Nomenclature doi:10.1006/geno.2002.6748, available online at http://www.idealibrary.com on IDEAL Guidelines for Human Gene Nomenclature Hester M. Wain, Elspeth A. Bruford, Ruth C. Lovering, Michael J. Lush, Mathew W. Wright, and Sue Povey HUGO Gene Nomenclature Committee, The Galton Laboratory, Department of Biology, University College London, Wolfson House, 4, Stephenson Way, London, NW1 2HE, UK. E-mail: [email protected]. INTRODUCTION 1.2 Locus The word “locus” is not a synonym for gene but refers to a Guidelines for human gene nomenclature were first pub- map position. A more precise definition is given in the Rules lished in 1979 [1], when the Human Gene Nomenclature and Guidelines from the International Committee on Standardized Committee was first given the authority to approve and Genetic Nomenclature for Mice, which states: “A locus is a point implement human gene names and symbols. Updates of these in the genome, identified by a marker, which can be mapped guidelines were published in 1987 [2], 1995 [3], and 1997 [4]. by some means. It does not necessarily correspond to a gene; With the recent publications of the complete human genome it could, for example, be an anonymous non-coding DNA sequence there is an estimated total of 26,000–40,000 genes, segment or a cytogenetic feature. A single gene may have as suggested by the International Human Genome several loci within it (each defined by different markers) and Sequencing Consortium [5] and Venter et al. [6]. Thus, the these markers may be separated in genetic or physical map- guidelines (http://www.gene.ucl.ac.uk/nomenclature/ ping experiments. In such cases, it is useful to define these dif- guidelines.html) have been updated to accommodate their ferent loci, but normally the gene name should be used to application to this wealth of information, although gene sym- designate the gene itself, as this usually will convey the most bols are still only assigned when required for communica- information” (http://www.informatics.jax.org/mgihome/ tion. These updates were derived with input from the HUGO nomen/gene.shtml#trdef). Gene Nomenclature Committee (HGNC) International Advisory Committee and attendees of the ASHG01NW Gene 1.3 Chromosome Region Nomenclature Workshop. All approved human gene sym- In the context of gene nomenclature, “chromosome region” bols can be found in the Genew database [7]. is defined as a genomic region that has been associated with The philosophy of the HGNC remains “that gene nomen- a particular syndrome or phenotype, particularly when there clature should evolve with new technology rather than be is a possibility that several genes within it may be involved restrictive as sometimes occurs when historical and single in the phenotype. Designation of such regions may be gene nomenclature systems are applied” [2]. requested by the scientific community and approved by A summary of the guidelines is presented here: HGNC, e.g., ANCR “Angelman syndrome chromosome 1. Each approved gene symbol must be unique. region” and CECR “cat eye syndrome chromosome region.” 2. Symbols are short-form representations (or abbrevi- Symbols may therefore be assigned to the following: ations) of the descriptive gene name. a) Clearly defined phenotypes shown to be inherited 3. Symbols should only contain Latin letters and Arabic predominantly as monogenic mendelian traits, e.g., numerals. BBS1 “Bardet-Biedl syndrome 1.” 4. Symbols should not contain punctuation. b) Unidentified genes contributing to a complex trait 5. Symbols should not end in “G” for gene. shown by linkage or association with a known 6. Symbols do not contain any reference to species, for marker, e.g., IDDM6 “insulin-dependent diabetes example, “H/h” for human. mellitus 6.” c) Cloned segments of DNA with sufficient structural, functional, and expression data to identify them as 1. CRITERIA FOR SYMBOL ASSIGNMENT transcribed entities, e.g., COX8 “cytochrome c oxi- dase subunit VIII.” 1.1 Gene d) Nonfunctional copies of genes (pseudogenes), e.g., A gene is defined as: “a DNA segment that contributes to IL9RP1 “interleukin 9 receptor pseudogene 1.” phenotype/function. In the absence of demonstrated func- e) Genes encoded by the opposite (antisense) strand tion a gene may be characterized by sequence, transcription that overlap a known gene, e.g., IGF2AS “insulin- or homology.” The overwhelming majority of objects named like growth factor 2, antisense.” by HGNC are in this category. f) Transcribed but untranslated functional DNA seg- ments, e.g., XIST “X (inactive)-specific transcript.” 464 GENOMICS Vol. 79, Number 4, April 2002 Copyright © 2002 Elsevier Science (USA). All rights reserved. 