Journal Article

A draft human pangenome reference

Ebler, Jana, Prins, Pjotr, Billis, Konstantinos, Zimin, Aleksey V., Mountcastle, Jacquelyn, Fairley, Susan, Thibaud-Nissen, Françoise, Lu, Tsung-Yu, Markello, Charles, Frankish, Adam, Sofia, Heidi J., Mwaniki, Moses Njagi, Guarracino, Andrea, Harvey, William T., Popejoy, Alice B., Monlong, Jean, Giron, Carlos Garcia, Wang, Ting, Pesout, Trevor, Walenz, Brian, Gao, Yan, Paten, Benedict, Tomlinson, Chad, Sibbesen, Jonas A., Koenig, Barbara A., Colonna, Vincenza, Rautiainen, Mikko, Rhie, Arang, Flicek, Paul, Nurk, Sergey, Lucas, Julian K., Abel, Haley J., Doerr, Daniel, Antonacci-Fulton, Lucinda L., Miga, Karen H., Kolesnikov, Alexey, Felsenfeld, Adam L., Cook, Daniel E., Eizenga, Jordan M., Abou Tayoun, Ahmad N., Tricomi, Francesca Floriana, Smith, Michael W., Chang, Pi-Chuan, Belyaeva, Anastasiya, Regier, Allison A., Garrison, Nanibaa’ A., Garg, Shilpa, Magalhães, Hugo, Groza, Cristian, Hoekzema, Kendra, Marco-Sola, Santiago, Wood, Jonathan M. D., Phillippy, Adam M., Asri, Mobin, Chu, Justin, Sirén, Jouni, Lu, Shuangjia, Martin, Fergal J., Cheng, Haoyu, Chaisson, Mark J. P., Lee, HoJoon, Cody, Sarah, Jarvis,

2023

Overview

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1 . These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample. An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/15 / 45/23 / 45/91 / 631/114/2785 / 631/208/212/2302 / 631/208/727/728 / 631/61/212 / Accuracy / Alleles / Assemblies / Base pairs / Biochemistry, Molecular Biology / Chromosomes / Cohort Studies / Consortia / Diploids / Diploidy / Genetic diversity / Genetic Variation / Genome, Human - genetics / Genomes / Genomics / Genomics - standards / Haplotypes / Haplotypes - genetics / Humanities and Social Sciences / Humans / Life Sciences / multidisciplinary / Nucleotide sequence / Reference Standards / Ribosomal DNA / Science / Science (multidisciplinary) / Sequence Analysis, DNA