MOLECULAR GENETIC STUDY OF THE CRI DU CHAT SYNDROME

聊天综合症的分子遗传学研究

• 批准号: 3315745
• 负责人: JOHN J WASMUTH
• 金额: $ 15.02万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3315745
• 关键词: RNA biosynthesis; cell transformation; chromosome disorders; cri du chat syndrome; cytogenetics; disease /disorder model; genetic disorder diagnosis; genetic library; genetic manipulation; genetic mapping; genetic markers; genetic models; genetic recombination; hamsters; heterozygote; human population genetics; human tissue; hybrid cells; mental retardation; messenger RNA; molecular pathology; nucleic acid hybridization; nucleic acid probes; nucleic acid sequence

This project focuses on a DNA-level analysis of the short arm of human chromosome 5 (5p), rearrangements of which are associated with the most common human deletion syndrome, cri du chat. One long term objective is to understand the molecular mechanisms involved in generating chromosomal rearrangements in germline cells and to determine if and why certain regions of the genome are particularly susceptible to rearrangement in cells undergoing meiosis. Another long range goal is to elucidate the nature and function of genes that are involved in producing the pathologies associated with cri du chat when they are rendered hemizygous by deletion. These problems are being addressed using a combination of somatic cell genetic and recombinant DNA techniques, which have provided the means to derive an accurate physical map of 5p and to delineate a small region near the end of 5p that can be considered as the pathological segment or critical region for cri du chat. Higer resolution physical and genetic maps of 5p will be compiled and will provide the starting points for cloning and analyzing chromosome breakpoint junctions in detail and for identifying functional genes within the cri du chat critical region. Furthermore, the high resolution maps of 5p will, in themselves, be valuable in addressing basic questions concerning the relationships between DNA content, cytogenetic length and genetic distance and how the relationships can vary over the length of a chromosome. The methods in place for analyzing 5p and the cri du chat syndrome at the molecular level provide an excellent model system for gaining insight into a complex genetic disorder and for addressing basic questions related to chromosome instability and rearrangement.

这个项目的重点是dna水平的分析短臂