KARYOTYPE AND GENETIC ANALYSIS OF MENTAL RETARDATION

智力低下的核型和遗传分析

• 批准号: 6182459
• 负责人: DAVID C WARD
• 金额: $ 34.21万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182459
• 关键词: artificial chromosomes; autism; behavior test; behavioral /social science research tag; child (0-11); child mental disorders; chromosome aberrations; clinical research; cytogenetics; developmental genetics; developmental psychology; diagnosis design /evaluation; diagnosis quality /standard; fluorescent in situ hybridization; gene deletion mutation; gene expression; gene mutation; genetic disorder diagnosis; genetic mapping; human genetic material tag; human subject; karyotype; mental disorder diagnosis; mental retardation; molecular cloning; polymerase chain reaction

DESCRIPTION (Adapted from investigator's abstract): The objective of this proposal is to assess the efficacy of new fluorescence in situ hybridization techniques as adjunct diagnostic tests for pervasive developmental delay (PDD) and mental retardation (MR). In addition it is proposed to identify chromosoma loci that may harbor genes important in neural development and cognitive function. The hypothesis is that the screening of patients with PDD and/or MR with chromosome-specific painting probes, telomere-specific probe sets, and microdeletion probe sets is an effective method to identify unknown causes of PDD and MR and to identify genes involved in neurodevelopment or cognitive attributes. The investigator's laboratory currently has the capacity to produc a complete karyotype, including banding, from a signal hybridization using multicolor fluorescence in situ hybridization (M-FISH) and to test for rearrangements of telomeric and subtelomeric regions using a set of telomere-specific probes for all chromosomes except the p arms of acrocentric chromosomes. It is proposed to develop robust screening methods for karyotypic analysis, for monitoring telomere integrity and for assessing microdeletion syndrome regions using multicolor combinatorial labeled probe sets. The development of such screening methods for us in clinical cytogenetic laboratories should result in better diagnosis and prognosis assessment, and, ultimately, in better therapies for these individuals. Specifically, it is proposed to screen 300 individuals with PDD, 300 with MR, and approximately 500 normal control subjects for chromosomal abnormalities using state-of-the-art multiplex hybridization and imaging technology. The relative rates of karyotypic aberrations in these populations and the background rate of karyotypic aberrations in normal individuals will be assessed. The relative sensitivity of the new screening methods will be compared with standard cytogenetic methods. It is anticipated that this proposal will permit the investigators to make an estimate of the efficacy of karyotypic screening of patients in these diagnostic groups. In addition, specific probes will be identified that will be made available to other researchers for testing specific translocation breakpoint sites and should permit the future cloning of cDNAs that are associated with pervasive developmental delay or mental retardation.

描述（根据调查员的摘要改编）：此目的 建议是评估新荧光原位杂交的功效 技术作为普遍发育延迟的辅助诊断测试 （PDD）和智力低下（MR）。 另外，提议确定 染色体基因座可能藏有在神经发育和 认知功能。 假设是对患者的筛查 PDD和/或MR，具有特异性染色体绘画探针，端粒特异性 探针集，而微缺失探针集是一种识别的有效方法 PDD和MR的未知原因，并确定涉及的基因 神经发育或认知属性。 调查员的实验室 目前有能力生产完整的核型，包括 带有多色荧光原位的信号杂交的频带 杂交（m-fish），并测试端粒和 使用一组端粒特异性探针的亚电位区域 染色体除肢体中心染色体的P臂外。 提议 开发核型分析的强大筛选方法，用于监测 端粒完整性和用于使用微缺失综合征区域 多色组合标记的探针集。 这样的发展 我们在临床细胞遗传学实验室中为我们筛选方法应导致 在更好的诊断和预后评估中，最终以更好的方式 这些人的疗法。 具体而言，提议筛选300名PDD的人，300个 MR，大约500名染色体的正常对照受试者 使用最先进的多重杂交和成像的异常 技术。 这些核型畸变的相对速率 正常的人口和核型像差的背景率 个人将被评估。 新筛选的相对灵敏度 方法将与标准的细胞遗传学方法进行比较。 这是 预计该建议将使调查人员能够做一个 估计患者核型筛查功效 诊断组。 此外，还将确定特定的探针 将向其他研究人员提供特定的研究 易位断点站点，应允许将来克隆CDNA 与普遍的发育延迟或精神 迟钝。