A complete reference genome improves analysis of human genetic variation

• DOI: 10.1126/science.abl3533
• Publication Date: 2022-03-31T17:57:56Z
• Authors: Sergey Aganezov; Stephanie M. Yan; Daniela C. Soto; Melanie Kirsche; Samantha Zarate; Pavel Avdeyev; Dylan J. Taylor; Kishwar Shafin; Alaina Shumate; Chunlin Xiao; Justin Wagner; Jennifer McDaniel; Nathan D. Olson; Michael E. G. Sauria; Mitchell R. Vollger; Arang Rhie; Melissa Meredith; Skylar Martin; Joyce Lee; Sergey Koren; Jeffrey A. Rosenfeld; Benedict Paten; Ryan Layer; Chen-Shan Chin; Fritz J. Sedlazeck; Nancy F. Hansen; Danny E. Miller; Adam M. Phillippy; Karen H. Miga; Rajiv C. McCoy; Megan Y. Dennis; Justin M. Zook; Michael C. Schatz
• Keywords: Structural Variation; Spurious relationship

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