Comprehensive identification of high-frequency and co-occurring Mafa-DPA1, Mafa-DQA1, Mafa-DRA, and Mafa-DOA alleles in Vietnamese cynomolgus macaques

Abstract

High-frequency alleles and/or co-occurring human leukocyte antigen alleles across loci appear to be more important than individual alleles as markers of disease risk and have clinical value as biomarkers for targeted screening or the development of new disease therapies. To better elucidate the major histocompatibility complex (MHC) background and to facilitate the experimental use of cynomolgus macaques, Mafa-DPA1, Mafa-DQA1, Mafa-DRA, and Mafa-DOA alleles were characterized, and their combinations were investigated in 30 Vietnamese macaques by gene cloning and sequencing. A total of 26 Mafa-DPA1, 18 Mafa-DQA1, 9 Mafa-DRA, and 15 Mafa-DOA alleles, including 7 high-frequency alleles, were identified in this study, respectively. In addition, 15 Mafa-DQA1, 17 Mafa-DPA1, 15 Mafa-DOA, and 2 Mafa-DRA alleles represented novel sequences that had not been documented in earlier studies. Our results also showed that the Vietnamese macaques might be valuable because no less than 30% of the test animals possessed Mafa-DRA*01:02:01 (90%), -DQA1*26:01:03 (37%), -DOA*01:02:07 (34%), and -DQA1*01:03:03 (30%). We previously reported that the combinations of MHC class II alleles, including the combination of DOA*01:02:07-DPA1*02:09 and DOA*01:02:07-DQA1*01:03:03, were detected in 17 and 14% of the animals, respectively. Interestingly, more than two Mafa-DQA1 and Mafa-DPA1 alleles were detected in one animal in this study, which suggested that they might be caused by a chromosomal duplication. If our findings can be validated by other studies, it will further enrich the number of known Mafa-DPA1 and Mafa-DQA1 polymorphisms. Our results identified the co-occurring MHC alleles across loci in a cohort of Vietnamese cynomolgus macaques, which emphasized the value of this species as a model for biomedical research.

Ten novel MHC class II alleles identified in cynomolgus macaques of Vietnamese origin

“…The combinations of MHC class II alleles, DPB1*15:01‐DQB1*06:30‐DRB*W4:03‐DRB*W25:03 , were detected in three Vietnamese cynomolgus macaques. Combined with our previous studies , we conclude that extraordinary MHC II allele sharing is a characteristic feature of Vietnamese cynomolgus macaques. Importantly, the MHC Mamu‐DQB1*06:01 allele associated with faster disease progression in Simian immunodeficiency virus (SIV)‐infected rhesus macaques displays 100% similarity to our Mafa‐DQB1*06:01:01 sequence in this study.…”

Identification of five novel MHC class II alleles in cynomolgus macaques of Vietnamese origin

“…To increase the understanding of genetic differences of MHC class II in cynomolgus macaques, the polymorphism in exons 2 and 3 of Mafa‐DPA1, Mafa‐DQA1 and Mafa‐DRA were investigated in 22 unrelated Vietnamese cynomolgus macaques those were farmed in South China Primate Research and Developmental Center. The same primers and methods were used as described previously . Novel allele sequences were submitted to the GenBank and IPD‐MHC databases .…”