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CRISPR-based targeted haplotype-resolved assembly of a megabase region

Author

Listed:
  • Taotao Li

    (Fudan University
    Fudan University)

  • Duo Du

    (Fudan University
    Fudan University)

  • Dandan Zhang

    (Fudan University
    Fudan University)

  • Yicheng Lin

    (Fudan University
    Fudan University)

  • Jiakang Ma

    (Fudan University
    Fudan University)

  • Mengyu Zhou

    (Fudan University
    Fudan University)

  • Weida Meng

    (Fudan University
    Fudan University)

  • Zelin Jin

    (Fudan University
    Fudan University)

  • Ziqiang Chen

    (Fudan University
    Fudan University)

  • Haozhe Yuan

    (Fudan University
    Fudan University)

  • Jue Wang

    (Fudan University
    Fudan University)

  • Shulong Dong

    (Fudan University
    Fudan University)

  • Shaoyang Sun

    (Fudan University)

  • Wenjing Ye

    (Fudan University)

  • Bosen Li

    (Fudan University)

  • Houbao Liu

    (Fudan University)

  • Zhao Zhang

    (Fudan University)

  • Yuchen Jiao

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Zhi Xie

    (Sun Yat-sen University)

  • Wenqing Qiu

    (Fudan University
    Fudan University)

  • Yun Liu

    (Fudan University
    Fudan University)

Abstract

Constructing high-quality haplotype-resolved genome assemblies has substantially improved the ability to detect and characterize genetic variants. A targeted approach providing readily access to the rich information from haplotype-resolved genome assemblies will be appealing to groups of basic researchers and medical scientists focused on specific genomic regions. Here, using the 4.5 megabase, notoriously difficult-to-assemble major histocompatibility complex (MHC) region as an example, we demonstrated an approach to construct haplotype-resolved assembly of the targeted genomic region with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assembly, our targeted approach achieved comparable completeness and accuracy with reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal MHC haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses of the MHC region. Given its highly efficient use of resources, our approach can greatly facilitate population genetic studies of targeted regions, and may pave a new way to elucidate the molecular mechanisms in disease etiology.

Suggested Citation

  • Taotao Li & Duo Du & Dandan Zhang & Yicheng Lin & Jiakang Ma & Mengyu Zhou & Weida Meng & Zelin Jin & Ziqiang Chen & Haozhe Yuan & Jue Wang & Shulong Dong & Shaoyang Sun & Wenjing Ye & Bosen Li & Houb, 2023. "CRISPR-based targeted haplotype-resolved assembly of a megabase region," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35389-w
    DOI: 10.1038/s41467-022-35389-w
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    References listed on IDEAS

    as
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