High-resolution copy-number variation map reflects human olfactory receptor diversity and evolution.

Area of Science:

• Genomics
• Evolutionary Biology
• Human Genetics

Background:

• Olfactory receptors (ORs) are the largest mammalian protein superfamily, crucial for odorant recognition.
• Human OR gene content is reduced, with a high proportion of pseudogenes and suspected copy-number variant (CNV) involvement.

Purpose of the Study:

• To investigate the role of CNVs in the evolution of the human olfactory repertoire.
• To identify and characterize CNVs across human OR gene and pseudogene loci.

Main Methods:

• Utilized high-resolution oligonucleotide tiling microarrays to detect CNVs in 851 OR loci from 25 individuals.
• Employed quantitative PCR (qPCR) to validate microarray findings and identify additional CNVs.

Main Results:

• Identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, revealing significant inter-individual variation in OR gene dosage.
• Observed higher CNV frequency in OR pseudogenes than intact genes and an enrichment of CNVs in ORs with close human paralogs or lacking chimpanzee orthologs.
• Discovered nine common human-specific deletion alleles affecting 15 OR genes and five pseudogenes, indicating substantial human-specific alterations in OR gene content.

Conclusions:

• CNVs play a critical role in shaping the human olfactory repertoire, particularly through human-specific deletions.
• The identified deletion alleles offer potential for future genetic association studies on olfactory variation.