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Extensive copy-number variation of the human olfactory receptor gene family.

Young, Janet M and Endicott, Raelynn M and Parghi, Sean S and Walker, Megan and Kidd, Jeffrey M and Trask, Barbara J (2008) Extensive copy-number variation of the human olfactory receptor gene family. American journal of human genetics, 83 (2). pp. 228-242. ISSN 1537-6605

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As much as a quarter of the human genome has been reported to vary in copy number between individuals, including regions containing about half of the members of the olfactory receptor (OR) gene family. We have undertaken a detailed study of copy-number variation of ORs to elucidate the selective and mechanistic forces acting on this gene family and the true impact of copy-number variation on human OR repertoires. We argue that the properties of copy-number variants (CNVs) and other sets of large genomic regions violate the assumptions of statistical methods that are commonly used in the assessment of gene enrichment. Using more appropriate methods, we provide evidence that OR enrichment in CNVs is not due to positive selection but is because of OR preponderance in segmentally duplicated regions, which are known to be frequently copy-number variable, and because purifying selection against CNVs is lower in OR-containing regions than in regions containing essential genes. We also combine multiplex ligation-dependent probe amplification (MLPA) and PCR to assay the copy numbers of 37 candidate CNV ORs in a panel of approximately 50 human individuals. We confirm copy-number variation of 18 ORs but find no variation in this human-diversity panel for 16 other ORs, highlighting the caveat that reported intervals often overrepresent true CNVs. The copy-number variation we describe is likely to underpin significant variation in olfactory abilities among human individuals. Finally, we show that both homology-based and homology-independent processes have played a recent role in remodeling the OR family.

Item Type: Article or Abstract
DOI: 10.1016/j.ajhg.2008.07.005
PubMed ID: 18674749
PMCID: PMC2495065
Keywords or MeSH Headings: Alleles Base Sequence Computational Biology/methods Gene Deletion Gene Dosage Genetic Variation* Genome, Human Humans Models, Genetic Models, Statistical Molecular Sequence Data Phenotype Receptors, Odorant/genetics* Sequence Analysis, DNA Sequence Homology, Nucleic Acid
Subjects: Cellular and Organismal Processes > Genetic processes > Mutation
Cellular and Organismal Processes > Evolution
Molecules > Proteins > Receptors
Research Methodologies > Computational Biology
Depositing User: Library Staff
Date Deposited: 23 Sep 2008 19:45
Last Modified: 14 Feb 2012 14:42

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