Genetic Mapping Resources for Common Mammalian Diseases

描述(申请人提供)：伴侣动物有许多在人类中发现的可遗传疾病；许多没有与之对应的老鼠模型。为了弥合人类和老鼠生物学之间的差距，已经启动了针对伴侣动物的基因组计划，特别是针对猫和狗的基因组计划；然而，针对猫的倡议仍然不够。一项针对猫的生物基因组计划将更有效地弥合老鼠和人之间的差距。一种有重点的基因图谱方法将弥补猫基因组计划规模较小的问题，并允许同伴动物的基因组为人类健康和科学进步揭开它们的生物秘密，为世界各地的研究人员提供宝贵的工具和资源。我们的长期目标是利用同伴动物，特别是猫的遗传病知识，深入了解人类类似疾病的发病机制。本次应用的目的是通过三个不同的研究领域来改良家猫的遗传资源。这一重点将提供资源并促进对特定生物过程、简单或复杂特征以及遗传或后天疾病感兴趣的人类和同伴动物研究人员的研究。我们将通过三个具体目标来完成这项任务：1)使用一种有重点的方法来绘制一份定义明确的猫的遗传图谱，该图谱包括500个微卫星和15,000个与致病基因相关的SNP，这些基因填补了标记覆盖率较低的区域，并定义了染色体上的进化断点。2)通过加州大学戴维斯分校兽医教学医院的动物医院服务，积极寻找新的人类疾病模型，并扩大现有的猫科动物模型。3)建立猫的表型和健康信息登记系统，收集猫的健康数据并为同一只猫提供DNA资源。该项目具有重要意义，因为它将产生关注人类难以研究的疾病的遗传资源和模型，因此，人类健康将迅速从同伴动物的生物学中受益。在动物和人类身上研究这些疾病的研究人员将在包括标志物、DNA和患者在内的资源上实现飞跃。这项拟议的研究意义重大，因为它将为单基因研究提供足够的资源，并开始收集标志物、DNA和动物，用于复杂疾病的研究，如哮喘、心脏病、糖尿病、传染病易感性和肥胖症。 公共卫生相关性(由申请者提供)：猫的生活方式已经演变为久坐不动和室内生活，模仿人类和相关的健康问题，如糖尿病、肥胖症和哮喘。拟议的资源开发将加强对人类疾病猫科动物模型的研究，支持兽医界基于临床和实验室的研究和教学，并支持向资助机构和NIH开发赠款申请。

DESCRIPTION (provided by applicant): Companion animals have many heritable diseases found in humans; many do not have a mouse model counterpart. To bridge the gap between human and mouse biology, genome projects have been initiated for companion animals, particularly for the cat and the dog; however, the initiative for the cat is still insufficient. A biologically focused genome initiative for the cat would span the gap between mouse and man more efficiently. A focused gene mapping approach would remedy the smaller scale of the cat genome project and allow the genomes of companion animals to unlock their biological secrets for human health and scientific advancement, providing invaluable tools and resources to researchers throughout the world. Our long-range goal is to use knowledge of genetic diseases in companion animals, particularly the cat, to gain insight into the pathogenesis of comparable diseases in man. The objective of this application is to improve the genetic resources for the domestic cat by three different research areas. This focus will provide resources and facilitate the research in humans and companion animal investigators who have interest in particular biological processes, simple or complex traits and inherited or acquired diseases. We will accomplish this task through three specific aims: 1) Develop a well-defined genetic map of the cat using a focused approach of mapping 500 microsatellites and -15,000 SNPs that are associated with disease causing genes, that fill areas of poor marker coverage and that define evolutionary breakpoints on the chromosomes. 2) Aggressively identify new models and augment current feline models of human disease through the animal hospital services at the UC Davis Veterinary Medicine Teaching Hospital. 3) Develop a cat phenotypic and health information registry that will collect cat health data and provide DNA resources for the same cats. The project is relevant as it will generate genetic resources and models focusing on diseases that are difficult to study in humans, therefore, human health will rapidly benefit from the biology of companion animals. Researchers studying these diseases in animals and humans will have a leap in resources, including markers, DNA and patients. The proposed research is significant because it will provide sufficient resources for single gene studies, and begin the collection of markers, DNA, and animals for complex disease studies, such as asthma, cardiac disease, diabetes, infectious disease susceptibility and obesity. PUBLIC HEALTH RELEVANCE (provided by applicant): The cat lifestyle has evolved to be sedentary and indoor, mimicking humans and associated health issues such as diabetes, obesity, and asthma. The proposed resource development will augment research for feline models of human disease, support clinical and laboratory based research and teaching within the veterinary community, and support the development of grant applications to funding agencies and the NIH.