 and is registered with the HGVS (LSDB list, http://www.hgvs.org/ dblist/glsdb.html).…”

Section: Mtm1-lovdmentioning

confidence: 99%

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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Myotubular myopathy (MIM#310400), the X-linked form of Centronuclear myopathy (CNM) is mainly characterized by neonatal hypotonia and inability to maintain unassisted respiration. The MTM1 gene, responsible for this disease, encodes myotubularin -a lipidic phosphatase involved in vesicle trafficking regulation and maturation. Recently, it was shown that myotubularin interacts with desmin, being a major regulator of intermediate filaments. We report the development of a locus-specific database for MTM1 using the Leiden Open Variation database software (http://www.lovd.nl/MTM1), with data collated for 474 mutations identified in 472 patients (by June 2012). Among the entries are a total of 25 new mutations, including a large deletion encompassing introns 2-15. During database implementation it was noticed that no large duplications had been reported. We tested a group of eight uncharacterized CNM patients for this specific type of mutation, by multiple ligationdependent probe amplification (MLPA) analysis. A large duplication spanning exons 1-5 was identified in a boy with a mild phenotype, with results pointing toward possible somatic mosaicism. Further characterization revealed that this duplication causes an in-frame deletion at the mRNA level (r.343_444del). Results obtained with a next generation sequencing approach suggested that the duplication extends into the neighboring MAMLD1 gene and subsequent cDNA analysis detected the presence of a MTM1/MAMLD1 fusion transcript. A complex rearrangement involving the duplication of exon 10 has since been reported, with detection also enabled by MLPA analysis. It is thus conceivable that large duplications in MTM1 may account for a number of CNM cases that have remained genetically unresolved.

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Section: Mtm1-lovdmentioning

confidence: 99%

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Oliveira

Kreß

et al. 2012

Eur J Hum Genet

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“…In the current situation, for example, locus-specific variation database (LSDB) curators spend lots of time trying to match information in publications to sequence entries [9]. Numbering schemes may differ depending on the field as well as the utilized reference sequences, further confusing matters.…”

Section: Reference Sequencesmentioning

confidence: 99%

Muddled genetic terms miss and mess the message

Vihinen

2015

Trends in Genetics

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Muddled genetic terms miss and mess the message. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Vihinen, Mauno• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Muddled genetic terms miss and mess the message Mauno VihinenDepartment of Experimental Medical Science, Lund University, BMC D10, SE-22184 Lund, Sweden A critical aspect of science is the clear communication of complicated matters. However, language is often ambiguous, and the message can get lost in the telling. In particular, genetic terms can have different meanings for different people. Here, I discuss this problem and suggest remedies to clarify the message.

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“…For more details about anonymization see Celli et al (2011). The recommendation to limit links to other databases is to protect individuals when data exist in several LSDBs.…”

Section: Ethicsmentioning

confidence: 99%

“…Recommendations have been made, for example, for LSDB content [Claustres et al, 2002;Horaitis and Cotton, 2005;Scriver et al, 1999Scriver et al, , 2000, ethics Povey et al, 2010], data collection [Cotton et al, 2007, somatic variations [Olivier et al, 2009], interpretation and reporting of variants [Plon et al, 2008;Richards et al, 2008], curation [Cotton et al, 2008;Celli et al, 2011] data sharing , and nomenclature, [den Dunnen and Antonarakis, 2000;Taschner and den Dunnen, 2011]. These instructions have been useful, however, some of them are already partly outdated and others are scattered throughout a number of publications.…”

Section: Introductionmentioning

confidence: 99%

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Guidelines for establishing locus specific databases

et al. 2011

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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.

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Curating gene variant databases (LSDBs): Toward a universal standard

Cited by 43 publications

References 25 publications

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Expanding the MTM1 mutational spectrum: novel variants including the first multi-exonic duplication and development of a locus-specific database

Muddled genetic terms miss and mess the message

Guidelines for establishing locus specific databases

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