Collaborative Research: The Genetic and Anatomical Determinants of Olfaction

合作研究：嗅觉的遗传和解剖学决定因素

• 批准号: 1457106
• 负责人: Robert Wayne
• 金额: $ 48.19万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1457106&HistoricalAwards=false
• 关键词: Collaborative; Research; Genetic; Anatomical; Determinants

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).

嗅觉是脊椎动物最古老的感官，但它仍然是最不了解的。在人类中，它通常被认为是一种不如视觉或听觉重要的感觉，这可能部分解释了为什么研究落后于其他感官。然而，气味检测是动物的一种基本感觉，涉及食物获取，空间定位和交配。动物嗅觉的广泛变化（从能力非常有限的海洋哺乳动物到嗅觉灵敏的物种，如狗）受到解剖学差异的影响，可能具有遗传基础，但解剖学，遗传变异，基因表达和气味检测之间的机械联系知之甚少。本计画以狗为模型系统，探讨嗅觉侦测的解剖学与遗传学。许多狗品种，如气味猎犬，已被强烈选择为增强嗅觉，而其他品种，如视力猎犬，已被选择为视觉敏锐度，并可能具有减弱的嗅觉能力。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，家犬在气味检测方面提供了独特的长期实验，并提供了在任何其他哺乳动物物种中未发现的一系列感官变化。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障碍带来新的生物医学见解。在这个项目中，犬嗅觉库，其中包括1178嗅觉受体基因的完整序列，加上基因表达的分析，将在约400只狗从26个品种的不同嗅觉能力进行。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，基因转录物的测序（RNA-seq）将基于嗅觉组织样本。这些遗传信息将补充来自相同品种的66只狗的解剖和功能分析，使用高分辨率CT扫描，这将有助于重建嗅觉器官，这将被分析并与嗅觉敏感性和嗅觉基因库多样性指数相关。在解剖学上准确的鼻腔重建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，以确定一些狗的鼻解剖结构和架构是否将更多的气味负载气流引导到鼻子的嗅觉区域。解剖学、基因组学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）。