CONSTRUCTION OF A GENETIC LINKAGE MAP OF ZEBRAFISH

斑马鱼遗传连锁图谱的构建

• 批准号: 2284142
• 负责人: HOWARD J JACOB
• 金额: $ 30.99万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2284142
• 关键词: animal genetic material tag; biomedical resource; computer assisted sequence analysis; genetic library; genetic markers; genetic registry /resource /referral center; genotype; linkage mapping; nucleic acid hybridization; nucleic acid sequence; polymerase chain reaction; restriction fragment length polymorphism; zebrafish

Vertebrate embryologists and developmental biologists are becoming increasingly interested in a new model system, the zebrafish, Brachydanio rerio. The interest in zebrafish is derived from its value as both a genetic and embryological organism. It is ideal for genetics because the animals are small, hardy and easy to raise in large numbers because: the females lay 100-200 eggs each spawning, which can occur 1-2 times per week, and techniques for mutagenesis and transgenesis have been well- defined. For embryological studies, their advantage is that fertilization is external, and the embryos are nearly transparent, so that the migration of cells and the earliest stages of organogenesis can be directly observed. Many mutant fish have been isolated after using chemical, radiation, or insertional mutagenesis, and at least three mutagenesis screens are currently underway with the goal of reaching saturation within the next few years. The zebrafish is the only vertebrate with these advantages. Specifically we propose to: l) Construct the first complete genetic linkage map of the zebrafish. Our goal is to have a map with at least a 10 cM resolution. 2) Develop a reference cross (1000 zebrafish), and map this cross. This reference cross is essential for initiating fine structure mapping, and facilitating positional cloning. The reference cross will be made available to the entire zebrafish community. 3) Establish a means of resource distribution, insuring marker information is accessible to investigators, and that DNA from the reference cross is easily obtainable. What would the map provide and is this the time to invest in building a genetic linkage map in zebrafish? A map would 1) allow synteny conservation mapping; 2) allow complete integration of a single map, and reference cross for mutations discovered by the zebrafish community; and 3) build the foundation for gene identification and positional cloning. The zebrafish field is rapidly expanding, and there are hundreds of investigators now working on zebrafish and specific zebrafish mutations. If map construction is delayed, not only will funds be expended by several laboratories to make rudimentary independent maps of specific regions, but funds will also have to be allocated to integrate the various "local" maps. For these reasons, and after discussion, the largest zebrafish facilities decided to focus on construction of genetic linkage map using simple sequence length polymorphisms (SSLPs) at the MGH. It is for this reason funds are requested.

脊椎动物胚胎学家和发育生物学家 对一种新的模式系统，斑马鱼，Brachydanio， 雷里奥。对斑马鱼的兴趣来自于它的价值， 遗传和胚胎有机体。它是遗传学的理想选择，因为 动物小，哈代，易于大量饲养，因为： 雌鱼每次产卵100-200粒，每次产卵1-2次。 周，诱变和转基因技术已经很好- 定义了对于胚胎学研究来说，它们的优势在于 是外部的，胚胎几乎是透明的，因此迁移是可能的。 细胞和器官形成的最早阶段可以直接 观察许多变异鱼在使用化学物质后被分离出来， 辐射或插入诱变，以及至少三种诱变 屏幕目前正在进行中，目标是在 未来几年斑马鱼是唯一一种拥有这些 优势 具体而言，我们建议：1）构建第一个完整的遗传 斑马鱼的连锁图谱。我们的目标是有一个地图，至少有10 cM分辨率。2)开发一个参考交叉（1000条斑马鱼），并绘制此图 十字架这个参考交叉对于启动精细结构是必不可少的 作图和促进定位克隆。参考交叉将是 提供给整个斑马鱼社区。3)建立一种手段， 资源分配，确保标记信息可访问 研究人员，和DNA的参考交叉是很容易获得的。 地图会提供什么，现在是投资建设一个 斑马鱼的遗传连锁图一个地图将允许共线性 保护性作图; 2）允许单个图的完全整合，以及 斑马鱼群体发现的突变的参考交叉;以及 3)为基因鉴定和定位克隆奠定基础。 斑马鱼领域正在迅速扩大， 研究人员正在研究斑马鱼和特定的斑马鱼突变。 如果地图建设被推迟，不仅资金将被几个 实验室制作特定地区的基本独立地图，但 还必须拨出资金，以整合各种“地方” 地图由于这些原因，经过讨论，最大的斑马鱼 研究机构决定， MGH的简单序列长度多态性（SSLP）。正是由于这个 要求资金的原因。