Contribution of CRISPRable DNA to human complex traits

Ranran Zhai; Chenqing Zheng; Zhijian Yang; Ting Li; Jiantao Chen; Xia Shen

doi:10.1038/s42003-022-03969-7

Contribution of CRISPRable DNA to human complex traits

Ranran Zhai, Chenqing Zheng, Zhijian Yang, Ting Li, Jiantao Chen, Xia Shen

Deanery of Molecular, Genetic and Population Health Sciences

Research output: Contribution to journal › Review article › peer-review

Abstract

CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes' protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.

Original language	English
Pages (from-to)	1111
Journal	Communications biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03969-7
Publication status	Published - 20 Oct 2022

Keywords

Humans
CRISPR-Cas Systems
DNA/genetics
Gene Editing/methods
Genomics
Multifactorial Inheritance

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10.1038/s42003-022-03969-7Licence: Creative Commons: Attribution (CC-BY)

Contribution of CRISPRable DNA to human complex traitsFinal published version, 4.28 MBLicence: Creative Commons: Attribution (CC-BY)

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title = "Contribution of CRISPRable DNA to human complex traits",

abstract = "CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes' protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.",

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T1 - Contribution of CRISPRable DNA to human complex traits

AU - Zhai, Ranran

AU - Zheng, Chenqing

AU - Yang, Zhijian

AU - Li, Ting

AU - Chen, Jiantao

AU - Shen, Xia

PY - 2022/10/20

Y1 - 2022/10/20

N2 - CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes' protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.

AB - CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes' protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.

KW - Humans

KW - CRISPR-Cas Systems

KW - DNA/genetics

KW - Gene Editing/methods

KW - Genomics

KW - Multifactorial Inheritance

U2 - 10.1038/s42003-022-03969-7

DO - 10.1038/s42003-022-03969-7

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C2 - 36266475

VL - 5

SP - 1111

JO - Communications biology

JF - Communications biology

SN - 2399-3642

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ER -

Contribution of CRISPRable DNA to human complex traits

Abstract

Keywords

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