Genetic investigation of cognitive development in autistic spectrum disorders.

描述（由申请人提供）：本申请申请K23职业发展奖，题目为“自闭症谱系障碍认知发展的基因研究”。候选人有医学博士和博士学位。他的博士研究方向是遗传小鼠模型的分子神经发育。他在麻省理工学院接受本科培训，并在哈佛医学院的哈佛-麻省理工学院健康科学与技术部门获得博士学位，涉及定量方法的研究。候选人在MGH- McLean精神病学住院医师中心接受了临床培训。他是哈佛医学院精神病学讲师，在MGH和波士顿儿童医院任职，同时也是麻省理工学院和哈佛大学Broad研究所的博士后。如果成功，申请人的职业轨迹是在MGH领导一个以分子精神病学为基础的实验室项目，重点是自闭症和相关的认知发展障碍。与这个转化研究实验室相联系，候选人计划指导MGH精神病学中患有广泛性发育障碍的成人临床研究项目。候选人的研究计划描述了旨在识别自闭症谱系障碍（ASD）基因的研究。候选人建议研究两个互补的患者群体：1)来自阿拉伯中东，土耳其和巴基斯坦的特殊创始人群，其中受影响儿童的父母是近亲；2)来自AGRE和波士顿自闭症协会的大量北美家庭（约4000个样本），包括候选人建议在MGH儿科精神病学中描述的200个家庭的队列。近亲谱系将作为自闭症国际纯合子图谱合作组织（候选人担任副主任）的一部分被登记，目的是发现高渗透的常染色体隐性基因。分析的主要工具将是Affymetrix 500K SNP微阵列，研究将包括基因组拷贝数，以及缺失和纯合子图谱。由此确定的基因将在北美患者中使用大规模重测序、关联研究和表型-基因型研究进行研究。导师包括克里斯A.沃尔什，医学博士，波士顿儿童医院遗传学主席和波士顿自闭症协会主任。沃尔什博士的实验室在国际基因合作和识别神经发育和认知障碍中的隐性基因方面具有专长。此外，布罗德研究所的统计遗传学家马克·j·戴利博士将担任共同导师。该候选人正在寻求人口学、统计遗传学和生物信息学方面的培训。他也在寻求以患者为导向的自闭症研究培训，这将通过儿童医院的发展医学中心以及国家尊重的外部自闭症研究专家来进行。

DESCRIPTION (provided by applicant): This application for a K23 Career Development Award is entitled "Genetic investigation of cognitive development in autistic spectrum disorders". The candidate has MD and PhD degrees. His PhD is in molecular neurodevelopment in genetic mouse models. His undergraduate training at MIT, and his MD in the Harvard-MIT Division of Health Sciences and Technology at Harvard Medical School involved studies in quantitative methods. The candidate has pursued clinical training through to Chief Residency in the MGH- McLean Psychiatry Residency. He is an Instructor in Psychiatry at Harvard Medical School with appointments at the MGH and Children's Hospital Boston, as well as a postdoctoral affiliation with the Broad Institute of MIT and Harvard. If successful, the career trajectory for this applicant is to lead a laboratory- based program in Molecular Psychiatry at MGH with a focus in autism and related disorders of cognitive development. Linked to this translational research lab, the candidate plans to direct a Clinical Research Program for Adults with Pervasive Development Disorders in MGH Psychiatry. The candidate's research proposal describes studies designed to identify genes in autism spectrum disorders (ASD). The candidate proposes to study two complementary patient populations: 1) a special founder population from the Arabic Middle East, Turkey and Pakistan, wherein parents of affected children are consanguineous; and 2) a large collection of North American families (>4000 samples) from AGRE and the Boston Autism Consortium, including a cohort of 200 families which the candidate proposes to characterized in MGH Pediatric Psychiatry. The consanguineous pedigrees will be enrolled as part of the Autism International Homozygosity Mapping Collaborative (for which the candidate serves as Associate Director) with the aim of discovering highly penetrant autosomal recessive genes. A principal tool for analysis will be the Affymetrix 500K SNP microarray, and studies will include genomic copy number, as well as deletion and homozygosity mapping. Genes thereby identified will be studied in the North American patients using large-scale resequencing, association studies and phenotype-genotype studies. Mentors include Chris A. Walsh, MD, PhD, Chair of Genetics at the Children's Hospital Boston and Director of the Boston Autism Consortium. Dr. Walsh's lab has expertise in international genetic collaborations and identifying recessive genes in neurodevelopmental and cognitive disorders. In addition, Mark J. Daly, PhD, a statistical geneticist at the Broad Institute will serve as co-mentor. The candidate is seeking training in human population and statistical genetics, and bioinformatics. He is also seeking patient- oriented research training in ASD which will be pursued through the Developmental Medicine Center at Children's Hospital, as well as with external autism research experts of national esteem.