Targeted and complete genomic sequencing of the Major Histocompatibility Complex in haplotypic form of individual heterozygous samples

The human Major Histocompatibility Complex (MHC) is an approximately 4Mb 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 any heterozygous sample, using long-read sequencing technologies. Our approach is validated using two reference samples, two family trios, and a random sample. 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.