Early Genomic Diagnosis

摘要 我在2010年完成了产妇胎儿医学和临床遗传学的奖学金培训。从那时起，遗传学的科学已经发展，我现在需要进一步的基因组学和生物信息学的培训，以完成我的研究目标，并跟上临床遗传学发生的变化。完成K23将为我提供分子基因组技术，分子变异分析，生物信息学，统计遗传学方面的进一步教育，并使我能够增加对在临床实践中实施基因组技术的伦理，法律的和社会影响的理解。这些技能对我实现我的长期目标是必要的，即使用创新工具来确定影响新生儿和母亲的遗传疾病的根本原因，并将这些发现转化为改进的临床实践。获得K23是我职业发展的下一个合乎逻辑的步骤，因为它将为我提供必要的教学培训和实践指导研究经验，为未来的独立NIH奖项生成试点数据。 全外显子组测序（WES）是一种创新的基因组技术，已被证明是成人和儿童的强大诊断工具，但尚未在早期阶段进行研究。为了评估这种变革性技术的使用，我将在怀疑有标准基因检测未确定的遗传病因的妊娠中应用WES。我会对52个这样的黑社会进行ES测试。目标1的目的是确定怀疑有遗传病因的孕妇中的主要遗传异常，而标准遗传检测未确定遗传病因。通过完成目标1，我们将能够评估WES在产前人群中的性能，并确定可以指导其应用的关键临床特征。目标2将衡量遗传信息对父母的影响。这些信息将被用来制定一个伦理框架，将WES引入产科环境和一套考虑因素，包括在决策辅助工具，咨询协议，并在未来的研究中使用的早期外显子组测序的定量调查。这项提案的结果是朝着我的长期目标迈出的第一步，即建立一套最佳实践，以指导未来实施新的和创新的基因组技术，使家庭受益。

ABSTRACT I completed Fellowship Training in Maternal Fetal Medicine and Clinical Genetics in 2010. Since then, the science of genetics has evolved such that I now require further training in genomics and bioinformatics to complete my research goals and to keep pace with the changes occurring in clinical genetics. Completion of the K23 would provide me with further education in molecular genomic techniques, molecular variant analysis, bioinformatics, statistical genetics, and allow me to increase my understanding of the ethical, legal, and social implications of implementing genomic technologies in clinical practice. These skills are necessary for me to achieve my long term goal to use innovative tools to identify the root causes of genetic disorders that affect newborns and mothers and to translate these findings into improved clinical practice. Obtaining the K23 is the next logical step in my career development, because it will provide me with the essential didactic training and hands-on mentored research experience to generate pilot data for a future independent NIH award. Whole exome sequencing (WES) is an innovative genomic technology that has proven to be a powerful diagnostic tool in adults and children but has not been studied at earlier stages. To evaluate the use of this transformative technology, I will apply WES in pregnancies suspected to have a genetic etiology not identified by standard genetic testing. I will perform ES testing on 52 such triads. The goal of aim 1 is to identify major genetic abnormalities in pregnancies suspected to have a genetic etiology not identified by standard genetic testing. By completing Aim 1, we will be able to evaluate the performance of WES in a prenatal population, and identify critical clinical characteristics that can guide its application. Aim 2 will measure the impact of genetic information on parents. This information will be used to develop an ethical framework for the introduction of WES into the obstetric setting and a set of considerations to include in decision aids, counseling protocols, and quantitative surveys for use in future studies of early exome sequencing. The results from this proposal are the first step toward my long term goal to establish a set of best practices to guide future implementation of new and innovative genomic technologies to benefit families.