A complete reference genome improves analysis of human genetic variation

被引：212

作者：

Aganezov, Sergey ^{[1
]}

Yan, Stephanie M. ^{[2
]}

Soto, Daniela C. ^{[3
]}

Kirsche, Melanie ^{[1
]}

Zarate, Samantha ^{[1
]}

Avdeyev, Pavel ^{[4
]}

Taylor, Dylan J. ^{[2
]}

Shafin, Kishwar ^{[5
]}

Shumate, Alaina ^{[6
]}

Xiao, Chunlin ^{[7
]}

Wagner, Justin ^{[8
]}

McDaniel, Jennifer ^{[8
]}

Olson, Nathan D. ^{[8
]}

Sauria, Michael E. G. ^{[2
]}

Vollger, Mitchell R. ^{[9
]}

Rhie, Arang ^{[4
]}

Meredith, Melissa ^{[5
]}

Martin, Skylar ^{[10
,11
]}

Lee, Joyce ^{[12
]}

Koren, Sergey ^{[4
]}

Rosenfeld, Jeffrey A. ^{[13
]}

Paten, Benedict ^{[5
]}

Layer, Ryan ^{[10
,11
]}

Chin, Chen-Shan ^{[14
]}

Sedlazeck, Fritz J. ^{[15
]}

Hansen, Nancy F. ^{[16
]}

Miller, Danny E. ^{[9
,17
,18
]}

Phillippy, Adam M. ^{[4
]}

Miga, Karen H. ^{[5
]}

McCoy, Rajiv C. ^{[2
]}

Dennis, Megan Y. ^{[3
]}

Zook, Justin M. ^{[8
]}

Schatz, Michael C. ^{[1
,2
,19
]}

机构：

[1] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA

[3] Univ Calif Davis, Dept Biochem & Mol Med, Genome Ctr, MIND Inst, Davis, CA 95616 USA

[4] NHGRI, Genome Informat Sect, Bethesda, MD 20892 USA

[5] Univ Calif Santa Cruz, UC Santa Cruz Genom Inst, Santa Cruz, CA 95064 USA

[6] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA

[7] Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA

[8] NIST, Gaithersburg, MD 20899 USA

[9] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[10] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA

[11] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA

[12] Bionano Genom, San Diego, CA USA

[13] Canc Inst New Jersey, New Brunswick, NJ USA

[14] DNAnexus, Mountain View, CA USA

[15] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[16] NHGRI, Comparat Genom Anal Unit, Rockville, MD USA

[17] Univ Washington, Dept Pediat, Div Genet Med, Seattle, WA 98195 USA

[18] Seattle Childrens Hosp, Seattle, WA USA

[19] Cold Spring Harbor Lab, Simons Ctr Quantitat Biol, POB 100, Cold Spring Harbor, NY 11724 USA

来源：

SCIENCE | 2022年 / 376卷 / 6588期

关键词：

SEGMENTAL DUPLICATIONS; MUTATIONS; SEQUENCE; DIVERSITY; ANCESTRY; MAP;

D O I：

10.1126/science.abl3533

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：54 / +

页数：113

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