Function of Genes in Williams Syndrome Deletion Region

描述(由申请人提供)：人类基因组计划承诺 在不久的将来提供所有人类基因的目录，主要挑战是 下个世纪的研究是功能基因组学。这一过程 在发育阶段和细胞类型中控制基因的激活和抑制 具体方式是理解正常发展和 发现人类疾病的原因。自发性复发性微缺失 是系统研究半合子效应下游影响的理想选择 在缺失中定义的一组基因。威廉姆斯-博伦综合征(WBS) 认知和行为特征明显的神经发育障碍 FEATURES作为一个模型系统来研究遗传和分子基础 认知、言语、语言和视觉空间处理。WBS由以下原因引起 染色体7q11.23的1.6Mb DNA重复一致缺失， 由侧翼重复的染色体间或染色体内重组引起 地区。在缺失中，已鉴定和鉴定了16个基因。 它们作为转录因子，在DNA复制、染色质组装、 翻译、信号转导和作为结构蛋白。只有一个，就是 弹性蛋白基因已经与一种特殊的表现--瓣膜上主动脉联系在一起 狭窄。评估半合子对另一方的功能影响 基因，部分缺失的人类将被识别和小鼠模型 在保守的共线区域中产生相应的缺失 小鼠染色体5.转录因子和信号转导的靶基因 分子将通过比较基因表达的微阵列研究来识别 在受影响的人和缺失小鼠的各种组织中的模式。发展 WBS的一种分子表型将认知神经科学与分子联系起来 遗传学。对分子途径的洞察，这导致了 染色体缺失对特定认知、行为和学习的影响 残疾可能与常见的发育障碍有关，例如 注意力缺陷/多动障碍和自闭症，以及 了解正常的发育过程。

DESCRIPTION (provided by applicant): With the Human Genome Project promising to provide a catalog of all human genes in the near future, the main challenge of research in the next century is that of functional genomics. The processes that control gene activation and repression in a developmental-stage and cell-type specific manner are fundamental to understanding normal development and discovering the causes of human disease. Spontaneously recurring microdeletions are ideal for a systematic study of the downstream effects of hemizygosity for the defined set of genes in the deletion. Williams-Beuren syndrome (WBS), a neurodevelopmental disorder with a distinct profile of cognitive and behavioral features serves as a model system to study the genetic and molecular basis of cognition, speech, language, and visuo-spatial processing. WBS is caused by recurrent uniform deletions of 1.6 Mb of DNA from chromosome 7q11.23, that arise by inter- or intrachromosomal recombination between flanking duplicated regions. Within the deletion, 16 genes have been identified and characterized. They function as transcription factors, in DNA replication, chromatin assembly, translation, signal transduction and as structural proteins. Only one, the elastin gene has been linked to a specific manifestation, supravalvular aortic stenosis. To evaluate the functional consequences of hemizygosity for the other genes, humans with partial deletions will be identified and mouse models generated with corresponding deletions in the conserved syntenic region on mouse chromosome 5. Target genes of transcription factors and signaling molecules will be identified by microarray studies, comparing gene expression patterns in various tissues from affected humans and deletion mice. Development of a molecular phenotype of WBS links cognitive neuroscience to molecular genetics. Insights gained into the molecular pathways, that lead from the chromosomal deletion to the specific cognitive, behavioral and learning disabilities may have relevance for common developmental disorders, such as attention deficit/hyperactivity disorder and autism, as well as for understanding normal developmental processes.