Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan;34(1):32-41.
doi: 10.1002/humu.22212. Epub 2012 Oct 11.

General olfactory sensitivity database (GOSdb): candidate genes and their genomic variations

Ifat Keydar  1 , Edna Ben-Asher, Ester Feldmesser, Noam Nativ, Arisa Oshimoto, Diego Restrepo, Hiroaki Matsunami, Ming-Shan Chien, Jayant M Pinto, Yoav Gilad, Tsviya Olender, Doron Lancet
Affiliations

General olfactory sensitivity database (GOSdb): candidate genes and their genomic variations

Ifat Keydar et al. Hum Mutat. 2013 Jan.

Abstract

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).

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
A: The 30 top DS6 annotated genes. These genes are differentially expressed in mouse olfactory epithelium, and also annotated in the olfactory context by other sources (DS1, 2, 3, 11). B: The 30 top DS6 novel genes. These genes are differentially expressed in mouse olfactory epithelium, but are not annotated in the olfactory context by DS1, 2, 3, 11. Genes implicated in genetic diseases include ASAH2 (MIM# 611202), associated with Alzheimer’s disease and Niemann–Pick disease, SULT6B1 associated with schizophrenia, AMBN (MIM# 601259), associated with amelogenesis imperfecta, and AMLEX (MIM# 300391) associated with amelogenesis imperfecta as well.
Figure 2
Figure 2
The relative contribution of the 3 data sources DS1-3 to the long list of 1,680 auxiliary olfactory genes. In parentheses: the number of genes that are also found differentially expressed in olfactory tissues via DS5-9.
Figure 3
Figure 3
Scores for short list genes.
Figure 4
Figure 4
Histogram of minor allele frequency for different variation types. Deleterious missense include SNPs probably damaging according to PolyPhen-2 (Score > 0.95).
See this image and copyright information in PMC

References

    1. Ahdab-Barmada M, Claassen D. A distinctive triad of malformations of the central nervous system in the Meckel–Gruber syndrome. J Neuropathol Exp Neurol. 1990;49:610–620. - PubMed
    1. Amoore JE, Steinle S. A graphic history of specific anosmia. Chem Senses. 1991;3:331–351.
    1. Atanasova B, Graux J, El Hage W, Hommet C, Camus V, Belzung C. Olfaction: a potential cognitive marker of psychiatric disorders. Neurosci Biobehav Rev. 2008;32:1315–1325. - PubMed
    1. Belluscio L, Gold GH, Nemes A, Axel R. Mice deficient in G(olf) are anosmic. Neuron. 1998;20:69–81. - PubMed
    1. Bergman JE, Bocca G, Hoefsloot LH, Meiners LC, van Ravenswaaij-Arts CM. Anosmia predicts hypogonadotropic hypogonadism in CHARGE syndrome. J Pediatr. 2010;158:474–479. - PubMed

Publication types