RT Journal Article
SR Electronic
T1 A complete reference genome improves analysis of human genetic variation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.12.452063
DO 10.1101/2021.07.12.452063
A1 Sergey Aganezov
A1 Stephanie M. Yan
A1 Daniela C. Soto
A1 Melanie Kirsche
A1 Samantha Zarate
A1 Pavel Avdeyev
A1 Dylan J. Taylor
A1 Kishwar Shafin
A1 Alaina Shumate
A1 Chunlin Xiao
A1 Justin Wagner
A1 Jennifer McDaniel
A1 Nathan D. Olson
A1 Michael E.G. Sauria
A1 Mitchell R. Vollger
A1 Arang Rhie
A1 Melissa Meredith
A1 Skylar Martin
A1 Joyce Lee
A1 Sergey Koren
A1 Jeffrey A. Rosenfeld
A1 Benedict Paten
A1 Ryan Layer
A1 Chen-Shan Chin
A1 Fritz J. Sedlazeck
A1 Nancy F. Hansen
A1 Danny E. Miller
A1 Adam M. Phillippy
A1 Karen H. Miga
A1 Rajiv C. McCoy
A1 Megan Y. Dennis
A1 Justin M. Zook
A1 Michael C. Schatz
YR 2021
UL http://biorxiv.org/content/early/2021/07/13/2021.07.12.452063.abstract
AB Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 Mbp of sequence, corrects thousands of structural errors, and unlocks the most complex regions of the human genome to clinical and functional study. Here we demonstrate how the new reference universally improves read mapping and variant calling for 3,202 and 17 globally diverse samples sequenced with short and long reads, respectively. We identify hundreds of thousands of novel variants per sample—a new frontier for evolutionary and biomedical discovery. Simultaneously, the new reference eliminates tens of thousands of spurious variants per sample, including up to 12-fold reduction of false positives in 269 medically relevant genes. The vast improvement in variant discovery coupled with population and functional genomic resources position T2T-CHM13 to replace GRCh38 as the prevailing reference for human genetics.One Sentence Summary The T2T-CHM13 reference genome universally improves the analysis of human genetic variation.Competing Interest StatementC.S.C. is an employee of DNAnexus. J.L. is an employee of Bionano Genomics. S.A. is an employee of Oxford Nanopore Technologies. F.J.S has received travel funds and spoken at PacBio and Oxford Nanopore Technologies events. S.K. has received travel funds to speak at symposia organized by Oxford Nanopore Technologies.