Targeted haplotype-resolved assembly provides insights into allele-specific regulation of the MHC region

We implemented targeted haplotype-resolved assembly of MHC region, amethod combining CRISPR/Cas9 targeted enrichment of high-molecular weight(HMW) MHC DNA, followed by 10x Genomics linked-reads sequencing and PacBiohigh-fidelity (HiFi) reads sequencing.Two fully phased haplotypeswith high accuracy and integrity were generated without using parent-child trioinformation. We further discovered and varied the allele-specific methylation andexpression events spanning the MHC region using the haplotype reference.