Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping

As currently being performed with an increasing number of superfamilies, a standardized gene nomenclature system is proposed here, based on divergent evolution, using multiple alignment analysis of all 86 eukaryotic aldehyde dehydrogenase (ALDH) amino-acid sequences known at this time. The ALDHs rep resent a superfamily of NAD(P)(+)-dependent enzymes having similar primary structures that oxidize a wide spectrum of endogenous and exogenous aliphat ic and aromatic aldehydes, To date, a total of 54 animal, 15 plant, 14 yeas t, and three fungal ALDH genes or cDNAs hare been sequenced, These ALDHs ca n be divided into a total of 18 families (comprising 37 subfamilies), and a ll nonhuman ALDH genes are named here after the established human ALDH gene s, when possible. An ALDH protein from one gene family is defined as having approximately less than or equal to 40% amino-acid identity to that from a nother family. Two members of the same subfamily exhibit approximately grea ter than or equal to 60% amino-acid identity and are expected to be located at the same subchromosomal site, For naming each gene, it is proposed that the root symbol 'ALDH' denoting 'aldehyde dehydrogenase' be followed by an Arabic number representing the family and, when needed, a letter designati ng the subfamily and an Arabic number denoting the individual gene within t he subfamily; all letters are capitalized in all mammals except mouse and f ruit fly, e.g. 'human ALDH3A1 (mouse, Drosophila Aldh3a1),' It is suggested that the Human Gene Nomenclature Guidelines (http://www.gene.ucl.ac.uk/nom enclature/guidelines.html) be used for all species other than mouse and Dro sophila. Following these guidelines, the gene is italicized, whereas the co rresponding cDNA, mRNA, protein or enzyme activity is written with upper-ca se letters and without italics, e.g. 'human, mouse or Drosophila ALDH3A1 cD NA, mRNA, or activity'. If an orthologous gene between species cannot be id entified with certainty, sequential naming of these genes will be carried o ut in chronological order as they are reported to us. In addition, 20 human ALDH variant alleles that have been reported to date are listed herein and are recommended to be given numbers (or a number plus a capital letter) fo llowing an asterisk (e.g. 'ALDH3A2*2, ALDH2*4C'). It is anticipated that th is eukaryotic ALDH gene nomenclature system will be extended to include bac terial genes within the next 2 years and that this nomenclature system will require updating on a regular basis; an ALDH Web site has been established for this purpose (http://www.uchsc.edu/sp./sp./alcdbase/aldhcov.html) and will serve as a medium for interaction amongst colleagues in this held. Pha rmacogenetics 9:421-434 (C) 1999 Lippincott Williams & Wilkins.