Collaborative Research: The Genetic and Anatomical Determinants of Olfaction

嗅觉是脊椎动物最古老的感觉，但它仍然是最不为人所知的。在人类中，它通常被认为是一种不如视觉或听觉那么重要的感觉，这可能在一定程度上解释了为什么研究落后于其他感官。然而，嗅觉是动物在食物获取、空间定位和交配中的一种基本感觉。动物嗅觉的广泛差异(从能力非常有限的海洋哺乳动物到嗅觉敏锐的物种，如狗)受到解剖差异的影响，可能有遗传基础，但解剖、遗传变异、基因表达和气味检测之间的机制联系却鲜为人知。这个项目使用狗作为模型系统来研究气味检测的解剖学和遗传学。许多品种的狗，如嗅探犬，被强烈选择为具有更强的嗅觉，而其他品种，如视线犬，被选择为视觉敏锐度，可能具有减弱的嗅觉能力。其他犬类，如短面犬种，呼吸和流经鼻道的气流受损，这可能会影响它们的嗅觉。因此，家犬在嗅觉检测方面提供了一种独特的长期实验，并提供了其他任何哺乳动物物种所没有的一系列感觉变化。这些结果将揭示动物嗅觉增强或减弱的机制，并可能允许在特定的生态环境中预测感觉功能。此外，这一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个不同嗅觉能力的品种的约400只狗进行包括1178个嗅觉受体基因在内的犬类嗅觉谱系的全序列，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(RNA-seq)的测序将基于嗅觉组织样本。这些遗传信息将补充使用高分辨率CT扫描对来自同一品种的66只狗进行的解剖和功能分析，这将有助于嗅觉器官的重建，这些嗅觉器官将被分析并与嗅觉敏感度和嗅觉基因谱系多样性指数相关联。在解剖上准确重建鼻腔的气流和气味沉积的计算流体动力学模拟将在这些品种之间进行比较，以确定一些狗的鼻部解剖和结构是否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计划网站上提供，或提交到公共数据库(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).