Original Paper

Immunogenetics

, Volume 60, Issue 12, pp 737-748

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Comparative genetics of a highly divergent DRB microsatellite in different macaque species

  • Nanine de GrootAffiliated withDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre Email author 
  • , Gaby G. M. DoxiadisAffiliated withDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre
  • , Annemiek J. M. de Vos-RouwelerAffiliated withDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre
  • , Natasja G. de GrootAffiliated withDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre
  • , Ernst J. VerschoorAffiliated withDepartment of Virology, Biomedical Primate Research Centre
  • , Ronald E. BontropAffiliated withDepartment of Comparative Genetics and Refinement, Biomedical Primate Research Centre

Abstract

The DRB region of the major histocompatibility complex (MHC) of cynomolgus and rhesus macaques is highly plastic, and extensive copy number variation together with allelic polymorphism makes it a challenging enterprise to design a typing protocol. All intact DRB genes in cynomolgus monkeys (Mafa) appear to possess a compound microsatellite, DRB-STR, in intron 2, which displays extensive length polymorphism. Therefore, this STR was studied in a large panel of animals, comprising pedigreed families as well. Sequencing analysis resulted in the detection of 60 Mafa-DRB exon 2 sequences that were unambiguously linked to the corresponding microsatellite. Its length is often allele specific and follows Mendelian segregation. In cynomolgus and rhesus macaques, the nucleotide composition of the DRB-STR is in concordance with the phylogeny of exon 2 sequences. As in humans and rhesus monkeys, this protocol detects specific combinations of different DRB-STR lengths that are unique for each haplotype. In the present panel, 22 Mafa-DRB region configurations could be defined, which exceeds the number detected in a comparable cohort of Indian rhesus macaques. The results suggest that, in cynomolgus monkeys, even more frequently than in rhesus macaques, new haplotypes are generated by recombination-like events. Although both macaque species are known to share several identical DRB exon 2 sequences, the lengths of the corresponding microsatellites often differ. Thus, this method allows not only fast and accurate DRB haplotyping but may also permit discrimination between highly related macaque species.

Keywords

MHC Nonhuman primates Evolution Microsatellites Macaques