The overall goal of this proposed project is to systematically develop culturally appropriate model ethics guidelines for conducting genetics and genomics research (GGR) in Uganda.

The lack of American Indian and Alaska Native professionals in genomic sciences today highlights the tremendous need for effective training and research programs to prepare the next generation of Native students to be successful in their pursuit of careers in genetics research. Early and meaningful exposure to degree programs and research experiences are critical for the inclusion and advancement of Native students in establishing pathways toward careers in genomics.

Project Summary The breakneck pace of development towards potential uses of germline gene editing (GGE) in medicine raises some very crucial ethical questions. Though much research still needs to be done before GGE will be safe for use on humans, the technology has progressed very rapidly over the past few years. Among the most pressing of the ethical issues raised by GGE are those concerning human subjects research. Future clinical trials will confront novel ethical conundrums that are difficult to resolve given current guidelines.

While newborn screening (NBS) programs have saved the lives of thousands of children with inherited disorders, the future success of this vital public health program depends on the ability to accurately assess and balance the benefits and harms of screening. The ongoing development of new testing technologies increases the number of disorders screened, which generates more false positive NBS results. Despite decades of research, the scope and magnitude of harms from false positive NBS results remain poorly understood.

As concerns for border security increase, policymakers are turning to genomics as a biometric for tracing individuals entering the country, identifying missing migrants' remains, processing refugee claims, and screening for human trafficking. Increasingly, genomic information is a part of legislation and policy as a universal and sustainable biometric. Genetic verification of claimed relationships is required for some refugees and proposed legislation would expand this practice.

While the value of identifying individuals in the population who carry `actionable' variants and screening their relatives (i.e. cascade screening) is widely acknowledged, there are numerous barriers in implementing this process and studying the optimal approaches for doing this. First, the feasibility of returning genetic results is complex as it depends on many issues, including the community expectations, consent form language, local IRB considerations, and logistical, feasibility, and cost issues, among others.

A major challenge for precision medicine research is including historically under-represented groups in numbers sufficient to ensure statistically valid inferences of the influence of relevant risk factors, including genetic contributions to disease risk. Precision medicine researchers have recognized the critical need to enhance diversity and have implemented a wide variety of approaches to achieve this.

As genomic sequence data are being produced faster and at lower cost, the most significant challenge in clinical genetic testing today is variant classification. Currently, there are marked differences in variant classification among clinical laboratories, with clinically significant discrepancies in 29% of variants interpreted. Variants that were previously categorized as pathogenic are now known to be benign with the increasing availability of more ethnically diverse reference data, and this is issue is more common for individuals of non-European ancestry.

Candidate: Kayte Spector-Bagdady, JD, MBE, is an attorney and medical ethicist focused on the governance of secondary research use of human specimens and genetic data. Her long-term career goal is to become an independent investigator leading the development, conduct, and translation of mixed methods ethical, legal, and social implications research into improved genetic data-sharing governance. Research Context: “Precision medicine” and other advances in genetic research offer opportunities to improve diagnosis and therapy for millions of patients.

A large and highly heterogeneous group of individuals conducts genetic and genomic research outside of traditional corporate and academic settings. They can be an important source of innovation, but their activities largely take place beyond the purview of existing regulatory systems for promoting safe and ethical practices. Historically the gene-targeting technology available for non-traditional biology (NTB) experiments has been limited, and therefore they have attracted little regulatory attention.