The Case of a Missing HLA-B Gene

Abstract

The Major Histocompatibility Complex (MHC) of human chromosome 6 contains multiple genes critical for immunity. The exceptional polymorphism of this genomic region that establishes and maintains immune diversity can be technically challenging to characterise and analyse. In this study, we present a family where the mother and one of her children have no HLA-B allele in common, implying the absence of HLA-B from the maternal haplotype. Homozygosity of the mother and child was confirmed using three independent PCR-based methods and high throughput DNA sequencing. Through probe-based MHC region enrichment, sequencing, and read mapping, we located the breakpoints of a large (36.5 kbp) deletion encompassing the entire HLA-B gene. Accordingly, the deletion was present on the maternal haplotype and transmitted to the child. This study demonstrates strategies for locating large deletions in complex genomic regions and highlights the dynamic nature of MHC structure and variation.