X-Linked Mental Retardation-Linkage

X连锁智力低下-连锁

• 批准号: 6886823
• 负责人: Charles E Schwartz
• 金额: $ 146.04万
• 依托单位: GREENWOOD GENETIC CENTER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886823
• 关键词: behavioral /social science research tag; brain morphology; developmental neurobiology; developmental psychology; disease /disorder etiology; family genetics; functional /structural genomics; gender difference; genetic mapping; genetic markers; genetic polymorphism; genetic susceptibility; histology; human genetic material tag; human subject; magnetic resonance imaging; mental retardation; microarray technology; molecular cloning; neuropathology; neuropsychological tests; nucleic acid sequence; patient oriented research; sex linked trait

DESCRIPTION (provided by applicant): A 20 to 30 percent excess of males among the mentally retarded population is well documented. At least half of the excess is likely due to mutations of X-linked genes. An estimated 30-40 loci are associated with nonsyndromic X-linked mental retardation (XLMR) and one hundred thirty are associated with specific XLMR syndromes. The best known of these is the Fragile X syndrome but it accounts for only a third of XLMR families. Because of the X-linked mode of inheritance and current molecular methodologies, these disorders are especially amenable to study. The hypothesis to be tested is that a full understanding of the genetics and pathogenesis of these disorders will lead to improved diagnosis and (ultimately) therapy. The immediate goal of the study is to identify the causative genes and the genetic pathways leading to XLMR. In addition, we will better define the clinical and neurobehavioral phenotypes of these disorders, each of which presents unique aspects about brain development and function. Over the last ten years, 55 large XLMR families and 68 smaller families have been admitted to the study for gene localization, gene testing and neurobehavioral studies. Thirty-two of the families have been localized to a discrete region of the X chromosome. In addition to these families, 2 males with inversions of the X chromosome associated with mental retardation and 3 males with small deletions are available for molecular studies. We have deposited brains from three XLMR study families are in the Miami Brain Bank and will utilize them for both molecular studies and comprehensive histological analysis. Three new investigators, (Srivastava, Inana, and Warren) have joined the study. A variety of appropriate microarray systems, subtractive cDNA and other appropriate methods (including maximal utilization of the new human genorne data) will be used to identify and characterize ten to fifteen XLMR genes over the next five years. We will continue to admit five new families and a number of smaller families each year. Neurobehavioral studies will be closely integrated into the clinical evaluation of each of the new large families. More extensive neurobehavioral studies along with MRI morphometric analysis will be conducted in three XLMR entities: Coffin-Lowry, ATRX and Allan-Herndon Syndrome. In summary, this represents a unique study that combines a variety of methodologies and disciplines in order to better understand the role of genes on the X chromosome in brain development and function.

描述(由申请人提供)：超过20%至30%的男性 智障人口的情况是有据可查的。至少有一半的人 过量可能是由于X连锁基因的突变所致。估计有30-40个基因座 与非综合征性X-连锁精神发育迟滞(XLMR)和一种 130例与特定的XLMR综合征有关。最著名的 这就是脆性X综合征，但它只占XLMR的三分之一 家人。因为X连锁的遗传模式和当前的分子 在方法论上，这些障碍特别适合研究。假说 需要检验的是对遗传病的遗传学和发病机制的充分了解 这些疾病将导致诊断和(最终)治疗的改进。这个 这项研究的直接目标是确定致病基因和基因 通向XLMR的路径。此外，我们将更好地定义临床和 这些障碍的神经行为表型，每一种都是独一无二的 关于大脑发育和功能的方面。在过去的十年里，55个大的 XLMR家族和68个较小的家族已被纳入基因研究 定位、基因测试和神经行为研究。其中32个 家系已经被定位在X染色体的一个离散区域。在……里面 除这些家族外，还有2名男性X染色体倒位 与智力低下有关，3名男性有轻微缺失 可用于分子研究。我们已经保存了三个XLMR研究的大脑 家庭在迈阿密脑库中，并将利用它们来研究这两个分子 研究和全面的组织学分析。三名新的调查员， (Sriastava、Inana和Warren)已经加入了这项研究。各种合适的 微阵列系统、消减cDNA和其他适当的方法(包括 最大限度地利用新的人类基因组数据)将用于确定和 在接下来的五年中确定10到15个XLMR基因的特征。我们会 继续每年接纳五个新家庭和一些较小的家庭。 神经行为研究将与临床评估紧密结合。 每一个新的大家庭。更广泛的神经行为研究 通过MRI，将在三个XLMR实体中进行形态测量分析： 棺材-Lowry，ATRX和Allan-Herndon综合征。总而言之，这代表着 独一无二的研究，结合了各种方法和学科 为了更好地了解X染色体上的基因在脑发育中的作用 和功能。