Center for Genomic and Phenomic Studies in Autism

描述（由申请人提供）：本申请要求五年的支持，以建立一个自闭症基因组和表型研究中心，涉及南加州大学（USC）、自闭症遗传资源交换中心（AGRE）、MIND研究所/加州大学（UC）-戴维斯分校、密歇根大学、洛杉矶儿童医院（CHLA）和E.K. Shriver中心/马萨诸塞州大学医学院。该中心汇集了一个杰出的多学科研究人员团队，他们在多元谱系中的自闭症基因组学和表型学方面具有相当的专业知识，包括全国范围内的家庭确认和筛查，高通量诊断，最先进的临床评估和结构访谈，认知和行为评估，3D颅面形态学，细胞遗传学，DMA微阵列，免疫学，结构脑成像，电生理学，环境风险评估。我们的研究团队在协调和向科学界广泛传播自闭症的表型和基因组信息方面也有相当丰富的经验。我们已经确定了超过1,400个有两个或更多受影响儿童的谱系，目前通过AGRE和NIMH人类遗传学倡议分发了全面的临床数据，DMA和细胞系。该中心将利用全国性的确认策略，并从1，500个多重自闭症谱系的新种族多样性样本中收集最先进的高通量表型信息和血液，这些样本将与国家自闭症研究数据库（NDAR）和NIMH人类遗传学倡议共享。对受影响儿童进行的高通量表型组学将包括最先进的临床仪器和结构访谈，以评估行为，社会，认知/智力，语言/沟通和适应功能。还将进行细胞遗传学和基线环境风险评估。将在加州的625名自闭症儿童的子集中进行试点研究，以使用最先进的3D颅面形态学、结构脑成像、DNA微阵列、免疫测定、听觉诱发电位和其他心理生理学测量以及空气质量评估技术来识别稳健的内表型。我们的提案的独特优势包括：（1）包括AGRE和MIND研究所/UC-Davis的既定项目，这些项目将利用现有的基础设施，包括USC/CHLA的一般临床研究中心;（2）AGRE在建立全国范围的自闭症研究表型和基因组资源收集方面的丰富经验;以及（3）高效生物信息学算法和基于网络的数据管理系统的可用性。我们中心的最终目标是促进自闭症的遗传和环境研究，从而提高诊断水平，加速我们对其病因学和病理生理学的理解，并促进新疗法的发现。

DESCRIPTION (provided by applicant): This application requests five years of support to establish a Center for Genomic and Phenomic Studies in Autism involving the University of Southern California (USC), Autism Genetic Resource Exchange (AGRE), MIND Institute/University of California (UC) - Davis, University of Michigan, Children's Hospital Los Angeles (CHLA), and E.K. Shriver Center/University of Massachusetts Medical School. The Center brings together a distinguished multidisciplinary team of investigators with considerable expertise in the genomics and phenomics of autism in multiplex pedigrees, including nationwide family ascertainment and screening, high throughput diagnostics, state-of-the-art clinical evaluation and structural interviewing, cognitive and behavioral evaluations, 3D craniofacial morphology, cytogenetics, DMA microarrays, immunology, structural brain imaging, electrophysiology, and environmental risk assessment. Our research team also has considerable experience in coordinating and widely distributing to the scientific community phenomic and genomic information in autism. We have identified over 1,400 pedigrees with two or more affected children, for which comprehensive clinical data, DMA and cell lines are currently distributed through AGRE and the NIMH Human Genetics Initiative. The Center will utilize a nationwide ascertainment strategy with a demonstrated record of success and collect state-of-the-art high-throughput phenotypic information and blood from a new ethnically diverse sample of 1,500 multiplex autism pedigrees that will be shared with the National Database for Autism Research (NDAR) and the NIMH Human Genetics Initiative. High-throughput phenomics conducted on affected children will include state-of-the-art clinical instrumentation and structural interviews to assess behavioral, social, cognitive/intellectual, language/communicative and adaptive functioning. Cytogenetic and baseline environmental risk assessments also will be made. Pilot studies in a subset of 625 autistic children in California will be conducted to identify robust endophenotypes using state of- the-art technologies for 3D craniofacial morphology, structural brain imaging, DNA microarrays, immunological assays, auditory evoked potentials and other psychophysiological measures, and air quality assessments. Unique strengths of our proposal include: (1) the inclusion of established programs at AGRE and the MIND Institute/UC - Davis that will utilize pre-existing infrastructure, including USC/CHLA's General Clinical Research Center; (2) AGRE's considerable experience in establishing a nationwide collection of phenomic and genomic resources for autism research; and (3) the availability of highly efficient bioinformatics algorithms and a web-based data management system. The ultimate goal of our Center will be to facilitate genetic and environmental studies on autism, thereby improving diagnosis, accelerating our understanding of its etiology and pathophysiology, and facilitating discovery of new therapeutics.