A complete reference genome improves analysis of human genetic variation-Reference-Cited by-同舟云学术

A complete reference genome improves analysis of human genetic variation

Published:2022-04 Issue:6588 Volume:376 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Aganezov Sergey¹^ORCID,Yan Stephanie M.²^ORCID,Soto Daniela C.³^ORCID,Kirsche Melanie¹^ORCID,Zarate Samantha¹^ORCID,Avdeyev Pavel⁴^ORCID,Taylor Dylan J.²^ORCID,Shafin Kishwar⁵^ORCID,Shumate Alaina⁶^ORCID,Xiao Chunlin⁷^ORCID,Wagner Justin⁸,McDaniel Jennifer⁸^ORCID,Olson Nathan D.⁸^ORCID,Sauria Michael E. G.²^ORCID,Vollger Mitchell R.⁹^ORCID,Rhie Arang⁴^ORCID,Meredith Melissa⁵^ORCID,Martin Skylar¹⁰,Lee Joyce¹¹^ORCID,Koren Sergey⁴^ORCID,Rosenfeld Jeffrey A.¹²^ORCID,Paten Benedict⁵^ORCID,Layer Ryan¹⁰,Chin Chen-Shan¹³^ORCID,Sedlazeck Fritz J.¹⁴^ORCID,Hansen Nancy F.¹⁵^ORCID,Miller Danny E.⁹¹⁶^ORCID,Phillippy Adam M.⁴^ORCID,Miga Karen H.⁵^ORCID,McCoy Rajiv C.²^ORCID,Dennis Megan Y.³^ORCID,Zook Justin M.⁸^ORCID,Schatz Michael C.¹²¹⁷^ORCID

Affiliation:

1. Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.

2. Department of Biology, Johns Hopkins University, Baltimore, MD, USA.

3. Department of Biochemistry and Molecular Medicine, Genome Center, MIND Institute, University of California, Davis, CA, USA.

4. Genome Informatics Section, National Human Genome Research Institute, Bethesda, MD, USA.

5. UC Santa Cruz Genomics Institute, University of California, Santa Cruz, CA, USA.

6. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.

7. National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD, USA.

8. National Institute of Standards and Technology, Gaithersburg, MD, USA.

9. Department of Genome Sciences, University of Washington, Seattle, WA, USA.

10. Department of Computer Science and Biofrontiers Institute, University of Colorado, Boulder, CO, USA.

11. Bionano Genomics, San Diego, CA, USA.

12. Cancer Institute of New Jersey, New Brunswick, NJ, USA.

13. DNAnexus, Mountain View, CA, USA.

14. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

15. Comparative Genomics Analysis Unit, National Human Genome Research Institute, Rockville, MD, USA.

16. Department of Pediatrics, Division of Genetic Medicine, University of Washington and Seattle Children’s Hospital, Seattle, WA, USA.

17. Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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