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Human Genome Organization

Nomenclature Standards

HGNC (HUGO Gene Nomenclature Committee)

The HGNC is responsible for approving unique symbols and names for human loci, including protein coding genes, ncRNA genes and pseudogenes, to allow unambiguous scientific communication.

For each known human gene we approve a gene name and symbol (short-form abbreviation), as well as a unique HGNC identifier (ID), which are stored in the HGNC database, www.genenames.org. This is a curated online repository of HGNC-approved gene nomenclature, gene groups and associated resources including links to genomic, proteomic and phenotypic information. Ideally, gene symbols are short, memorable and pronounceable, and most gene names are long-form descriptions of the symbol. Names should be brief and specific, and should convey something about the character or function of the gene products but not attempt to describe everything known. Each gene is assigned only one symbol; the HGNC does not routinely name isoforms (that is, alternate transcripts or splice variants). Ideally each symbol maintains parallel construction in different members of a gene family and can also be used in other species, especially across vertebrates. Our gene naming guidelines are discussed in Bruford et al., 2020.

Our sister project, the Vertebrate Gene Nomenclature Committee (VGNC, vertebrates.genenames.org), is responsible for assigning standardized names to genes in selected vertebrate species that currently lack a nomenclature committee. The VGNC aims to harmonize vertebrate gene nomenclature in line with human gene nomenclature, with orthologs being assigned the same nomenclature where possible, and also coordinates with the 5 existing vertebrate nomenclature committees for mouse, rat, chicken, Xenopus and zebrafish.

History
Problems of nomenclature in human genetics were recognised as early as the 1960s and in 1979 full guidelines for human gene nomenclature were presented at the Edinburgh Human Genome Meeting (HGM). Since then we have continued to strike a compromise between the convenience and simplicity required for the everyday use of human gene nomenclature and the need for adequate definition of the concepts involved. In 1989, the Nomenclature Committee was placed under the auspices of the newly founded Human Genome Organization (HUGO) and thus became the HUGO Gene Nomenclature Committee (HGNC)

The committee has grown from a single force (Dr Phyllis J. McAlpine) to a team of post-docs and bioinformaticians. For eleven years, from 1996-2007, the HGNC was chaired by Professor Sue Povey and based at University College London. In September 2007 the HGNC relocated to the European Bioinformatics Institute (EBI), and in 2018 became a joint project between the EBI and the University of Cambridge. We are a non-profit making body which is jointly funded by the US National Human Genome Research Institute (NHGRI) and the Wellcome Trust (UK).

HGVS Variant Nomenclature Committee (HVNC)

The HGVS nomenclature standard is authorised by the Human Genome Organisation (HUGO). Activities regarding the nomenclature go through the HGVS Variant Nomenclature Committee (HVNC), a working group of the “HUGO Nomenclature Standards Committee”, with administrative support of the HUGO office. HUGO became the guardian of the HGVS nomenclature standard when in 2021, three organisations; HUGO, HGVS (Human Genome Variation Society) and HVP (Human Variome Project) decided to merge into one organisation.

Discussions regarding the uniform and unequivocal description of sequence variants in DNA and protein sequences (mutations, polymorphisms) were initiated by two papers published in 1993 (Beaudet AL & Tsui LC and Beutler E). The ideas presented were widely discussed, modified, extended and ultimately resulted in the HGVS nomenclature standard, the recommendations for the description of sequence variants, based on a paper published in 2000 (den Dunnen, JT and Antonarakis, SE. 2000, Hum.Mutat. 15:7). Initially the recommendations did not cover all types of variants and a nomenclature website was established to report the latest updates and additions. The last publication covering the recommendations was published in 2016 (den Dunnen, JT et al. 2016, Hum.Mutat. 37:564).

