Characterization of large-scale genomic differences in the first complete human genome

Yang, Xiangyu, Wang, Xuankai, Zou, Yawen, Zhang, Shilong, Xia, Manying, Fu, Lianting, Vollger, Mitchell R, Chen, Nae-Chyun, Taylor, Dylan J, Harvey, William T, Logsdon, Glennis A, Meng, Dan, Shi, Junfeng, McCoy, Rajiv C, Schatz, Michael C, Li, Weidong, Eichler, Evan E, Lu, Qing, Mao, Yafei (July 2023) Characterization of large-scale genomic differences in the first complete human genome. Genome Biology, 24 (1). p. 157. ISSN 1474-760X

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Abstract

BACKGROUND: The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is 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. RESULTS: Here, in addition to the previously reported "non-syntenic" regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region-the KLRC gene cluster-show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution. CONCLUSION: Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > Mapping and Rendering organism description > animal bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome > centromere bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome > centromere bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function organism description > animal > mammal > primates > hominids organism description > animal > mammal > primates > hominids > human organism description > animal > mammal organism description > animal > mammal > primates
CSHL Authors:	Schatz, Michael C.
Communities:	CSHL labs > Schatz lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	4 July 2023
Date Deposited:	21 Sep 2023 18:34
Last Modified:	11 Jan 2024 14:58
PMCID:	PMC10320979
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40951

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