Molecular genetics of executive function in dyslexia

阅读障碍执行功能的分子遗传学

• 批准号: 6857565
• 负责人: Zoran Brkanac
• 金额: $ 16.91万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6857565
• 关键词: attention; attention deficit disorder; behavioral /social science research tag; behavioral genetics; clinical research; data collection methodology /evaluation; disease /disorder etiology; dyslexia; family genetics; functional ability; genetic disorder; genetic polymorphism; human subject; middle childhood (6-11); molecular genetics; phenotype; phonology; psychiatry; quantitative trait loci; statistics /biometry; training

Description (provided by the applicant): The purpose of this training grant is to help establish the candidate's independent research career in the field of psychiatric and behavioral genetics. The candidate has completed clinical training in psychiatry and child psychiatry, and has prior research experience in molecular genetics of simple Mendelian and genomic disorders. The candidate's training will take place in the laboratory of Dr. Wendy Raskind at the University of Washington. Dr. Raskind is part of an established multidisciplinary research team investigating dyslexia. This study proposes to investigate the genetic basis for dyslexia. Dyslexia is a common and complex disorder in which genetics has a significant component. Impaired phonological processing and underlying language processes have been identified as core deficits in dyslexia. Recently, the contributions of attention and executive functioning factors have been increasingly recognized. Attention and executive function deficits are commonly observed in many heritable psychiatric disorders. Dyslexia also demonstrates significant comorbidity with psychiatric disorders of childhood such as ADHD. Studying the genetic basis of attention and executive functioning may help elucidate the genetic underpinnings of additional psychiatric disorders. Although genetic studies of dyslexia can be complicated by a lack of consensus on diagnostic criteria and by genetic heterogeneity, this study will employ sophisticated phenotype assessment and statistical analysis methodologies to overcome these complications and in order to identify genes that contribute to this complex behavioral phenotype. To elucidate the genetic basis of dyslexia, the applicant proposes to: (1) To evaluate attention and executive function component phenotypes for suitability for genetic studies. (2) To localize genes that contribute to performance on quantitative measures of attention and executive function by genome-wide linkage analyses (3) To evaluate candidate genes which are implicated in attention networks for association with the identified component phenotypes of dyslexia (4) To refine the genetic loci identified in Specific Aim (2) The candidate's immediate career goal is to acquire the necessary skills to study complex genetic disorders. This training grant will allow the candidate to build upon his prior experiences in the molecular genetics of "simple" Mendelian disorders and afford the applicant the opportunities to (1) learn methods for understanding and dissecting complex cognitive/behavioral phenotypes, (2) acquire new molecular genetics skills pertinent to common genetic variations and complex phenotypes, and (3) attain new statistical genetics skills relevant to the study of complex genetics. These goals will be accomplished through formal didactic coursework and practical performance of laboratory, linkage and association studies. The candidate's longterm career goal is to study the etiology of complex psychiatric disorders that have varying degrees of genetic influences.

描述（由申请人提供）：该培训补助金的目的是帮助建立候选人在精神病学和行为遗传学领域的独立研究生涯。候选人已经完成了精神病学和儿童精神病学的临床培训，并在简单孟德尔和基因组疾病的分子遗传学方面有过研究经验。候选人的培训将在华盛顿大学Wendy Raskind博士的实验室进行。Raskind博士是一个研究诵读困难的多学科研究小组的一员。本研究旨在探讨阅读障碍的遗传基础。阅读障碍是一种常见而复杂的疾病，其中遗传学具有重要的组成部分。受损的语音处理和潜在的语言过程已被确定为核心缺陷的阅读障碍。近年来，注意和执行功能因素的作用越来越受到重视。注意力和执行功能缺陷通常在许多遗传性精神疾病中观察到。阅读障碍也表现出与儿童精神疾病如ADHD的显著共病性。研究注意力和执行功能的遗传基础可能有助于阐明其他精神疾病的遗传基础。虽然阅读障碍的遗传学研究可以复杂的缺乏共识的诊断标准和遗传异质性，本研究将采用先进的表型评估和统计分析方法，以克服这些并发症，以确定基因，有助于这种复杂的行为表型。为了阐明阅读障碍的遗传基础，申请人建议： (1)评估注意力和执行功能组分表型是否适合遗传研究。 (2)通过全基因组连锁分析定位有助于注意力和执行功能定量测量的基因 (3)评估候选基因，这些基因与注意网络有关，与已确定的阅读障碍的组成表型有关 (4)完善特定目标（2）中确定的遗传位点 候选人的直接职业目标是获得研究复杂遗传疾病的必要技能。该培训补助金将允许候选人建立在他先前在“简单”孟德尔疾病的分子遗传学方面的经验基础上，并为申请人提供以下机会：（1）学习理解和剖析复杂认知/行为表型的方法，（2）获得与常见遗传变异和复杂表型相关的新分子遗传学技能，获得与复杂遗传学研究相关的统计遗传学新技能。这些目标将通过正式的教学课程和实验室，联系和协会研究的实际表现来实现。候选人的长期职业目标是研究具有不同程度遗传影响的复杂精神疾病的病因。