Communicated by Richard G. H. Cotton
General Olfactory Sensitivity Database (GOSdb): Candidate Genes and their Genomic Variations
Article first published online: 11 OCT 2012
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 1, pages 32–41, January 2013
How to Cite
Keydar, I., Ben-Asher, E., Feldmesser, E., Nativ, N., Oshimoto, A., Restrepo, D., Matsunami, H., Chien, M.-S., Pinto, J. M., Gilad, Y., Olender, T. and Lancet, D. (2013), General Olfactory Sensitivity Database (GOSdb): Candidate Genes and their Genomic Variations. Hum. Mutat., 34: 32–41. doi: 10.1002/humu.22212
Contract grant sponsor: NIH (grants DC04657 and DC006070 to D.R. and A.O.); NIA (grant K23 AG036762 to J.P.); Crown Human Genome Center; ISF Legacy grant.
- Issue published online: 20 DEC 2012
- Article first published online: 11 OCT 2012
- Accepted manuscript online: 30 AUG 2012 12:00PM EST
- Manuscript Accepted: 24 AUG 2012
- Manuscript Received: 28 APR 2012
- NIH. Grant Numbers: DC04657, DC006070
- NIA. Grant Number: K23 AG036762
- Crown Human Genome Center
- ISF Legacy grant
- olfactory candidate genes;
- congenital general anosmia;
Genetic variations in olfactory receptors likely contribute to the diversity of odorant-specific sensitivity phenotypes. Our working hypothesis is that genetic variations in auxiliary olfactory genes, including those mediating transduction and sensory neuronal development, may constitute the genetic basis for general olfactory sensitivity (GOS) and congenital general anosmia (CGA). We thus performed a systematic exploration for auxiliary olfactory genes and their documented variation. This included a literature survey, seeking relevant functional in vitro studies, mouse gene knockouts and human disorders with olfactory phenotypes, as well as data mining in published transcriptome and proteome data for genes expressed in olfactory tissues. In addition, we performed next-generation transcriptome sequencing (RNA-seq) of human olfactory epithelium and mouse olfactory epithelium and bulb, so as to identify sensory-enriched transcripts. Employing a global score system based on attributes of the 11 data sources utilized, we identified a list of 1,680 candidate auxiliary olfactory genes, of which 450 are shortlisted as having higher probability of a functional role. For the top-scoring 136 genes, we identified genomic variants (probably damaging single nucleotide polymorphisms, indels, and copy number deletions) gleaned from public variation repositories. This database of genes and their variants should assist in rationalizing the great interindividual variation in human overall olfactory sensitivity (http://genome.weizmann.ac.il/GOSdb).