Genetic Dissection of Restricted Repetitive Behavior (RRB)

本K23应用程序的目的是培养科学发展和临床研究技能， 候选人。候选人在精神病学/儿童精神病学和研究方面接受过结构化的临床培训 与艾德库克博士一起接受培训，研究儿童期发病的精神疾病的分子遗传基础。的 候选人将通过独特的整合来自不同资源的专业知识来扩展她的研究技能 定制的职业发展计划。 研究计划的重点是调查限制性重复行为的遗传基础 （RRB）。RRB是描述各种异常重复行为的术语（例如，刻板、重复 自伤行为、强迫、强迫、仪式化行为、千篇一律的行为和 限制利益）。RRB是自闭症谱系障碍（ASD）的核心特征之一，也是自闭症的一个重要特征。 常见于Prader-Willi综合征（PWS）。RRB经常主导受影响患者的日常活动 个体，干扰发展功能行为的机会，需要干预， 治疗尽管RRB具有重要的功能意义，但其潜在的遗传机制却知之甚少。 在这个K23应用程序中，候选人建议检查染色体内的遗传变异 15 q11-q13区域，并测试遗传变异与RRB的特定形式之间的关联， 患有PWS的人和患有ASD的儿童。本项目的长期目标是了解 RRB的神经生物学机制跨临床类别。候选人的培训背景 临床精神病学和分子遗传学为这项工作提供了极好的基础。 职业发展计划旨在通过以下方式培养候选人的研究技能：（1） Mark刘易斯、Dan Drivel和艾德库克博士的指导，他们在RRB/动物模型方面具有专长， PWS/基因组印记和自闭症/分子遗传学;（2）评估的具体培训 自闭症、PWS和RRB的研究;（3）咨询统计遗传学和高通量SNP专家 基因分型;（4）包括研究设计，数据分析，流行病学， 和伦理;（5）出席科学会议并在会议上发言;（6）拟议的研究。给了她 之前的培训，建议的指导和优秀的资源，这个K23奖将允许候选人 成为神经发育遗传性疾病领域的独立临床研究者。 相关性（参见说明）： 我们的最终研究目标是在两个年龄段中确定限制性重复行为（RRB）的遗传因素。 临床实体：自闭症谱系障碍（ASD）和普拉德-威利综合征（PWS）。因此，积极 本研究的结果将为RRB的发病机制和新的治疗方法提供有价值的见解 在患有这些慢性和破坏性临床疾病的个体中。

The purpose of this K23 application is to foster scientific development and clinical investigational skills of the candidate. The candidate has had structured clinical training in psychiatry/child psychiatry and research training with Dr. Ed Cook studying molecular genetic bases of childhood-onset psychiatric disorders. The candidate will expand her research skills through a unique integration of expertise from diverse resources and customized career development plan. The research plan focuses on investigation of genetic underpinnings of restricted repetitive behavior (RRB). RRB is a term to describe a wide variety of abnormal repetitive behavior (e.g., stereotypy, repetitive forms of self-injurious behavior, obsession, compulsion, ritualistic behavior, sameness behavior and restricted interests). RRB is one of the core features of autism spectrum disorders (ASDs) and is also commonly observed in Prader-Willi syndrome (PWS). RRB frequently dominates daily activities of affected individuals, interferes with opportunities to develop functional behaviors, and requires intervention and treatment. Despite functional significance of RRB, little is known about underlying genetic mechanism. In this K23 application, the candidate proposes to examine genetic variations within the chromosome 15q11-q13 region and to test association between genetic variants and specific forms of RRB among individuals with PWS and children with ASD. The long-term goal of this project is to understand the common neurobiological mechanism for RRB across the clinical categories. The candidate's training background in clinical psychiatry and molecular genetics provides an excellent foundation for this work. The Career Development Plan is designed for the candidate to develop her research skills by (1) the mentorship of Drs. Mark Lewis, Dan Driscoll, and Ed Cook, who have expertise in RRB/animal models, PWS/genomic imprinting, and autism/molecular genetics, respectively; (2) specific training in assessments of autism, PWS, and RRB; (3) consultation with experts in statistical genetics and high-throughput SNP genotyping; (4) formal didactic training in disciplines including study design, data analysis, epidemiology, and ethics; (5) attendance and presentation in scientific meetings, and (6) the proposed study. Given her prior training, proposed mentorship, and outstanding resources, this K23 Award will permit the candidate to become an independent clinical investigator in the field of neurodevelopmental genetic disorders. RELEVANCE (See instructions): Our ultimate research aim is to identify genetic factors for restricted repetitive behavior (RRB) across two clinical entities: autism spectrum disorders (ASDs) and Prader-Willi syndrome (PWS). Therefore, positive results from this study should provide valuable insights into pathogenesis and novel treatment of RRB among individuals with these chronic and devastating clinical conditions.