Collaborative Research: The Genetic and Anatomical Determinants of Olfaction

嗅觉是脊椎动物最古老的感官，但它仍然是最不为人所知的。在人类中，它通常被认为不如视觉或听觉重要，这可能部分解释了为什么对其他感官的研究落后于其他感官。然而，气味探测是动物获取食物、空间定位和交配的基本感觉。动物（从能力非常有限的海洋哺乳动物到嗅觉敏锐的物种，如狗）嗅觉的广泛变化受到解剖学差异的影响，可能有遗传基础，但解剖学、遗传变异、基因表达和气味检测之间的机制联系尚不清楚。这个项目使用狗作为模型系统来研究嗅觉的解剖学和遗传学。许多品种的狗，如嗅觉猎犬，被强烈地选择为嗅觉增强的狗，而其他品种的狗，如视力猎犬，被选择为视觉敏锐的狗，嗅觉能力可能会减弱。其他犬科动物，如短脸犬，呼吸和鼻腔气流受损，这可能会影响它们的嗅觉。因此，家养狗在气味探测方面进行了一项独特的长期实验，并提供了一系列其他哺乳动物物种所没有的感官变化。研究结果将揭示增强或减弱动物嗅觉的机制，并可能在特定的生态环境中预测感官功能。此外，这些结果可能会为人类健康和嗅觉损伤带来新的生物医学见解。在这个项目中，将对来自26个不同嗅觉能力品种的约400只狗进行完整的嗅觉库序列，其中包括1178个嗅觉受体基因，并对基因表达进行分析。这些基因将使用从现有完整基因组序列设计的捕获阵列进行测序，基因转录本测序（RNA-seq）将基于嗅觉组织样本。这些遗传信息将补充66只来自同一品种的狗的解剖和功能分析，使用高分辨率CT扫描，将有助于嗅觉器官的重建，并将其与嗅觉敏感性和嗅觉基因库多样性指标进行分析和关联。计算流体动力学模拟的气流和气味沉积在解剖学上精确的鼻腔重建中，将在这些品种之间进行比较，以确定是否一些狗的鼻腔解剖和结构将更多的气味气流引导到鼻子的嗅觉区域。解剖、基因组和表达数据将在项目网站上提供或提交到公共数据库（例如DigiMorph或Genbank）。

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).