MOLECULAR GENETIC AND BEHAVIORAL STUDIES OF PROFOUNDLY IMPAIRED READING

阅读严重障碍的分子遗传学和行为研究

• 批准号: 7752603
• 负责人: ELENA L GRIGORENKO
• 金额: $ 16.23万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7752603
• 关键词: Address; Affect; Alleles; Architecture; Behavior; Behavior assessment; Behavioral; Candidate Disease Gene; Child; Collection; Complex; DNA; Data; Databases; Development; Environment; Environmental Risk Factor; Epidemiology; Ethnic group; Evaluation; Family; Family member; First Degree Relative; Florida; Frequencies; Genes; Genetic; Genetic Research; Genetic Variation; Haplotypes; Heritability; Hispanics; Impairment; Incidence; Individual; Investigation; Knowledge; Language; Learning; Learning Disabilities; Life; Light; Linkage Disequilibrium; Location; Measures; Minority; Molecular; Molecular Genetics; Monitor; Multivariate Analysis; Nature; Not Hispanic or Latino; Nucleic Acid Regulatory Sequences; Oral; Parents; Participant; Pattern; Performance; Phenotype; Population; Population Genetics; Population Heterogeneity; Primates; Process; Reader; Reading; Reading Disabilities; Reading Disorder; Records; Recruitment Activity; Recurrence; Relative (related person); Relative Risks; Reporting; Research; Risk; Risk Factors; Sampling; School-Age Population; Schools; Screening procedure; Services; Severities; Siblings; Single Nucleotide Polymorphism; Structure; Texture; Variant; Word Processing; Work; Writing; age related; base; disability; elementary school; ethnic minority population; experience; genetic profiling; genetic risk factor; member; novel strategies; phonology; prevent; proband; prospective; psychologic; sample collection; segregation

In this application, we propose to study behavioral profiles and genetic bases of severe reading impairment. Specifically, we will establish a unique sample of 500 severely affected elementary schools children ascertained through the PMRN database and will then recruit at least two first-degree relatives of the probands for a sample of ~1,500 individuals. We will administer a comprehensive behavioral assessment to all elementary school children and collect DNA samples from all participants. The behavioral phenotypes will be comprehensively studied, both cross-sectionally and longitudinally. In addition, we propose to conduct a relatively narrowly targeted, but in-depth, molecular-genetic study of Specific Reading Disability (SRD). Specifically, we aim to evaluate, in the newly collected PMRN database samples, the association between specific candidate genes and SRD. We propose to begin this work with a gene currently under examination, KIAA0319, and anticipate that during the life of this project there will be other candidate genes put forward through the efforts of different research groups around the world. In investigating these associations, we propose to crystallize a data-analytic approach that permits simultaneous analyses of multivariate phenotypes and multiple QTLs both cross-sectionally and longitudinally. In addition, although relatively small in magnitude, this study will offer a unique prospective on the contribution of each of the candidate genes by considering identified risk and/or protective alleles and risk and/or protective haplotypes in global genetic variation and evolutionary contexts. Specifically, the candidate genes will be investigated for ancestral alleles and haplotypes and global variation of allele and haplotype frequencies in samples from 38 world populations and a number of primate species. This in-depth analysis will permit evaluation of the frequency and structure of the candidate genes' haplotype around the world and, therefore, will increase the generalizability of results indicating the presence of association. In summary, we propose to combine behavior analyses and statistical, molecular, and population genetics in an attempt to understand associations between specific candidate genes and multiple facets of SRD in a unique, phenotypically informative, large sample of trios of first-degree relatives ascertained through probands whose severity of reading impairment puts their performance below the 3rd percentile on indicators of single-word processing.

在此应用中，我们建议研究严重阅读障碍的行为特征和遗传基础。 具体来说，我们将建立 500 名受影响严重的小学生的独特样本 通过PMRN数据库确定，然后将招募至少两名一级亲属 先证者样本约 1,500 人。我们将进行全面的行为评估 所有小学生，并收集所有参与者的 DNA 样本。行为表型将 进行横向和纵向的全面研究。此外，我们建议开展一次 针对特定阅读障碍（SRD）的相对狭窄但深入的分子遗传学研究。 具体来说，我们的目标是在新收集的 PMRN 数据库样本中评估之间的关联 特定候选基因和SRD。我们建议从目前正在检查的基因开始这项工作， KIAA0319，并预计在该项目的生命周期内还会提出其他候选基因 通过世界各地不同研究小组的努力。在调查这些协会时，我们 提出具体化一种数据分析方法，允许同时分析多变量 横截面和纵向的表型和多个QTL。另外，虽然规模相对较小 在规模上，这项研究将为每个候选基因的贡献提供独特的前景 考虑全球遗传中已识别的风险和/或保护性等位基因以及风险和/或保护性单倍型 变异和进化背景。具体来说，将研究候选基因的祖先等位基因 来自 38 个世界的样本中的单倍型以及等位基因和单倍型频率的全球变异 种群和一些灵长类物种。这种深入的分析将允许评估频率 和世界各地候选基因单倍型的结构，因此，将增加 表明关联存在的结果的普遍性。综上所述，我们建议结合 行为分析以及统计、分子和群体遗传学，试图了解 特定候选基因与 SRD 多个方面之间的关联以独特的、表型的方式 通过先证者确定的大量一级亲属三人组样本，其严重程度为 阅读障碍使他们的单字处理指标的表现低于第三百分位数。