GENETIC EPIDEMIOLOGY OF THE FMR-1 GENE

FMR-1 基因的遗传流行病学

• 批准号: 2673706
• 负责人: Stephanie L. Sherman
• 金额: $ 27.52万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-05 至 2000-04-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673706
• 关键词: alleles; child (0-11); child behavior disorders; child mental disorders; disease carrier state; epidemiology; family genetics; fragile X syndromes; gene expression; gene frequency; gene mutation; genetic carriers; genetic disorder diagnosis; genetic markers; genotype; human genetic material tag; human population genetics; human subject; interview; neuropsychological tests; phenotype; polymerase chain reaction; psychometrics

The fragile X [fra(X)] syndrome is the most common form of inherited mental retardation and one of the most prevalent of all known genetic diseases. One of the many intriguing aspects of this syndrome is the significant degree of phenotypic heterogeneity with which it is associated. The wide spectrum of cognitive and behavioral functioning is particularly impressive; however, the basis for this variability has not yet been identified. Recently, the fra(X) syndrome has been found to be the result of an increased number of CGG triplet repeats found in the 5' untranscribed region of the fra(X) mental retardation-1 gene (FMR-1). Studies of fra(X) families have shown that this region is unstable during meiosis; however, factors affecting this instability are unknown. The purpose of this project is to examine the characteristics of the FMR-1 gene in a school-aged, special needs population in order to test three specific hypotheses involving the prevalence of the fra(X) mutation, the correlation between the FMR-1 genotype and phenotype, and the mutation rates that lead to the clinically expressed syndrome. The targeted study population make this study unique. First, children with special educational needs are at higher risk for carrying the fra(X) mutation than the general population; however, they are not a clinically-referred population. Thus, we can expect adequate sample sizes on which to base genotype-phenotype analyses and also be assured that the phenotype will not be biased towards features of the fra(X) syndrome. Secondly, direct assessment of identified subjects and family members is possible since this is not an anonymous sample. The data gathered from these studies are important from a research, clinical and public health standpoint. The results from the correlation between genotype and phenotype will provide information about the normal functioning of the FMR-1 gene and may shed light on biological factors which underlie other disorders that involve cognitive and behavioral capacity. The characterization of the transmission of the FMR-1 gene in a non-clinically referred population will provide hypotheses concerning the underlying biological mechanisms of instability. As other genes are now found to contain similar repeat regions, the knowledge gained from this study will have a wide application to other disorders. Lastly, evaluation of the prevalence of fra(X) mutation carriers and the range of expression are the first steps that are needed before assessing the feasibility of mass screening for the fra(X) syndrome.

脆弱的X [fra（x）]综合征是最常见的形式 继承的智力低下，也是所有人中最普遍的之一 已知的遗传疾病。这是许多有趣的方面之一 综合征是表型异质性的重要程度 它是关联的。广泛的认知和 行为功能特别令人印象深刻。但是， 尚未确定这种变异性的基础。最近， 发现FRA（X）综合征是增加的结果 在5'未转录区域中发现的CGG三胞胎重复次数 FRA（X）心理障碍-1基因（FMR-1）的含量。 FRA的研究（x） 家庭表明，在减数分裂过程中，该地区不稳定。 但是，影响这种不稳定的因素尚不清楚。 该项目的目的是检查 在学龄前，特殊需求人群中的FMR-1基因有序 测试三个涉及流行率的特定假设 FRA（x）突变，FMR-1基因型与 表型，以及导致临床上导致的突变率 表达综合征。有针对性的研究人群使这项研究 独特的。首先，有特殊教育需求的儿童在 携带FRA（X）突变的风险高于一般 人口;但是，它们不是临床引用的人群。 因此，我们可以期望有足够的样本量以基础 基因型 - 表型分析，也可以确保表型 不会偏向FRA（X）综合征的特征。 其次，直接评估已确定的受试者和家庭 会员可能是可能的，因为这不是匿名样本。数据 从这些研究中收集的研究很重要 和公共卫生的角度。相关的结果 基因型和表型之间将提供有关 FMR-1基因的正常功能，可能会揭示 涉及其他疾病的生物因素 认知和行为能力。表征 FMR-1基因在非链式引用中的传播 人口将提供有关基础的假设 不稳定性的生物学机制。由于现在发现了其他基因 要包含类似的重复区域，从中获得的知识 研究将在其他疾病中广泛应用。最后， 评估FRA（x）突变载体的患病率和 表达范围是以前需要的第一步 评估FRA（x）的质量筛查的可行性 综合征。