RT Journal
A1 Hu, Taishan
A1 Mosbruger, Timothy L.
A1 Tairis, Nikolaos G.
A1 Dinou, Amalia
A1 Jayaraman, Pushkala
A1 Sarmady, Mahdi
A1 Brewster, Kingham
A1 Li, Yang
A1 Hayeck, Tristan J.
A1 Duke, Jamie L.
A1 Monos, Dimitri S.
T1 Targeted and complete genomic sequencing of the major histocompatibility complex in haplotypic form of individual heterozygous samples
JF Genome Research 
JO Genome Research 
YR 2024 
FD October 01 
VO 34 
IS 10 
SP 1500 
OP 1513 
DO 10.1101/gr.278588.123 
UL http://genome.cshlp.org/content/34/10/1500.abstract 
AB The human major histocompatibility complex (MHC) is a ∼4 Mb genomic segment on Chromosome 6 that plays a pivotal role in the immune response. Despite its importance in various traits and diseases, its complex nature makes it challenging to accurately characterize on a routine basis. We present a novel approach allowing targeted sequencing and de novo haplotypic assembly of the MHC region in heterozygous samples, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and an African-American sample. We achieved excellent coverage (96.6%–99.9% with at least 30× depth) and high accuracy (99.89%–99.99%) for the different haplotypes. This methodology offers a reliable and cost-effective method for sequencing and fully characterizing the MHC without the need for whole-genome sequencing, facilitating broader studies on this important genomic segment and having significant implications in immunology, genetics, and medicine.