Molecular genetics of executive function in dyslexia

阅读障碍执行功能的分子遗传学

• 批准号: 7005434
• 负责人: Zoran Brkanac
• 金额: $ 17.21万
• 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/7005434
• 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)：这项培训资助的目的是帮助候选人在精神病学和行为遗传学领域建立独立的研究生涯。应聘者已完成精神病学和儿童精神病学的临床培训，并具有简单孟德尔和基因组疾病的分子遗传学研究经验。候选人的培训将在华盛顿大学温迪·拉斯金德博士的实验室进行。拉斯金德博士是一个研究诵读困难的多学科研究团队的成员。本研究旨在探讨阅读障碍的遗传学基础。阅读困难症是一种常见而复杂的疾病，遗传学在其中有重要的作用。语音加工受损和潜在的语言加工被认为是阅读障碍的核心缺陷。近年来，注意力和执行功能因素的作用日益得到认可。注意力和执行功能缺陷通常出现在许多遗传性精神障碍中。阅读障碍还表现出与儿童精神障碍(如ADHD)显著的共病。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障碍的遗传基础。尽管阅读障碍的遗传学研究由于缺乏诊断标准的共识和遗传异质性而变得复杂，但这项研究将使用复杂的表型评估和统计分析方法来克服这些并发症，并识别与这种复杂的行为表型有关的基因。为了阐明阅读障碍的遗传基础，申请人建议： (1)评价注意力和执行功能成分表型对遗传学研究的适用性。 (2)通过全基因组的连锁分析，定位影响注意力和执行功能的量化指标的基因。 (3)评估与注意网络有关的候选基因与已识别的阅读障碍的组成表型之间的关系 (4)提炼特定目标确定的遗传基因座(2) 应聘者的直接职业目标是获得研究复杂遗传疾病的必要技能。这笔培训补助金将使应聘者能够以他以前在“简单”孟德尔疾病分子遗传学方面的经验为基础，并为申请者提供机会(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的分子遗传学技能，(3)获得与复杂遗传学研究相关的新的统计遗传学技能。这些目标将通过正式的教学课程和实验室、联系和联合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学。