Genetic Polymorphisms Associated with Cerebral Palsy and Neurodevelopmental Delay

描述（由申请人提供）：这个职业发展奖旨在支持我过渡到一个独立的临床医生-科学家，致力于研究不良神经发育结果的遗传易感性。我于2009年6月在犹他大学健康科学中心完成了母胎医学奖学金。从2007年7月至今，我一直是Eunice Kennedy Shriver NICHD母胎医学单位网络的指导专业临床研究者发展奖（MSCIDA）的获得者，该奖项为初步培训和研究提供了支持。这项为期2年的奖励符合k基金的资格，将于2009年8月结束。我正在完成我为获得MSCIDA奖而资助的所有培训和研究目标。本研究在2009年母胎医学学会会议（口头）和2009年妇科调查学会会议（口头）上发表。这份提案概述了一个扩展的培训和研究计划，它将为我提供总共5年的受保护和指导的时间，并将导致我成为一名独立的，外部资助和自我维持的临床科学家的目标。我的具体职业发展目标是：1)扩展研究设计、分析和结果解释方面的现有技能；2)在遗传数据的获取、管理和分析方面培养额外的技能；3)在临床试验的设计和实施方面培养额外的技能；4)培养多学科研究团队的领导技能；5)理解临床遗传学和神经发育障碍研究的伦理和法律含义。我的具体研究目标是：1)使用一种定制的多重SNP检测方法识别与早产儿CP相关的遗传多态性，该方法设计用于评估炎症、凝血、血管调节和其他基因中的约1300个SNP； 2)使用相同的定制多重SNP检测方法识别与早产儿神经发育迟缓相关的遗传多态性。3)进行分析，以确定独特的基因-基因和基因-环境相互作用，有助于易感性的不良神经发育结果。这一建议代表了一个独特的机会，在一个大的队列中，遗传多态性与特征明确的神经发育结果的相关性。这也是一个获得多学科培训和研究经验的独特机会，以支持我成为全国公认的胎儿遗传因素专家的职业目标，这些因素有助于不良的神经发育结果。

DESCRIPTION (provided by applicant): This career development award is designed to support my transition into an independent clinician-scientist dedicated to the study of genetic susceptibility to adverse neurodevelopmental outcomes. I completed a Maternal Fetal Medicine Fellowship at the University of Utah Health Sciences Center in June 2009. From July 2007 to present, I have been the recipient of the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network's Mentored Specialized Clinical Investigator Development Award (MSCIDA), which has provided support for initial training and research. This 2-year award qualifies as K-funding and will end in August 2009. I am fulfilling all of my funded training and research goals for the MSCIDA award. This research was presented at the 2009 Society of Maternal Fetal Medicine meeting (oral) and the 2009 Society for Gynecologic Investigation meeting (oral). This proposal outlines an extended training and research program that will provide me with a total of 5 years of protected, mentored time and will result in achievement of my goal of becoming an independent, extramurally funded and self-sustaining clinician-scientist. My specific career development aims are to 1) expand existing skills in study design, analysis, and interpretation of results, 2) develop additional skills in the acquisition, management, and analysis of genetic data, 3) develop additional skills in the design and implementation of clinical trials, 4) develop skills for leadership of a multi-disciplinary research team, and 5) understand the ethical and legal implications of research in clinical genetics and neurodevelopmental disability. My specific research aims are to 1) identify genetic polymorphisms that are associated with CP in preterm infants using a custom, multiplex SNP assay designed to assess ~1300 SNPs in inflammation, coagulation, vascular regulation and other genes, 2) identify genetic polymorphisms that are associated with neurodevelopmental delay in preterm infants using the same custom multiplex SNP assay, and 3) perform analyses to identify unique gene-gene and gene-environment interactions that contribute to susceptibility to adverse neurodevelopmental outcomes. This proposal represents a unique opportunity for correlation of genetic polymorphisms with well- characterized neurodevelopmental outcomes in a large cohort. It is also a unique opportunity to gain multi- disciplinary training and research experience to support my career goal of becoming a nationally-recognized expert in fetal genetic factors that contribute to adverse neurodevelopmental outcomes. PUBLIC HEALTH RELEVANCE: Although various perinatal complications increase the risk of an individual developing cerebral palsy or other forms of neurodevelopmental delay, the mechanisms by which at-risk individuals develop these complications are incompletely understood. This work will contribute to an increased understanding of the genetic risk factors predisposing a premature fetus to brain injury, and will therefore identify possible prevention strategies and may provide a basis for future prevention/ intervention trials. It will also enhance the career development of a promising young clinician-scientist within an environment with proven career-development capabilities. Dr. Clark has the enthusiastic support of her Division, Department and Institution (including at least 75% protected time and appropriate institutional funding).