GENES, CHROMOSOMAL REGIONS AND DEVELOPMENTAL DISORDERS

该项目的重点是基因、染色体区域、 重排和发育障碍。 删除区域 WAGR 邻近基因综合征（Wilms 瘤、无虹膜、 泌尿生殖系统异常和精神发育迟滞）是一个模型 与复杂发育相关的其他染色体区域 失调。 在这个项目中，删除区域（远端 11p12- 11p14.3) 分为多个子区间；长距离 限制和基于 YAC 的地图锚定在 HTF 岛屿上， 转录区域，并开发了 26 个重排断点； 并鉴定了许多新基因，包括肾母细胞瘤-1。 维尔姆斯瘤和无虹膜基因座都定义了新的 DNA 提供了在器官发生中具有重要作用的结合蛋白 深入了解与单倍体不足相关的基因的性质 人类畸形疾病。 然而，人们知之甚少 该综合征精神障碍的基因。它是 这里建议研究，两者都作为可能有一个基因座 大脑发育期间和候选者的基本功能 为了与该表型特征的一部分相关，另一个新的 WAGR 区域基因。 该基因编码了一个先前的 未知~古代保守~序列 - 可能是~类别标记~ 功能或建筑领域；是突出并且 主要在胎儿皮质中表达，但在成人皮质中不表达；是 新基因家族的信号成员；和端粒内的图谱 先前与精神发育迟滞相关的删除间隔 一些 WAGR 患者。 与其他连续基因一样 综合征，WAGR 相关的缺失通常很大， 包含 11p13 R 带并延伸至邻近的 G 乐队。 该地区的多面地图在这里展开， 它跨越 2 个 G/R 频带边界，提供了一个框架 研究染色体结构域的相互关系 特征、复制、转录单位和重排 断点环境。 为此，复制时序图 远端 11p12-11p14.2 将叠加并集成 WAGR区域区间、基因、HTF岛和断点 地图。 染色体缺失的形成机制 与邻近基因综合征相关的未知。 至 确定 WAGR 区域删除时的架构特征是否 断点因染色体结构域而异 它们的起始点和终止点的环境，一些 的删除边界将被克隆。

This project is focused on genes, chromosomal regions, rearrangements and developmental disorders. The deletion region of the WAGR contiguous gene syndrome (Wilms tumor, aniridia, genitourinary anomalies and mental retardation ) is a model for other chromosomal areas associated with complex developmental disorders. In this project, the deletion region (distal 11p12- 11p14.3) was divided into multiple subintervals; a long range restriction and YAC based map anchored at HTF islands, transcribed regions, and 26 rearrangement breakpoints developed; and a number of new genes identified, including Wilms tumor-1. That both the Wilms tumor and aniridia loci defined new DNA binding proteins with important roles in organogenesis provided insight into the nature of genes associated with haplo-insufficiency malformation disorders in man. Little is known, however, of the genes underlying the mental impairment of the syndrome. It is here proposed to study, both as a locus likely to have a fundamental function during brain development and as a candidate for association with part of this phenotypic feature, another new WAGR region gene. This gene encodes a previously unknown~ancient conserved~ sequence - likely a ~class marking~ functional or architectural domain; is prominently and predominantly expressed in fetal, but not adult cortex; is the signal member of a new gene family; and maps within a telomeric deletion interval previously associated with the mental retardation of some WAGR patients. As with other contiguous gene syndromes, WAGR associated deletions are frequently large, encompassing the 11p13 R band with extension into adjacent G bands. The multifaceted map of this region developed here, which crosses 2 G/R band boundaries, provides a framework for investigating the interrelationships of chromosomal domain features, replication, transcription units and rearrangement breakpoint environments. To this end, a replication timing map of distal 11p12-11p14.2 is to be superimposed on and integrated with the WAGR region interval,, gene, HTF island and breakpoint map. The mechanisms of formation of chromosome deletions associated with contiguous genes syndromes are unknown. To determine whether architectural features at WAGR region deletion breakpoints differ depending on the chromosomal domain environments of their initiation and termination points, a number of deletion boundaries will be cloned.