A refined characterization of large-scale genomic differences in the first complete human genome

Author:

Yang XiangyuORCID,Wang Xuankai,Zou Yawen,Zhang Shilong,Xia Manying,Vollger Mitchell R.ORCID,Chen Nae-ChyunORCID,Taylor Dylan J.ORCID,Harvey William T.ORCID,Logsdon Glennis A.ORCID,Meng Dan,Shi JunfengORCID,McCoy Rajiv C.ORCID,Schatz Michael C.ORCID,Li WeidongORCID,Eichler Evan E.ORCID,Lu QingORCID,Mao YafeiORCID

Abstract

AbstractThe first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release was a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet. Here, we identify 590 discrepant regions (∼226 Mbp) in total. In addition to the previously reported ‘non-syntenic’ regions, we identify 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool (SynPlotter). The discrepant regions (∼20.4 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where copy number variation are likely associated with various human disease and disease susceptibility, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region—theKLRCgene cluster—shows that the depletion ofKLRC2by a single deletion event is associated with natural killer cell differentiation in ∼20% of humans. Meanwhile, the rapid amino acid replacements within KLRC3 is consistent with the action of natural selection during primate evolution. Our study furthers our understanding of the large-scale structural variation differences between these two crucial human reference genomes and future interpretation of studies of human genetic variation.

Publisher

Cold Spring Harbor Laboratory

Reference83 articles.

1. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409 (2001).

2. The Sequence of the Human Genome

3. The UCSC genome browser database: 2021 update;Nucleic Acids Res,2021

4. The complete sequence of a human genome

5. Complete genomic and epigenetic maps of human centromeres

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