GENES, CHROMOSOMAL REGIONS AND DEVELOPMENTAL DISORDERS

基因、染色体区域和发育障碍

• 批准号: 2448504
• 负责人: GAIL A BRUNS
• 金额: $ 22.19万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2448504
• 关键词: Wilms' tumor; congenital eye disorder; frontal lobe /cortex; gene deletion mutation; gene expression; gene rearrangement; genetic disorder; genetic mapping; human genetic material tag; human tissue; immunocytochemistry; in situ hybridization; laboratory mouse; mental retardation; molecular cloning; molecular genetics; motor cortex; neurogenesis; reproductive system disorder; urinary tract disorder

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.

这个项目专注于基因，染色体区域，