RT Journal Article
SR Electronic
T1 CRISPR-based targeted haplotype-resolved assemblies of a megabase region
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.21.477044
DO 10.1101/2022.01.21.477044
A1 Taotao Li
A1 Duo Du
A1 Dandan Zhang
A1 Jiakang Ma
A1 Mengyu Zhou
A1 Weida Meng
A1 Zelin Jin
A1 Yicheng Lin
A1 Ziqiang Chen
A1 Haozhe Yuan
A1 Jue Wang
A1 Shulong Dong
A1 Shaoyang Sun
A1 Wenjing Ye
A1 Boshen Li
A1 Zhao Zhang
A1 Zhi Xie
A1 Wenqing Qiu
A1 Yun Liu
YR 2022
UL http://biorxiv.org/content/early/2022/01/23/2022.01.21.477044.abstract
AB 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 de novo assemblies of targeted genomic regions with the CRISPR-based enrichment. Compared to the results from haplotype-resolved genome assemblies, our targeted approach achieved comparable completeness and accuracy with greatly reduced computing complexity, sequencing cost, as well as the amount of starting materials. Moreover, using the targeted assembled personal haplotypes as the reference both improves the quantification accuracy for sequencing data and enables allele-specific functional genomics analyses. 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.Competing Interest StatementThe authors have declared no competing interest.