Multiple full-length homozygous IGH haplotypes from Mauritian cynomolgus macaques

Background: Nonhuman primates are valuable experimental models for human disease pathology and vaccine design. However, the vast and mostly uncatalogued immunogenomic diversity of typical species adds complexity to the interpretation of experiments and hinders reproducibility. Mauritian cynomolgus macaques (MCM) offer a unique opportunity to circumvent these difficulties, due to their restricted genetic diversity. Results: We assembled high-quality immunoglobulin heavy chain (IGH) haplotypes from long-read genomic sequencing of 13 MCM. Four animals were homozygous for IGH, yielding 3 distinct haplotypes, termed H1, H2, and H3. IGH haplotype H1 was observed in two of the homozygotes and 5 additional heterozygous animals, accounting for half of the assemblies recovered. H1 shares only 83% average sequence identity with the IGH locus of the rhesus macaque reference genome, in addition to numerous large structural variations. The other two homozygous haplotypes exhibited considerable variation, including a 60 kilobase (Kbp) deletion and 200 Kbp insertion relative to H1. Furthermore, we annotated the IG gene content from all complete MCM IGH assemblies and found 288 functional IGHV alleles, of which 94 (33%) were not in existing databases. We also identified 68 functional IGHD alleles, 11 functional IGHJ alleles, and 33 functional constant gene alleles across all 5 isotypes. Conclusions: We identified multiple common and genetically diverse IGH haplotypes within MCM and provide high-quality reference assemblies and annotations for these to facilitate future work with this important animal model.