HIGH THROUGHPUT FISH MAPPING

产品说明：（申请人摘要）：项目1（高重复率FISH绘图）将侧重于收集、编目和染色体断裂点绘图具有明显平衡重排和先天性异常的个体。 核型、注释的断点和临床信息将保存在DGAP数据库（http：//dgap.harvard.edu/）中。 除NIGMS人遗传突变细胞库外，还将从国家和国际临床遗传学家和临床细胞遗传学家网络获得或建立人细胞系。 使用人BAC克隆的荧光原位杂交（FISH）将用于鉴定跨越染色体断裂点的基因组片段。 为了实现高通量FISH定位，已经与“基因组社区”的成员建立了合作，这些成员已经为我们提供了人类BAC，这些BAC代表了在整个基因组中以大约1 Mb的间隔间隔分布的FISH定位克隆的集合，并与基于辐射杂交的物理图谱相关。 估计每年约有100个新的断点案例，包括存档和预期的收藏。 基于“两次命中”病例的识别（即，具有类似断点和异常的患者），并将采用生物资源优先级计划，目的是每年确定8个断点，以传递给项目2（快速基因发现）。 项目2和3（模式生物基因发育分析）的基因鉴定和表征研究将在DGAP数据库上公布。 总的来说，项目1将作为功能基因组学项目的切入点，该项目将产生对人类发育至关重要的基因的公共资源。

DESCRIPTION: (Applicant's Abstract): Project 1 (High Throughput FISH Mapping) will focus on the collection, cataloguing and chromosomal breakpoint mapping of individuals with apparently balanced rearrangements and congenital anomalies. Karyotypes, annotated breakpoints and clinical information will be deposited in the DGAP database (http://dgap.harvard.edu/). Human cell lines will be obtained or established from a national and international network of Clinical Geneticists and Clinical Cytogeneticists in addition to the NIGMS Human Genetic Mutant Cell Respository. Fluorescence in situ hybridization (FISH) using human BAC clones will be used to identify genomic segments that span chromosomal breakpoints. To accomplish high throughput FISH mapping, collaborations have been established with members of the "genome community" who are already providing us with human BACs representing a collection of FISH-mapped clones spaced at an approximately 1 Mb interval throughout the genome and correlated with radiation hybrid-based physical maps. About 100 new breakpoint cases are estimated to be accessioned per year including archived and prospective collections. A well-defined clinical prioritization scheme based on the identification of "two-hit" cases (i.e., patients with similar breakpoints and anomalies) and a biological resources prioritization plan will be employed with the aim of identifying 8 breakpoints per year to be passed to Project 2 (Rapid Gene Discovery). Gene identification and characterization studies from Projects 2 and 3 (Developmental Analysis of Genes in Model Organisms) will be posted on the DGAP database. In overview, Project 1 will serve as the entry point for a functional genomics project that will generate a public resource of genes critical in human development.