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Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray.

ABSTRACT: Olfactory receptor (OR) genes were discovered more than a decade ago, when Buck and Axel observed that, in rats, certain G-protein coupled receptors are expressed exclusively in the olfactory epithelium. Subsequently, protein sequence similarity was used to identify entire OR gene repertoires of a number of mammalian species, but only in mouse were these predictions followed up by expression studies in olfactory epithelium. To rectify this, we have developed a DNA microarray that contains probes for most predicted human OR loci and used that array to examine OR gene expression profiles in olfactory epithelium tissues from three individuals.We detected expression of 437 (76%) human OR genes in these olfactory epithelia. Interestingly, we detected widespread expression of OR pseudogenes, an observation that may shed light on the mechanism of OR gene choice in the olfactory sensory neurons. To address the hypothesis that OR genes may carry out additional functions, we also characterized the expression of OR genes in a number of non-olfactory tissues.While our results corroborate the functional annotation of the majority of predicted human odorant receptors, we find that a large number of putative human OR genes are expressed in non-olfactory tissues, sometimes exclusively so. Our evolutionary analysis of ectopically expressed human OR genes does not lend support to the hypothesis that these genes have alternative functions.

SUBMITTER: Zhang X

PROVIDER: S-EPMC1929152 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray.

Zhang Xiaohong X De la Cruz Omar O Pinto Jayant M JM Nicolae Dan D Firestein Stuart S Gilad Yoav Y

Genome biology 20070101 5

<h4>Background</h4>Olfactory receptor (OR) genes were discovered more than a decade ago, when Buck and Axel observed that, in rats, certain G-protein coupled receptors are expressed exclusively in the olfactory epithelium. Subsequently, protein sequence similarity was used to identify entire OR gene repertoires of a number of mammalian species, but only in mouse were these predictions followed up by expression studies in olfactory epithelium. To rectify this, we have developed a DNA microarray t ...[more]

PMID: 17509148

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Project description:Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems), containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men). Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose) were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were found in the expressed olfactory receptors gene set.

Dataset Information

Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray.

Publications

Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray.

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