Genetic and genomic investigations of hereditary, viral, and parasitic wildlife diseases in non-model organisms

非模式生物遗传性、病毒性和寄生性野生动物疾病的遗传和基因组研究

• 批准号: RGPIN-2014-05265
• 负责人: Marshall, Heather
• 金额: $ 2.55万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=567054
• 关键词: Genetic; genomic; investigations; hereditary; viral

The objectives of this proposal are to elucidate genetic/genomic factors associated with wildlife diseases in wild canid models. Infectious and inherited wildlife diseases cause economic and cultural losses and pose potential health threats to humans. The red fox is a non-model organism ideally suited for molecular genetic and genomic investigations into causes and consequences of wildlife diseases. Foxes are "genomically enabled" by the available domestic dog genome assembly, providing access to genomic resources such as microarrays and candidate gene sequences. Newfoundland red foxes harbour at least three significant wildlife diseases, including hereditary, viral, and parasitic. Farmed silver foxes in Newfoundland and parts of Europe experience hereditary hyperplastic gingivitis (HHG), a gum disease that hinders breeding programs. Using canine microarrays, we (HQP and I) have identified a set of functional candidate genes in developmental genetic cell signalling pathways which we intend to characterize via candidate gene sequencing and quantitative PCR, with the objective of discovering the gene and causative mutation of this condition. Additional candidate genes will be identified and tested using linkage analyses. The only endemic focus in North America of the global endoparasitic nematode French heartworm is in Newfoundland. This infectious disease is of concern due to transmission from foxes to domestic dogs, and increasingly to coyotes, foreshadowing its possible spread to other parts of Canada. Functional genomic approaches will be used to identify correlates of successful heartworm transmission and host infection. The red fox strain of rabies virus persists in northern Canada and threatens to invade a wider geographic area, as exemplified by a mid-1950s spread throughout eastern Canada, with obvious concerns for public health. I propose to eludicate fox phylogeographic structure in northeastern Canada, using genome-wide single nucleotide polymorphisms (SNPs) to identify geographic or other barriers to viral transmission and genetic correlates of disease resistance. This research forges collaborations among Memorial University, the Fur Breeder’s Association, and Animal Health Division, and will be important to fur farmers in Canada and Europe, wildlife management officials and dog owners throughout Canada, researchers of human disease, and basic researchers of mammalian growth and development. For example, the gum overgrowth causes dental abscess and compromises feeding ability of foxes, affecting their quality of life and economic value. The Fur Breeder's Association is therefore unable to propagate foxes while the genetic cause and inheritance pattern of the gum condition, and related fur quality, are unknown. An anticipated outcome of our research is a diagnostic test of this disease. The discovery of the gene and causative mutation of HHG will also provide an entry point into the genetics of a similar human disease, especially the form characterized by hypertrichosis; by using a furbearing carnivore disease to model a human one, both human and animal health issues are addressed. The identification of pathogenic mutations of genes associated with the cell cycle will also be informative to cancer research. Understanding the nature of the hyperplasia contributes to basic knowledge about growth and development. The canine pulmonary angiostrongylus work will help develop a spatio-temporal model of parasite spread and maintenance in wild canids and contributes to understanding and prevention of further spread of this severe infection in dogs. Rabies is also a serious wildlife concern and potentially harmful to humans as well, and understanding its transmission is vital to monitoring and preventing spread of this virus.

本提案的目的是阐明野生犬科动物模型中与野生动物疾病相关的遗传/基因组因素。传染性和遗传性野生动物疾病造成经济和文化损失，并对人类的健康构成潜在威胁。红狐是一种非模式生物，非常适合于对野生动物疾病的原因和后果进行分子遗传学和基因组研究。狐狸是“基因组启用”的可用的家犬基因组组装，提供基因组资源，如微阵列和候选基因序列。纽芬兰红狐至少携带三种重要的野生动物疾病，包括遗传性、病毒性和寄生性疾病。纽芬兰和欧洲部分地区养殖的银狐患有遗传性增生性牙龈炎（HHG），这是一种阻碍繁殖计划的牙龈疾病。利用犬微阵列，我们（HQP和I）已经确定了一组在发育遗传细胞信号通路中的功能候选基因，我们打算通过候选基因测序和定量PCR来表征这些基因，目的是发现这种情况的基因和致病突变。其他候选基因将被识别并使用连锁分析进行测试。全球内寄生线虫法国心丝虫在北美唯一的地方性焦点是在纽芬兰。这种传染病令人担忧，因为它从狐狸传播给家养狗，并越来越多地传播给土狼，这预示着它可能蔓延到加拿大其他地区。功能基因组方法将用于鉴定成功的心丝虫传播和宿主感染的相关性。狂犬病毒的红狐毒株持续存在于加拿大北部，并有可能侵入更广泛的地理区域，如20世纪50年代中期在加拿大东部的传播，这显然对公共卫生造成了影响。我建议阐明加拿大东北部狐狸的系统地理结构，使用全基因组单核苷酸多态性（snp）来确定病毒传播的地理或其他障碍以及抗病的遗传相关。这项研究建立了纪念大学、毛皮育种协会和动物卫生部门之间的合作关系，对加拿大和欧洲的毛皮农民、加拿大各地的野生动物管理官员和狗主人、人类疾病研究人员以及哺乳动物生长和发育的基础研究人员都很重要。例如，牙龈过度生长导致狐狸的牙脓肿，影响狐狸的取食能力，影响狐狸的生活质量和经济价值。因此，毛皮育种协会无法繁殖狐狸，因为牙龈状况的遗传原因和遗传模式以及相关的毛皮质量都是未知的。我们研究的一个预期结果是对这种疾病的诊断测试。HHG基因和致病突变的发现也将为研究类似人类疾病的遗传学提供切入点，特别是以多毛为特征的形式；通过使用一种繁殖的食肉动物疾病来模拟人类疾病，解决了人类和动物的健康问题。鉴定与细胞周期相关的致病基因突变也将为癌症研究提供信息。了解增生的本质有助于了解生长发育的基本知识。犬肺管圆线虫的研究将有助于建立寄生虫在野生犬科动物中传播和维持的时空模型，并有助于了解和预防这种严重感染在犬中的进一步传播。狂犬病也是一个严重的野生动物问题，也可能对人类有害，了解其传播对监测和预防该病毒的传播至关重要。