A Family-Genetic Study of Autism and Fragile X Syndrome

 描述（由申请人提供）：本修订申请的父代R 01旨在通过研究遗传易感性增加的一级亲属（自闭症患者的亲属和FXS患者的亲属，即FMR 1前突变携带者），了解FMR 1相关分子变异在自闭症遗传学中的作用。该提案建立在我们先前对自闭症和广泛自闭症表型（BAP）的研究基础上，以检查与自闭症和BAP共分离的关键发育，临床，语言和社会认知表型。我们正在研究这些表型的前突变携带者相比，从一级亲属收集的数据与自闭症患者，以确定潜在的重叠的配置文件跨组，这可能与FMR 1相关的分子变异。最初的提案还利用了一个前所未有的机会--从一个国家获得档案儿童语言和认知测试记录。 FXS和自闭症患者的大家族队列。该项目进展强劲而稳定，同时，一项旨在识别自闭症和BAP中具有遗传意义的语言特征的伴随基金也产生了一些重要的发现。我们在生产中试用了这些措施，并可能与自主觉醒有关。与一个扩大的专家合作者小组的前突变携带者，与令人兴奋的结果。在这个修订版的应用程序中，我们提出了一个电池的工具，用于分析话语生产，利用心理语言学和计算语言学已经开发的技术，初步数据表明，可能会捕捉重要的语言相关的配置文件中的BAP和FMR 1前突变。这些工具提供了话语的关键词汇和语义特征的定量测量，以及使用眼动追踪提供关于语言处理如何与话语过程中的感知和注意力联系在一起的新信息，我们相信，增加这些新的语言测量将大大提高我们现有数据的价值，并加深我们对FMR 1作用的理解，更具体地说，FMRP，在孤独症诊断学中，以及进一步表征FMR 1前突变的表型。

 DESCRIPTION (provided by applicant): The parent R01 for this revision application was intended to inform the role of FMR1-related molecular variation in autism symptomatology through the study of 1st degree relatives who are at increased genetic liability - relatives of individuals with autism and relatives of individuals with FXS, who are carriers of the FMR1 premutation. The proposal built on our prior studies of autism and the broad autism phenotype (BAP), to examine key developmental, clinical, language, and social cognitive phenotypes shown to cosegregate with autism and the BAP. We are examining these phenotypes among premutation carriers in comparison to data collected from 1st degree relatives of individuals with autism, to identify potentially overlapping profiles across groups, which may be linked to FMR1-related molecular variation. The original proposal also capitalized on an unprecedented opportunity -- the availability of archival childhood language and cognitive testing records from a large cohort of families of individuals with FXS and autism. The project has proceeded strongly and steadily, while at the same time a number of important findings have emerged from a companion grant focused on identifying genetically meaningful language features in autism and the BAP. We piloted these measures in a production, and potentially related to autonomic arousal. With an expanded team of expert collaborators subgroup of premutation carriers, with exciting results. In this revision application we propose a battery of tools for analyzing discours production, drawing on techniques that have been developed in psycholinguistics and computational linguistics, and which Preliminary Data suggest may capture important language-related profiles in the BAP and the FMR1 premutation. These tools provide quantitative measures of key lexical and semantic features of discourse, as well as using eye tracking to provide new information on how language processing is linked to perception and attention during discourse included, we believe that the addition of these novel measures of language will substantially enhance the value of our existing data, and sharpen our understanding of the role of FMR1, and FMRP more specifically, in autism symptomatology, as well as further characterize the phenotype of the FMR1 premutation.