RT Journal
A1 de Groot, Nanine
A1 van der Wiel, Marit
A1 Le, Ngoc Giang
A1 de Groot, Natasja G.
A1 Bruijnesteijn, Jesse
A1 Bontrop, Ronald E.
T1 Unraveling the architecture of major histocompatibility complex class II haplotypes in rhesus macaques
JF Genome Research 
JO Genome Research 
YR 2024 
FD November 01 
VO 34 
IS 11 
SP 1811 
OP 1824 
DO 10.1101/gr.278968.124 
UL http://genome.cshlp.org/content/34/11/1811.abstract 
AB The regions in the genome that encode components of the immune system are often featured by polymorphism, copy number variation, and segmental duplications. There is a need to thoroughly characterize these complex regions to gain insight into the impact of genomic diversity on health and disease. Here we resolve the organization of complete major histocompatibility complex (MHC) class II regions in rhesus macaques by using a long-read sequencing strategy (Oxford Nanopore Technologies) in concert with adaptive sampling. In particular, the expansion and contraction of the primate DRB-region appear to be a dynamic process that involves the rearrangement of different cassettes of paralogous genes. These chromosomal recombination events are propagated by a conserved pseudogene, DRB6, which features the integration of two retroviral elements. In contrast, the DRA locus appears to be protected from rearrangements, which may be owing to the presence of an adjacently located truncated gene segment, DRB9. With our sequencing strategy, the annotation, evolutionary conservation, and potential function of pseudogenes can be reassessed, an aspect that was neglected by most genome studies in primates. Furthermore, our approach facilitates the characterization and refinement of an animal model essential to study human biology and disease.