Collaborative Research: The Genetic and Anatomical Determinants of Olfaction

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The sense of smell is the oldest of the vertebrate senses and yet it remains the least understood. In humans, it is often considered a less important sense than vision or hearing, and this may explain in part why research has lagged behind that of other senses. Nevertheless, scent detection is a fundamental sense in animals involved in food acquisition, spatial orientation and mating. The wide variation of the sense of smell in animals (from marine mammals with very limited abilities to keen-scented species such as dogs) is affected by anatomical differences and likely has a genetic basis, yet the mechanistic connections between anatomy, genetic variation, gene expression and scent detection are poorly understood. This project uses dogs as a model system to investigate the anatomy and genetics of scent detection. Many dog breeds, such as scent hounds, have been strongly selected for an enhanced sense of smell, whereas other breeds, such as sight hounds, have been selected for visual acuity and are likely to have diminished ability to smell. Other canines, such as short-faced breeds, have impaired breathing and airflow across the nasal passage, which likely affects their sense of smell. Consequently, domestic dogs present a unique long-term experiment in scent detection and provide a range of sensory variation not found within any other mammal species. The results will uncover the mechanisms that enhance or lessen the sense of smell in animals and may allow for predictions of sensory function in a specific ecological context. Further, the results may lead to new biomedical insights for human health and impairments in the sense of smell. In this project, the full sequence of the canine olfactory repertoire, which includes 1178 olfactory receptor genes, coupled with an analysis of gene expression will be undertaken in about 400 dogs from 26 breeds of varying olfactory ability. The genes will be sequenced using a capture array designed from existing complete genome sequences and the sequencing of gene transcripts (RNA-seq) will be based on olfactory tissue samples. This genetic information will complement anatomical and functional analyses of 66 dogs from the same breeds using high-resolution CT scans that will facilitate reconstruction of the olfactory organ, which will be analyzed and correlated with indices of olfactory sensitivity and olfactory gene repertoire diversity. Computational fluid dynamics simulations of airflow and odorant deposition in anatomically accurate reconstructions of the nasal cavity will be compared across these breeds to determine if the nasal anatomy and architecture of some dogs directs more odorant-laden airflow to the olfactory region of the nose. Anatomical, genomic and expression data will be available on the program website or submitted to public databases (e.g. DigiMorph or Genbank).