Identification of MhcMafa-DRB Alleles in a Cohort of Cynomolgus Macaques of Vietnamese Origin

摘要

Cynomolgus macaques have been used widely to build a research model of infectious and chronic diseases, as well as in transplantation studies, where disease susceptibility and/or resistance are associated with the major histocompatibility complex (MHC). To better elucidate polymorphisms and genetic differences in the Mafa-DRB locus, and facilitate the experimental use of cynomolgus macaques, we used pool screening combined with cloning and direct sequencing of polymerase chain reaction products to characterize MhcMafa-DRB gene alleles in 153 Vietnamese cynomolgus macaques. We identified 30 Mafa-DRB alleles belonging to 17 allelic lineages, including four novel sequences that had not been documented in earlier reports. The highest frequency allele was Mafa-DRB*W27:04, which was present in 7 of 35 (20%) monkeys. The next most frequent alleles were Mafa-DRB*3:07 and Mafa-DRB*W7:01, which were detected in 5 of 35 (14.3%) and 4 of 35 (11.4%) of the monkeys, respectively. The high-frequency alleles in this Vietnamese population may be high priority targets for additional characterization of immune functions. Only the DRB1*03 and DRB1*10 lineages were also present in humans, whereas the remaining alleles were monkey-specific lineages. We found 25 variable sites by aligning the deduced amino acid sequences of 29 identified alleles. Evolutionary and population analyses based on these sequences showed that human, rhesus, and cynomolgus macaques share several Mhc-DRB lineages and the shared polymorphisms in the DRB region may be attributable to the existence of interbreeding between rhesus and cynomolgus macaques. This information will promote the understanding of MHC diversity and polymorphism in cynomolgus macaques and increase the value of this species as a model for biomedical research.