A significant proportion of patients who pursue testing for BRCA gene alterations are of reproductive age. Many are actively engaged in decisions about family planning or will be in the future. A prime concern of this population is minimizing the impact of hereditary cancer on their children. Genetically-enhanced assisted reproductive technologies (ART), such as preimplantation genetic diagnosis (PGD), as well as prenatal diagnosis (PND) followed by consideration of selective abortion, may enable individuals and couples to avoid passing genetic mutations on to their children.
Primary care physicians have almost no training in genetics, nor in the ethical, legal and social implications (ELSI) of genetic testing, diagnosis and therapy. Further, mere provision of curricular content fails to impact physician behavior. However, programs with elements that are based on established educational and adult learning principles have been shown to effective in affecting behavioral change.
One of the intended goals of the ELSI CEER program is to provide guidance on policy issues that arise from novel genetic and genomic science and applications. This focus, however, misses epigenetic processes. Epigenetics involves the point at which nature and nurture intersect via discrete environmentally imposed modifications to the genome. These modifications include DNA methylation, and their distribution across the genome creates cell-specific epigenomes that control cell-specific expression patterns.
The specific aim of this project is to determine what criteria should govern return of individual results of pediatric genomic research, using analysis of US law and international guidelines regarding decision making for and by minors as the foundation. This issue, which has received remarkably little attention, must be resolved if this research, which is vital to understanding the contributions of genetic variation to the health of children, is to proceed.
Genetic researchers are rapidly adopting methods of whole exome and whole genome sequencing to identify the hereditary bases for human disease as the cost of sequencing rapidly declines and the pipelines for analysis and databases of normal variation become available and more robust. Although most researchers have focused on particular diseases, comprehensive genome analysis also provides data about susceptibility to hereditary conditions beyond the original study aims.
Exome sequencing and whole genome sequencing (ES/WGS) are rapidly emerging as important tools in human genetics research. Unlike conventional approaches, ES/WGS can putatively identify all functional variation in the entire coding sequence of a research participant. As a result, both the number and scope of findings with clinical utility are substantially greater than anticipated by existing guidelines and traditional approaches to return of results.
When individuals are queried about whether or not they wish to receive individual research results about themselves that are discovered in the course of genomic research, the majority indicate that they prefer receiving all results, including those that are of limited validity and actionability. These preferences are in sharp contrast to the recommendations of experts who are wary of the potential for confusion and outright harm if questionable results are returned, and thus generally recommend returning only results of high validity and actionability.
The ability to utilize biospecimens collected at the time of birth for research that integrates genetic variation, social and environmental exposures, and health outcomes may be an invaluable resource in promoting epigenetic approaches to disease prevention and health promotion. There are a growing number of perinatal biobanks in the US and globally, including many focused on preventing prematurity, specific childhood conditions, or birth defects.
The University of Utah Center for Excellence in ELSI Research (UCEER) will conduct strategic planning for ELSI research, training and mentoring, and conduct two pilot projects. The focus of the UCEER will be population screening for genetic conditions in the health care of women and children. Our specific focus will be prenatal genetic screening and newborn screening. We will build on our strengths and experience to develop a collaborative, transdisciplinary center for research and training in ELSI issues.
A big data ecosystem is evolving in our society in which people may have, or feel they have, little control over the flow of their personal health information, and thus their privacy. Further, although there has been significant discussion related to big data and privacy at the highest levels of government, there is little consensus among scholars and stakeholders as to what privacy actually is, not to mention a lack of data from individuals as to personal conceptions of privacy.