Early Genomic Diagnosis

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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.