Genetic Mapping Resources for Common Mammalian Diseases

描述（由申请人提供）：伴侣动物有许多人类遗传疾病；许多公司没有相应的鼠标模型。为了弥合人类和小鼠生物学之间的差距，已经启动了伴侣动物的基因组计划，特别是猫和狗；但是，对于猫的主动性还是不够。以生物学为中心的猫基因组计划将更有效地跨越老鼠和人之间的差距。集中的基因定位方法将弥补猫基因组计划规模较小的不足，并允许伴侣动物的基因组解开它们的生物秘密，以促进人类健康和科学进步，为全世界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伴侣动物，特别是猫的遗传疾病知识，深入了解人类类似疾病的发病机制。本申请的目的是通过三个不同的研究领域来改善家猫的遗传资源。这一重点将提供资源并促进对人类和伴侣动物研究者的研究，他们对特定的生物过程，简单或复杂的特征以及遗传或获得性疾病感兴趣。我们将通过三个具体目标来完成这项任务：1)利用集中的方法绘制500个微卫星和-15,000个与致病基因相关的snp的明确的猫遗传图谱，这些snp填补了标记覆盖率低的区域，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，积极识别新的模型并增强现有的人类疾病猫模型。3)开发猫表型和健康信息注册，收集猫的健康数据并提供相同猫的DNA资源。该项目具有重要意义，因为它将产生遗传资源和模型，重点关注难以在人类中研究的疾病，因此，人类健康将迅速受益于伴侣动物的生物学。在动物和人类身上研究这些疾病的研究人员将在资源上有一个飞跃，包括标志物、DNA和患者。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，并开始为复杂疾病研究收集标记物、DNA和动物，如哮喘、心脏病、糖尿病、传染病易感性和肥胖。

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.