The HGVS nomenclature website contains the latest version of the nomenclature standard. The website gives an overview of all recommendations, the changes made and the extensions approved. In addition, the website provides background information, the definitions used, examples of descriptions based on the nomenclature and links to support tools and educational material. The nomenclature pages can be used as a guide to describe any sequence variant identified. The HVNC takes care of the nomenclature website, answers questions, handles requests to change or extend the recommendations, prepares proposals for community consultation, publishes new versions of the standards and assigns HGVS nomenclature version numbers.

 

The HVNC members:

Johan den Dunnen (Chair)

Peter Causey-Freeman

Peter Taschner

Anne-Francoise Roux

Terence Murphy

Ros Hastings

Reece Hart

Raymond Dalgleish

Oleg Agafonov

 

For more information, please click here 

ISCN (Standing Committee on the International System for Human Cytogenomic Nomenclature)

The need to establish a common system of nomenclature that would improve communication between workers in the field of cytogenetics was first proposed in 1960, four years after the human chromosome number was established. The ‘Proposed Standards System of Nomenclature of Meiotic Chromosomes’ was agreed by consensus amongst investigators in the field at the Denver Conference (1960) and published in the Lancet. Supplements to the nomenclature were published after the London (1963), Chicago (1966) and in Paris (1971) conferences. In 1974 when it became clear that the number of individuals working in the field was too great to allow the majority of laboratories to be represented, so an International Standing Committee on Human Cytogenetic Nomenclature was elected. The Standing Committee elections ensured that an international and geographic representation of the laboratories was achieved. The ‘International System for Human Cytogenetic Nomenclature’ (ISCN) was published in 1978 which included all the major decisions of the four conferences and edited for consistency and accuracy. As techniques were devised to increase the resolutions and new technologies developed, further revisions of the nomenclature were needed resulting in the publication of ISCN (1981), ISCN (1985). Chromosome aberrations associated with Neoplasia were not adequately described by the nomenclature in ISCN (1985) and a supplement ISCN (1991): Guidelines for Cancer Cytogenetics was published.

There have been six subsequent editions in 1995, 2005, 2009, 2013, 2016 and 2020 published. Each introduced further refinements and new nomenclature for different technologies such as QF-PCR, MLPA, real-time-PCR, microarrays etc. In 2014, following at joint session with members of the Human Genome Variation Society (HGVS) Sequence Variant Description Working Group a new sequencing nomenclature was developed that would work for both the molecular genetics and cytogenetics communities. ISCN (2016) included a section on describing chromosome abnormalities characterised by sequencing and the ‘C’ in ISCN was changed to Cytogenomics. Further sequence and microarray examples were included in the ISCN (2020) and due to the increased use of these technologies which orientate chromosomes by nucleotide number from pter to qter, the Standing Committee decided to standardize this approach across all technologies, including banded chromosomes. In addition, it was agree to standardise the presentation of the sex chromosome abnormalities before those affecting autosomes for all technologies.

ISCN has been published as a book and in a peer-reviewed journal since 1960. A web-based version of ISCN (2020) has now been introduced where any amendments to the nomenclature are highlighted and there is a forum for geneticists to ask ISCN related questions or suggest improvements to the nomenclature.

The Standing Committee is currently composed of representatives from the Americas, Europe, Asia and Oceania. A representative of the HGVS committee is also on the Standing Committee. The Chair of the Standing Committee is Dr Ros Hastings (UK) and the Vice-Chair is Sarah Moore (Australia). The Committee currently has a ‘virtually’ every six months and communicates via email or the forum as required.

To summarise, the primary purpose of ISCN is to foster communication amongst cytogeneticists using a standard nomenclature that can be used to describe any genomic rearrangement identified either by standard karyotyping or molecular methodologies.

The ISCN Standards committee works with HGVS and has recently also worked with the HUGO Gene Nomenclature Committee (HGNC). The ISCN Standing Committee welcomes an inclusion of a representative on the HUGO Nomenclature Standards Committee.

Ros Hastings Chair of ISCN Standing Committee