GENETIC EPIDEMIOLOGY OF THE FMR-1 GENE

FMR-1 基因的遗传流行病学

• 批准号: 2202269
• 负责人: Stephanie L. Sherman
• 金额: $ 38.03万
• 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 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2202269
• 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 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.

脆性 X [fra(X)] 综合征是最常见的形式 遗传性精神发育迟滞是最普遍的遗传性精神发育迟滞之一 已知的遗传病。这其中许多有趣的方面之一 综合征是表型异质性的显着程度 它是相关联的。广泛的认知和 行为功能尤其令人印象深刻；然而， 这种变化的基础尚未确定。最近， fra(X) 综合征被发现是由于 5'非转录区域中发现的 CGG 三联体重复序列的数量 fra(X) 精神发育迟滞-1 基因 (FMR-1)。 fra(X)的研究 家族表明该区域在减数分裂期间不稳定； 然而，影响这种不稳定的因素尚不清楚。 该项目的目的是研究 学龄、特殊需要人群中的 FMR-1 基因，以便 测试涉及流行病的三个具体假设 fra(X) 突变，FMR-1 基因型与 表型和导致临床的突变率 表达综合症。本研究的目标研究人群 独特的。首先，有特殊教育需要的儿童 携带 fra(X) 突变的风险比一般人更高 人口;然而，他们不是临床转诊人群。 因此，我们可以预期有足够的样本量作为基础 基因型-表型分析，并确保表型 不会偏向 fra(X) 综合征的特征。 其次，对确定的受试者和家庭进行直接评估 成员是可能的，因为这不是匿名样本。数据 从这些研究中收集到的信息对于研究、临床很重要 和公共卫生的立场。相关性的结果 基因型和表型之间的关系将提供有关 FMR-1 基因的正常功能可能有助于揭示 导致其他疾病的生物因素包括 认知和行为能力。的表征 FMR-1 基因在非临床参考病例中的传播 人口将提供有关潜在的假设 不稳定的生物学机制。由于现在发现了其他基因 包含相似的重复区域，从中获得的知识 研究将广泛应用于其他疾病。最后， fra(X)突变携带者患病率的评估和 表达范围是之前需要的第一步 评估 fra(X) 大规模筛选的可行性 综合症。