Next-generation sequencing of the human olfactory receptors

Humans have approximately 400 intact olfactory receptors (ORs). Among this set there are a large number of variations between individuals, a subset of which affects receptor function and can lead to interindividual variation in olfactory perception. Technological progress and cost erosion in next-generation sequencing have given us the opportunity to determine the sequence of the entire OR gene set with high fidelity and to measure the extent of variation in this functional module across many individuals. Given that whole genome sequencing remains prohibitively expensive for this purpose, especially since the OR sub-genome represents only ~0.0125 % of the human genome, we have designed a targeted capture method to enrich the OR for next-generation sequencing, which we describe here. Using this method we have been able to sequence an individual's OR sub-genome with high coverage, enabling us to identify variation with high sensitivity and specificity. This method can be used to accurate assess the amount of variability in this module and to identify the functional role of individual ORs in olfactory perception.