A complete reference genome improves analysis of human genetic variation.

TitleA complete reference genome improves analysis of human genetic variation.
Publication TypeJournal Article
Year of Publication2022
AuthorsAganezov, S, Yan, SM, Soto, DC, Kirsche, M, Zarate, S, Avdeyev, P, Taylor, DJ, Shafin, K, Shumate, A, Xiao, C, Wagner, J, McDaniel, J, Olson, ND, Sauria, MEG, Vollger, MR, Rhie, A, Meredith, M, Martin, S, Lee, J, Koren, S, Rosenfeld, JA, Paten, B, Layer, R, Chin, C-S, Sedlazeck, FJ, Hansen, NF, Miller, DE, Phillippy, AM, Miga, KH, McCoy, RC, Dennis, MY, Zook, JM, Schatz, MC
JournalScience
Volume376
Issue6588
Paginationeabl3533
Date Published2022 Apr
ISSN1095-9203
KeywordsGenetic Variation, Genome, Human, Genomics, Humans, Reference Standards, Sequence Analysis, DNA
Abstract

Compared to its predecessors, the Telomere-to-Telomere CHM13 genome adds nearly 200 million base pairs of sequence, corrects thousands of structural errors, and unlocks the most complex regions of the human genome for clinical and functional study. We show how this reference universally improves read mapping and variant calling for 3202 and 17 globally diverse samples sequenced with short and long reads, respectively. We identify hundreds of thousands of variants per sample in previously unresolved regions, showcasing the promise of the T2T-CHM13 reference for evolutionary and biomedical discovery. Simultaneously, this reference eliminates tens of thousands of spurious variants per sample, including reduction of false positives in 269 medically relevant genes by up to a factor of 12. Because of these improvements in variant discovery coupled with population and functional genomic resources, T2T-CHM13 is positioned to replace GRCh38 as the prevailing reference for human genetics.

DOI10.1126/science.abl3533
Alternate JournalScience
PubMed ID35357935
PubMed Central IDPMC9336181
Grant ListU01 HG010961 / HG / NHGRI NIH HHS / United States
DP2 MH119424 / MH / NIMH NIH HHS / United States
U41 HG010972 / HG / NHGRI NIH HHS / United States
OT2 OD026682 / OD / NIH HHS / United States
R21 HG010548 / HG / NHGRI NIH HHS / United States
U01 HG010971 / HG / NHGRI NIH HHS / United States
U24 HG011853 / HG / NHGRI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States
U24 HG010263 / HG / NHGRI NIH HHS / United States
R01 HG006677 / HG / NHGRI NIH HHS / United States
R35 GM133747 / GM / NIGMS NIH HHS / United States
R00 HG009532 / HG / NHGRI NIH HHS / United States
U01 CA253481 / CA / NCI NIH HHS / United States
R01 HG011274 / HG / NHGRI NIH HHS / United States
U24 HG006620 / HG / NHGRI NIH HHS / United States
R01 HG010485 / HG / NHGRI NIH HHS / United States
R24 DK106766 / DK / NIDDK NIH HHS / United States

Similar Publications