PROJECT SUMMARY / ABSTRACT The Human Pangenome Reference Consortium (HPRC) aims to expand the human reference genome to include individuals from globally diverse backgrounds. This project is expected to provide a new reference resource for human genetics and biomedicine that better represents global human genomic diversity. The HPRC is deploying novel third generation sequencing technologies to generate high quality genomes telomere-to-telomere at production scale. Yet, there was no scholarly or financial investment made in the ethical, legal, and social implications (ELSI) inherent in achieving that goal. This administrative supplement will add a rigorous and formal ELSI component to HPRC’s ongoing technical and scientific efforts. It will embed scholars and experts from the appropriate disciplines into every aspect of the project. This proposal was developed in direct response to specific recommendations made by the HPRC’s Scientific Advisory Board (SAB), which noted in January 2021 that ELSI issues must be anticipated and addressed in the early stages of the project, to foster trust and promote inclusion. The SAB also recognized the importance of incorporating lessons learned from previous high-profile projects in human population genetics, which can be accomplished by identifying and responding to ELSI questions as key decision points emerge in the project. Building on initial efforts of project advisors, we will create an “embedded ELSI” team to work with the HPRC leadership and investigators as a supplement to NHGRI grant 5U01-HG010971 (David Haussler, UC, Santa Cruz, PI). The proposed work is within the scope of the original project aims; however, this supplement will help clarify the objectives of the project with regard to representation of human genomic diversity and will work to overcome concerns raised by the development of a reference genome that reflects a broad range of human diversity. The ELSI team will be led by four experienced principal investigators: Barbara Koenig (UCSF), Robert Cook-Deegan (Arizona State), Nanibaa’ Garrison (UCLA), Karen Miga (UC Santa Cruz), and a Co-Investigator to direct the team’s research initiatives, Alice Popejoy (UC Davis). To accomplish its overarching objectives, the team will convene an Ethics Working Group (EWG) with additional experts in relevant disciplines, which will include research ethics, law, social sciences, demography, and population genetics. The EWG will meet regularly for one year, offering the HPRC team advice in real time through participation in standing working group calls and will provide guidance about concerns—both anticipated and unanticipated—related to consent procedures, ethical and scientific selection of study samples, engagement of communities, and definition(s) of diversity to be used selecting and reporting on genetic diversity. It will inventory parallel projects going on globally, and it will prepare a list of topics and background materials for a subsequent worksh...