GENOTYPE AND PHENOTYPE ANALYSES OF FAMILIAL DYSLEXIA

家族性阅读障碍的基因型和表型分析

• 批准号: 2430877
• 负责人: BRUCE F PENNINGTON
• 金额: $ 10.13万
• 依托单位: UNIVERSITY OF DENVER (COLORADO SEMINARY)
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-01-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430877
• 关键词: adolescence (12-20); attention deficit disorder; behavioral /social science research tag; behavioral genetics; child (0-11); disease /disorder proneness /risk; dyslexia; family genetics; genetic markers; human genetic material tag; human subject; immunogenetics; language development; learning disorders; linkage mapping; magnetic resonance imaging; major histocompatibility complex; neuroanatomy; neuropsychological tests; psychological tests; quantitative trait loci; twin /multiplet

The overall goal of the proposed research is to achieve a clearer neuroscientific understanding of developmental dyslexia (or reading disability--RD) by means of an integrated program of research across four levels of analysis: 1) genetic, 2) neurological, 3) cognitive, and 4) behavioral. The specific aims and corresponding methodologies for each level of analysis are listed below. Genetic l) To test the hypothesis that there is a quantitative trait locus (QTL) in or near the human lymphocytic antigen (HLA) region of chromosome 6 which both influences RD and alters immune function. This hypothesis will be tested by means of convergent immune and linkage studies. 2) To confirm or disconfirm a linkage between RD and markers on the long arm of chromosome 15 and to screen for other loci on chromosomes besides 6 or 15 that influence RD. This will be accomplished by means of sibling pair linkage studies in two, differently ascertained samples. Neurological 3) To test for genetic and environmental influences on brain structure in RD by performing morphometric analyses of MRI scans collected from RD twin pairs in the Colorado Learning Disability Research Center (CLDRC). Cognitive 4) To test the hypothesis that deficits in phoneme segmentatian are a causal precursor to RD by means of a longitudinal study of young children at high and low family risk for RD. Behavioral 5) To examine the causal basis of the comarbidity between RD and ADHD (and other psychiatric disorders) by doing behavior genetic analyses of psychiatric rating scales and neuropsychological measures of executive function. The measures are being collected from the RD twin sample included in the CLDRC.

拟议研究的总体目标是实现更清晰的 对发育阅读障碍的神经科学理解（或阅读 残疾 - rd）通过集成的研究计划 在四个级别的分析中：1）遗传，2）神经系统，3） 认知和4）行为。具体目标和相应的目的 下面列出了每个分析级别的方法。 遗传 l）测试存在定量性状基因座的假设 （QTL）在或附近的人淋巴细胞抗原（HLA）区域 6染色体都会影响RD和改变免疫功能。 该假设将通过收敛免疫和 连锁研究。 2）确认或不确认RD与标记之间的联系 15号染色体的长臂，并在其他基因座上进行筛选 除6或15的染色体影响RD。这将是 通过兄弟姐妹成对链接研究完成的两个 确定样本的不同对样本。 神经系统 3）测试遗传和环境对大脑的影响 通过对MRI扫描进行形态计量分析，在RD中的结构 在科罗拉多学习障碍中从RD双胞胎对收集 研究中心（CLDRC）。 认知的 4）测试音素段落中缺陷的假设是 通过纵向研究的年轻人的因果前体 较高和低家庭风险的儿童。 行为 5）检查RD和RD之间的稳定性的因果关系 通过做行为遗传的ADHD（和其他精神疾病） 精神病量表和神经心理学的分析 执行功能的度量。这些措施正在收集 来自CLDRC中包含的RD双胞胎样本。