GENES, CHROMOSOMAL REGIONS AND DEVELOPMENTAL DISORDERS

这个项目的重点是基因，染色体区域， 重排和发育障碍。 述删除区域 WAGR邻接基因综合征（Wilms肿瘤，无虹膜， 泌尿生殖系统异常和智力迟钝）是一个模型， 与复杂发育相关的其他染色体区域 紊乱 在本项目中，缺失区（远端11 p12- 11p14.3）分为多个子区间; 限制和YAC为基础的地图锚定在HTF岛屿， 转录区，26重排断点开发; 并发现了一些新的基因，包括Wilms tumor-1。 肾母细胞瘤和无虹膜基因都定义了新的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 然而，对于人类的畸形疾病， 这种综合症的精神损害基因。是 这里提出研究，作为一个位点可能有一个 在大脑发育过程中的基本功能， 与这种表型特征的一部分相关，另一个新的 WAGR区基因。 该基因编码一种以前 未知~古老保守~序列-可能是~类标记~ 功能或建筑领域;是突出的， 主要表达于胎儿皮质，但不表达于成人皮质; 一个新基因家族的信号成员;并在端粒内作图 先前与精神发育迟滞相关的缺失间隔 一些WAGR患者。 与其他相邻基因一样， 综合征，WAGR相关缺失通常很大， 包括11 p13 R带，并延伸到相邻的G 乐队. 在这里绘制的这一地区的多面地图， 它跨越了2个G/R频段的界限，为以下方面提供了一个框架： 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， 远端11 p12 -11p14.2将叠加并与 WAGR区域间隔、基因、HTF岛和断裂点 地图 染色体缺失的形成机制 与邻近基因综合征相关的基因尚不清楚。 到 确定是否在WAGR区域删除建筑特征 断裂点因染色体结构域而异 环境的起始点和终止点，一些 将克隆删除边界。

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.