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转变为一名独立的临床医生和科学家，致力于研究神经发育不良结果的遗传易感性。2009年6月，我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，我一直是尤尼斯·肯尼迪·施莱弗NICHD母胎医学单位网络指导专业临床研究人员发展奖(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年的奖项符合K-Funding的资格，将于2009年8月结束。我正在完成我为MSCIDA奖资助的所有培训和研究目标。这项研究在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。这份建议概述了一个延长的培训和研究计划，将为我提供总共5年的受保护的指导时间，并将导致我实现成为一名独立的、外部资助的和自给自足的临床医生兼科学家的目标。我的具体职业发展目标是1)扩展研究设计、分析和结果解释的现有技能，2)发展获得、管理和分析基因数据的额外技能，3)发展临床试验设计和实施的额外技能，4)发展领导多学科研究团队的技能，5)了解临床遗传学和神经发育障碍研究的伦理和法律影响。我的具体研究目标是：1)使用定制的多重SNP分析来确定与早产儿CP相关的基因多态性，该方法旨在评估炎症、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分析来确定与早产儿神经发育延迟相关的基因多态性；以及3)进行分析，以确定导致神经发育不良结局易感性的独特的基因-基因和基因-环境相互作用。这一建议代表了一个独特的机会，在一个大的队列中，将遗传多态与具有良好特征的神经发育结果相关联。这也是获得多学科培训和研究经验的独特机会，以支持我的职业目标，即成为全国公认的胎儿遗传因素专家，这些因素会导致不利的神经发育结果。 公共卫生相关性：尽管各种围产期并发症会增加个体发生脑瘫或其他形式的神经发育迟缓的风险，但高危个体发生这些并发症的机制尚不完全清楚。这项工作将有助于加深对导致早产儿脑损伤的遗传风险因素的了解，因此将确定可能的预防策略，并可能为未来的预防/干预试验提供基础。它还将促进一个有前途的年轻临床医生-科学家的职业发展，在一个被证明有职业发展能力的环境中。克拉克博士得到了她所在部门、部门和机构的热情支持(包括至少75%的保护时间和适当的机构资金)。

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).