CRI DU CHAT SYNDROME: GENE IDENTIFICATION

描述：CRI-DU-CHAT综合征是一种常见的部分性肿瘤。 由5号染色体短臂缺失引起。患有 这种综合征表现为小头畸形、圆脸、过度调理、 小下颌，突出的鼻梁，上丘皱褶，低眼压，和 严重的精神运动和精神发育迟滞。通过刻画人物形象 超过50名有5p缺失的患者，一个染色体区域有2个MBP 5p15.2和猫般的哭声所涉及的染色体片段 已将两个区域的YAC重叠群映射到750个5p15.3区域 已经确定了跨越每个区域的完整和非嵌合的YAC。 虽然这项提议的长期目标是识别基因，当 出现在一个副本中，导致与 CRI-DU-Chat综合征，最初的目标将是发展一种转录 该区域的图谱，以便根据它们的基因识别候选基因 相对于cri-du-chat关键区域的位置。该战略旨在 识别这些基因首先是继续表征 有少量5p缺失或部分CRI-DU-CHAT表型的患者 这两个关键区域可以进一步缩小。二、建设 已经启动的粘粒重叠群将完成。第三, 识别关键区域内基因定位的几种方法 包括EST作图、cDNA选择、外显子捕获和 克隆HTF岛。在执行筛选策略以确定 来自同一基因的克隆，表达模式 将对独特的基因进行研究。这项调查将包括 研究AS在成人和胎儿组织中的表达水平 以及在不同的小鼠妊娠阶段的表达水平。这个 这些基因的初步特征将确定候选基因 可能与CRI-DU-CHAT综合征的临床病因学有关 基因在胎儿发育过程中是否表达。

DESCRIPTION: The cri-du-chat syndrome is a well-described partial aneusomy resulting from the deletion of the short arm of chromosome 5. Patients with this syndrome present with microcephaly, a round face, hypertelorism, micrognathia, prominent nasal bridge, epicanthal folds, hypotonia, and severe psychomotor and mental retardation. Through the characterization of over 50 patients with 5p deletions, a chromosomal region that is 2 Mbp in 5p15.2 and the chromosomal segment involved in the cat-like cry has been mapped to a 750 region of 5p15.3 YAC contigs of both regions have been completed and nonchimeric YACS that span each region have been identified. While the long term goal of this proposal is to identify genes that, when present in one copy, cause the clinical features associated with the cri-du-chat syndrome, the initial goal will be to develop a transcriptional map of the region in order to identify candidate genes based on their location with respect to the cri-du-chat critical regions. The strategy to identify these genes is first to continue with the characterization of patients with small 5p deletions or partial cri-du-chat phenotypes such that the two critical regions can be further narrowed. Second, the construction of a cosmid contig which has been initiated will be completed. Third, several approaches to identify the genes mapping within the critical regions will be performed and include EST mapping, cDNA selection, exon-trapping and cloning HTF islands. After performing screening strategies to identify clones that are derived from the same gene, the pattern of expression of unique genes will be investigated. This investigation will include investigating the level of expression in human adult and fetal tissues as well as the level of expression in different murine gestational stages. The initial characterization of these genes will identify candidate genes that may be involved in the clinical etiology of the cri-du-chat syndrome based on whether a gene is expressed during fetal development.