The Human Pangenome Project: a global resource to map genomic diversity
Ting Wang, Lucinda Antonacci-Fulton, Kerstin Howe, Heather A. Lawson, Julian Lucas, Adam M. Phillippy, Alice B. Popejoy, Mobin Asri, Caryn Carson, Mark Chaisson, Xian Chang, Robert Cook‐Deegan, Adam L. Felsenfeld, Robert S. Fulton, Erik Garrison, Nanibaa’ A. Garrison, Tina A. Graves-Lindsay, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Daofeng Li, Tobias Marschall, Joshua F. McMichael, Adam M. Novak, Deepak Purushotham, Valérie Schneider, Baergen I. Schultz, Michael W. Smith, Heidi J. Sofia, Tsachy Weissman, Paul Flicek, Heng Li, Karen H. Miga, Benedict Paten, Erich D. Jarvis, Ira M. Hall, Evan E. Eichler, David Haussler
Abstract
The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene-disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.