Early Genomic Diagnosis

早期基因组诊断

• 批准号: 9307014
• 负责人: Neeta L Vora
• 金额: $ 17.11万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-07 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307014
• 关键词: Address; Adult; Affect; Amniocentesis; Archives; Award; Bioinformatics; Blood; Case Study; Cell Extracts; Characteristics; Child; Chorion; Chorionic villi; Clinic; Clinical; Code; Counseling; Data; Decision Aid; Detection; Diagnosis; Diagnostic; Diagnostic tests; Discipline of obstetrics; Education; Embryo; Embryonic Development; Ethics; Exons; Family; Fellowship; Fertilization in Vitro; Fetal Death; Fetal Tissues; Fetus; Foundations; Fright; Future; Genes; Genetic; Genetic Predisposition to Disease; Genetic screening method; Genome; Genomics; Goals; Hereditary Disease; Human; Infant; Karyotype; Knowledge; Measures; Medical Genetics; Mentors; Methods; Modeling; Molecular; Molecular Abnormality; Mothers; Newborn Infant; Nucleotides; Parents; Performance; Plant Roots; Plasma; Population; Pregnancy; Prenatal Diagnosis; Process; Proteins; Protocols documentation; Publishing; Recurrence; Research; Risk; Sampling; Science of genetics; Sensitivity and Specificity; Specimen; Structural defect; Surveys; Techniques; Technology; Testing; Time; Training; Translating; Triad Acrylic Resin; Trisomy; Umbilical Cord Blood; Uncertainty; United States National Institutes of Health; Variant; Villus; Woman; base; career development; cell free fetal DNA; clinical care; clinical practice; congenital anomaly; exome sequencing; experience; fetal; fetal diagnosis; fetal medicine; gene discovery; genetic disorder diagnosis; genetic information; genome sequencing; improved; innovation; legal implication; negative affect; novel; preimplantation; prenatal; prospective; response; screening; skills; social implication; tool; whole genome

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.

抽象的 我于 2010 年完成了母胎医学和临床遗传学进修培训。从那时起，遗传学科学不断发展，我现在需要进一步接受基因组学和生物信息学培训，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，并使我能够加深对在临床实践中实施基因组技术的伦理、法律和社会影响的理解。这些技能对于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性疾病的根本原因，并将这些发现转化为改进的临床实践。获得 K23 是我职业发展中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，以便为未来的独立 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，我将在怀疑具有标准基因测试未识别的遗传病因的妊娠中应用 WES。我将对 52 个这样的三元组进行 ES 测试。目标 1 的目标是识别疑似具有标准基因检测未识别的遗传病因的妊娠中的主要遗传异常。通过完成目标 1，我们将能够评估 WES 在产前人群中的表现，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。这些信息将用于制定将 WES 引入产科环境的伦理框架，以及一系列考虑因素，以纳入决策辅助、咨询方案和定量调查，以便在未来的早期外显子组测序研究中使用。该提案的结果是实现我的长期目标的第一步，即建立一套最佳实践来指导未来实施新的和创新的基因组技术以造福家庭。