GNAS2009 Abstract #13 - Lancet, Doron

Nomenclature for olfactory receptor

Doron Lancet, Tsviya Olender, Marilyn Safran, Arye Harel and Daniel W. Nebert*

The Crown Human Genome Center, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100 Israel and *Center for Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0056, USA

Olfactory receptors (ORs) constitute the largest gene superfamily in the mammalian genome. It encompasses 390 ostensibly functional genes and 465 pseudogenes comprising 18 gene families and ~300 gene subfamilies. In humans, OR genes are located on all chromosomes, except one autosome and the Y-chromosome. There has been a gradual evolutionary diminution of the OR repertoire en route from rodents and dog, via monkeys and apes to humans; this likely reflects the diminished behavioral requirement of the sense of smell for survival along this evolutionary axis. The nomenclature system (based on evolutionary divergence of genes into families and subfamilies of the OR gene superfamily) has been designed similarly to that originally used in the 1980s for the CYP gene superfamily (Olender, Lancet and Nebert, Hum Genomics 2008; 3: 87-97). A compendium of human OR genes and some of their orthologs is presented in HORDE, the Human Olfactory Data Explorer (http://genome.weizmann.ac.il/horde/ ). HORDE is based on HGNC nomenclature and provides information on OR proteins, their gene structure and their genomic organization, as well as a set of analysis tools. OR genes are also depicted within the gene-centric GeneCards database (http://www.genecards.org/ ), which is also strongly based on HGNC nomenclature, and places OR genes in a full genome context. GeneCards now contains a new feature, a scale of functional annotation called GIFtS (Gene Inferred Functionality Score); this is routinely used to assess needs for further annotation, which can also be useful for nomenclature establishment.

One of the important gene nomenclature challenges is strongly embodied in the OR superfamily: several dimensions of inter-individual human variability. One prominent case is the existence of up to 100 OR loci at which some human individuals have a pseudogene and others ' " an intact OR gene. One example is OR11H7P, whose HGNC symbol attests to its being a pseudogene based on the reference genome, but is now known to have an intact allele as well (Menashe et al., PLoS Biol 2007; 5: e284). This may call for another symbol, OR11H7Pv1, or perhaps the establishment of a general rule whereby a symbol such as OR11H7Q will indicate allele segregation between a gene and a pseudogene. We are currently studying extensively the occurrence of copy-number variations (CNVs) in OR genes (Hasin et al., PLoS Genet 2008; 4: e1000249), as a model for the more general hurdles posed by CNV alleles to gene nomenclature.