Genomic Analyses

基因组分析

基本信息

批准号：
10251951
负责人：
JEFFREY R GRUEN
金额：
$ 24.44万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251951
关键词：
Affect Age Architecture Attention Attention deficit hyperactivity disorder Behavioral Biological Brain Characteristics Child Clinical Cognitive Collection Colorado Complex Cross-Sectional Studies Data Development Diagnosis Differential Diagnosis Environment Environmental Risk Factor Ethnic Origin Family Fostering Frequencies Funding Genes Genetic Genetic Markers Genetic study Genomics Goals Growth Heritability Image Individual Individual Differences Instruction Intervention Intervention Trial Knowledge Language Learning Learning Disabilities Longitudinal Studies Mathematics Measures Methods Molecular Neural Pathways Neurobiology Neurocognitive Neuropsychological Tests Neuropsychology Other Genetics Pathway interactions Performance Phenotype Population Heterogeneity Prospective cohort Race Reading Reading Disabilities Research Research Design Research Personnel Sampling Schools Siblings Socioeconomic Status Testing Variant base brain circuitry causal variant comorbidity conditioning disability risk endophenotype ethnic diversity ethnic minority population executive function gene environment interaction genetic variant genome wide association study genome-wide holistic approach imaging genetics improved mathematics disability neural network neuroimaging phonology pleiotropism processing speed racial minority rare variant relating to nervous system remediation sex skills targeted sequencing trait transmission process treatment response

项目摘要

PROJECT SUMMARY/ABSTRACT PROJECT IV: GENOMIC ANALYSES The overall theme of the Colorado Learning Disabilities Research Center (CLDRC) is that multiple different learning disabilities – including reading disability, math disability, and attention deficit hyperactivity disorder – frequently occur in the same individual as a result of deficits that affect multiple underlying functional domains. Some of these deficits affect a single domain such as phonological processing, and some affect multiple domains such as phonological processing and attention and processing speed. In the projects within the CLDRC, these functional domains will be characterized by their genetic and developmental characteristics and by their interactions with an individual’s environment. In Project IV, we focus on the genetic characteristics of these functional domains at the molecular level through several approaches. We hypothesize that some genetic variants specifically affect a single domain while other genetic variants affect multiple domains. To identify these genetic variants, we will continue our studies of CLDRC families through targeted sequencing in chromosomal regions in which we find genetic effects in a specific domain, and we will extend our search for genetic variants that have effects on multiple domains. We will modify methods for generating a learning disability risk score, based on genome-wide variation, that could be clinically useful and widely applicable regardless of race, ethnicity or sex. We will also examine individual and shared brain circuits that are critical for learning. We will identify the genes that help to determine how well these circuits are formed and function, and will relate these circuits and genes to the functional domains that they serve. Finally, in partnership with an on- going intervention trial for reading disability called the New Haven Lexinome Project, we will examine the genetic basis for differential rates of acquisition of reading skill, the influence of attention, and the interactions between the genetic and the environmental (instruction) effects in an ethnically diverse population of public school children. The overall goal of Project IV is to disentangle the individual and shared genetic, neurobiological, and environmental factors that underlie learning disabilities, and to foster development of useful strategies for diagnosis, for informing effective remediation and for developing interventions.

项目概要/摘要项目四：基因组分析科罗拉多学习障碍研究中心 (CLDRC) 的总体主题是，多种不同的学习障碍——包括阅读障碍、数学障碍和注意力缺陷多动障碍—— 由于影响潜在多个功能域的缺陷，这些缺陷经常发生在同一个人身上。其中一些缺陷影响单个领域，例如语音处理，有些影响多个领域语音处理、注意力和处理速度等领域。 CLDRC，这些功能域将以其遗传和发育特征为特征，在项目 IV 中，我们重点关注个体的遗传特征。这些功能域在分子水平上通过多种方法实现。遗传变异专门影响单个域，而其他遗传变异则影响多个域。确定这些遗传变异后，我们将通过靶向测序继续对 CLDRC 家族进行研究我们在特定领域发现遗传效应的染色体区域，我们将扩大我们的搜索范围我们将修改生成学习的方法。基于全基因组变异的残疾风险评分，可能在临床上有用且广泛适用无论种族、民族或性别如何，我们还将检查对人类至关重要的个人和共享的大脑回路。我们将识别有助于确定这些回路的形成和功能的基因，以及最后，将把这些电路和基因与它们所服务的功能域联系起来。阅读障碍的干预试验称为纽黑文 Lexinome 项目，我们将检查阅读技能获得率差异的遗传基础、注意力的影响以及相互作用在不同种族的公众群体中，遗传和环境（指导）效应之间的关系项目 IV 的总体目标是解开个体和共享遗传的束缚，造成学习障碍的神经生物学和环境因素，并促进发展有用的诊断策略、为有效补救提供信息以及制定干预措施。