GENETIC MAPPING RESOURCE FOR COMMON MAMMALIAN DISEASES

描述（由申请人提供）：伴侣动物具有遗传性人类疾病的特征；许多公司没有相应的鼠标。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，特别是猫和狗的基因组计划。针对这些物种的以生物学为重点的基因组计划将更有效地跨越小鼠和人类之间的差距。一种集中的基因定位方法将弥补这些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。它还将为全世界的研究人员提供宝贵的工具和资源。研究者的长期目标是利用伴侣动物遗传疾病的知识来深入了解人类类似疾病的发病机制。本应用程序的目的是通过使用已知具有生物学相关性的500个基因的集中定位方法来开发猫和狗的比较遗传图谱，并确定与这些基因相关的300个微卫星标记。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获得性疾病感兴趣的人类和伴侣动物研究者的研究。研究人员将通过三个具体目标来完成这项任务：1)为大约500个基因开发保守引物并筛选变异；2)鉴定每个基因的物种特异性细菌人工染色体（BAC）克隆，鉴定基因相关微卫星；3)在适当的定位资源中对基因变异和基因相关微卫星进行基因分型。由于该项目将生成比较地图，重点关注难以在人类中研究的疾病，人类健康将迅速受益于伴侣动物的生物学。在动物和人类中研究这些疾病的研究人员将在资源上有一个飞跃，包括候选基因、家族和群体关联的关联标记，以及大型插入基因组BAC克隆。这项拟议中的研究意义重大，因为它将提供一个与人类相当的三种物种的框架图，这些物种具有困扰人类的复杂和简单的疾病特征。

DESCRIPTION (provided by applicant): Companion animals have been characterized for heritable human diseases; many do not have a mouse 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. Biologically focused genome initiatives for these species would span the gap between mouse and man more efficiently. A focused gene mapping approach would remedy the smaller scale of these initiatives and allow the genomes of companion animals to unlock their biological secrets for human health and scientific advancement. It would also provide an invaluable tool and resources to researchers throughout the world. The investigator's long-range goal is to use knowledge of genetic diseases in companion animals to gain insight into the pathogenesis of comparable diseases in man. The objective of this application is to develop comparative genetic maps of the cat and dog by using a focused approach of mapping 500 genes known to have biological relevance and to identify 300 microsatellite markers associated with these genes. This focus will provide resources and facilitate the research of human and companion animal investigators who have interests in particular biological processes, simple or complex traits, and inherited or acquired diseases. The investigators will accomplish this task through three Specific Aims: 1) develop conserved primers for approximately 500 genes and screen for variation; 2) identify species-specific bacterial artificial chromosomes (BAC) clones for each gene to identify gene-associated microsatellites; and 3) gene variations and the gene-associated microsatellites will be genotyped in the appropriate mapping resources. Because this project will generate comparative maps focusing on diseases that are difficult to study in humans, 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 candidate genes, linked markers for familial and population based associations, and large insert genomic BAC clones. The proposed research is significant because it will provide a framework map comparable to humans in three species that have complex and simple disease traits that plague humans.