0888-7543/02 $35.00 doi:10.1006/geno.2002.6748, available online at http://www.idealibrary.com on IDEAL Nomenclature g) Cellular phenotypes from which the existence of a alphabet (Appendix 2, Table 1). Note that such gene gene or genes can be inferred, e.g., LOH18CR1 “loss symbols will then appear in lists in the order of the of heterozygosity, 18, chromosomal region 1.” Latin alphabet. h) EST clusters which suggest a putative gene, e.g., e) A Greek letter prefixing a gene name must be changed C1orf1 “chromosome 1 open reading frame 1.” to its Latin alphabet equivalent and placed at the end i) Fragments of expressed sequence will be designated of the gene symbol. This permits alphabetical order- a D-number by GDB (The Genome Database), e.g., ing of the gene in listings with similar properties, such DXYS155E (Appendix 1). as substrate specificities, e.g., GLA “galactosidase, ␣”; j) Polycistronic genes generated from a single mRNA, GLB “galactosidase, ␤.” but with independent coding sequence, physically f) No punctuation may be used, with the exception of separable and non-overlapping with other coding the HLA, immunoglobulin, and T-cell receptor gene sequence giving independent gene products, e.g., symbols (which may be hyphenated). The HLA sym- SNURF “SNRPN upstream reading frame” and bols are assigned by the WHO Nomenclature SNRPN “small nuclear ribonucleoprotein polypep- Committee for Factors of the HLA System [9] via the tide N.” IMGT/HLA database [10]. The immunoglobulin and k) Genes of unknown function which share highly sim- T-cell receptor gene symbols are assigned by the ilar sequences, e.g., FAM7A1 “family with sequence IMGT Nomenclature Committee via the IMGT/LIGM similarity 7, member A1,” etc. database [11]. l) Predicted (in silico) genes which show a high degree g) Gene symbols will not usually be assigned to alter- of sequence homology to well-characterized genes native transcripts. However, if a community working will be assigned the same symbol with an “L” for like, on a group of genes has a need for nomenclature e.g., TCP10L “t-complex 10 (mouse)-like.” where there are multiple small coding sequences m)Intronic transcripts (on the same DNA strand) will be which can be combined to form a number of different assigned separate symbols, usually relating to the larger products, then these coding sequences may be gene in which they reside, e.g., COPG2IT1 “coatomer assigned symbols, e.g., UGT1A1 “UDP glycosyltrans- protein complex, subunit g 2, intronic transcript 1.” ferase 1 family, polypeptide A1” to UGT1A13 repre- Gene symbols will not usually be assigned to alternative senting 13 distinct gene symbols. transcripts or to genes predicted solely from in silico data h) Tissue specificity or molecular weight should be (with no other supporting evidence, e.g., significant homol- avoided; where necessary this may be included in the ogy to a characterized gene). gene name. i) Some letters or combination of letters are used as pre- fixes or suffixes in a symbol to give a specific mean- 2. GENE SYMBOLS ing and their use for other meanings should be avoided (Section 10). Human gene symbols are designated by upper-case Latin let- j) Oncogenes are given symbols corresponding to the ters or by a combination of upper-case letters and Arabic homologous retroviral oncogene, but without the “v- numerals, with the exception of the C#orf# symbols. Symbols ” or “c-” prefixes, e.g., JUN “v-jun sarcoma virus 17 should be short in order to be useful, and should not attempt oncogene homolog (avian),” and SRC “v-src sarcoma to represent all known information about a gene [8]. Symbols (Schmidt-Ruppin A-2) viral oncogene homolog should be inoffensive and should not spell words or match (avian).” abbreviations that would cause problems with database searching, e.g., DNA. Ideally, symbols should be no longer than six characters in length. New symbols must not duplicate 3. GENE NAMES existing approved gene symbols in either the human (Genew: Human Gene Nomenclature Database) or the mouse (MGD) Gene names should be brief and specific and should convey the databases. character or function of the gene, but should not attempt to a) The initial character of the symbol should always be describe everything known about it. The first letter of the sym- a letter. Subsequent characters may be other letters, bol should be the same as that of the name in order to facilitate or if necessary, Arabic numerals. alphabetical listing and grouping. Gene names are written using b) All characters of the symbol should be written on the American spelling. Tissue specificity and molecular weight des- same line; no superscripts or subscripts may be used. ignations should be avoided as they have only limited use as a c) No Roman numerals may be used. Roman numbers description and may in time and across species prove inaccu- in previously used symbols should be changed to rate; however, they may be incorporated into the gene name if their Arabic equivalents. absolutely necessary. Gene names should not include terms d) Greek letters are not used in gene symbols. All Greek such as nephew, cousin, sister, etc.