scholarly journals The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 978 ◽  
Author(s):  
Shiina ◽  
Blancher

Among the non-human primates used in experimental medicine, cynomolgus macaques (Macaca fascicularis hereafter referred to as Mafa) are increasingly selected for the ease with which they are maintained and bred in captivity. Macaques belong to Old World monkeys and are phylogenetically much closer to humans than rodents, which are still the most frequently used animal model. Our understanding of the Mafa genome has progressed rapidly in recent years and has greatly benefited from the latest technical advances in molecular genetics. Cynomolgus macaques are widespread in Southeast Asia and numerous studies have shown a distinct genetic differentiation of continental and island populations. The major histocompatibility complex of cynomolgus macaque (Mafa MHC) is organized in the same way as that of human, but it differs from the latter by its high degree of classical class I gene duplication. Human polymorphic MHC regions play a pivotal role in allograft transplantation and have been associated with more than 100 diseases and/or phenotypes. The Mafa MHC polymorphism similarly plays a crucial role in experimental allografts of organs and stem cells. Experimental results show that the Mafa MHC class I and II regions influence the ability to mount an immune response against infectious pathogens and vaccines. MHC also affects cynomolgus macaque reproduction and impacts on numerous biological parameters. This review describes the Mafa MHC polymorphism and the methods currently used to characterize it. We discuss some of the major areas of experimental medicine where an effect induced by MHC polymorphism has been demonstrated.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7941
Author(s):  
Shuting Huang ◽  
Xia Huang ◽  
Shuang Li ◽  
Mingjun Zhu ◽  
Min Zhuo

Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.


2016 ◽  
Author(s):  
Julie A. Karl ◽  
Michael E. Graham ◽  
Roger W. Wiseman ◽  
Katelyn E. Heimbruch ◽  
Samantha M. Gieger ◽  
...  

ABSTRACTVery little is currently known about the major histocompatibility complex (MHC) region of cynomolgus macaques (Macaca fascicularis; Mafa) from Chinese breeding centers. We performed comprehensive MHC class I haplotype analysis of 100 cynomolgus macaques from two different centers, with animals from different reported original geographic origins (Vietnamese, Cambodian, and Cambodian/Indonesian mixed-origin). Many of the samples were of known relation to each other (sire, dam, and progeny sets), making it possible to characterize lineage-level haplotypes in these animals. We identified 52 Mafa-A and 74 Mafa-B haplotypes in this cohort, many of which were restricted to specific sample origins. We also characterized full-length MHC class I transcripts using Pacific Biosciences (PacBio) RS II single-molecule real-time (SMRT) sequencing. This technology allows for complete read-through of unfragmented MHC class I transcripts (~1,100 bp in length), so no assembly is required to unambiguously resolve novel full-length sequences. Overall, we identified 313 total full-length transcripts in a subset of 72 cynomolgus macaques from these Chinese breeding facilities; 131 of these sequences were novel and an additional 116 extended existing short database sequences to span the complete open reading frame. This significantly expands the number of Mafa-A, Mafa-B, and Mafa-I full-length alleles in the official cynomolgus macaque MHC class I database. The PacBio technique described here represents a general method for full-length allele discovery and genotyping that can be extended to other complex immune loci such as MHC class II, killer immunoglobulin-like receptors, and Fc gamma receptors.


Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 971 ◽  
Author(s):  
Vorthon Sawaswong ◽  
Elizabeth Fahsbender ◽  
Eda Altan ◽  
Taratorn Kemthong ◽  
Xutao Deng ◽  
...  

Cynomolgus macaques are common across South East Asian countries including Thailand. The National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU) captures wild-borne cynomolgus macaque for research use. Limited information is available on the enteric viruses and possible zoonotic infections into or from cynomolgus macaques. We characterized and compare the fecal virome of two populations; healthy wild-originated captive cynomolgus macaques (n = 43) reared in NPRCT-CU and healthy wild cynomolgus macaques (n = 35). Over 90% of recognized viral sequence reads amplified from feces were from bacterial viruses. Viruses from seven families of mammalian viruses were also detected (Parvoviridae, Anelloviridae, Picornaviridae, Adenoviridae, Papillomaviridae, Herpesviridae, and Caliciviridae). The genomes of a member of a new picornavirus genus we named Mafapivirus, a primate chapparvovirus, and a circular Rep-encoding single-strand (CRESS) DNA virus were also characterized. Higher abundance of CRESS DNA viruses of unknown tropism and invertebrate-tropic ambidensovirus were detected in wild versus captive macaques likely reflecting dietary differences. Short term rearing in captivity did not have a pronounced effect on the diversity of mammalian viruses of wild cynomolgus macaques. This study is the first report of the fecal virome of cynomolgus macaques, non-human primates frequently used in biomedical research and vaccination studies.


Genetics ◽  
1989 ◽  
Vol 122 (3) ◽  
pp. 681-686 ◽  
Author(s):  
A L Hughes ◽  
M Nei

Abstract The major histocompatibility complex (MHC) in humans and chimpanzees includes three classical class I loci, A, B and C, which encode glycoproteins expressed on the surface of all nucleated cells. There are also several nonclassical class I loci including E, which have more limited expression. By analyzing published sequences, we have shown that in exons 4 and 5, A locus alleles from both humans and chimpanzees are much more similar to E than to B or C alleles, whereas in exons 2 and 3 alleles from all three classical class I loci are much more similar to each other than any one is to E. We propose that some 20 million years ago, interlocus recombination led to the formation of a hybrid gene in which exons 2 and 3 were derived from the original A locus and exons 4 and 5 were derived from the E locus. The fact that such an ancient event can still be detected suggests that interlocus recombination is rare in the MHC and does not significantly contribute to MHC polymorphism, which is known to be extremely high. The present finding, however, supports Gilbert's idea that exons in a gene may occasionally be replaced by those from another gene in the evolutionary process.


2019 ◽  
Vol 71 (10) ◽  
pp. 647-663 ◽  
Author(s):  
Nicola D. Potts ◽  
Coraline Bichet ◽  
Laurence Merat ◽  
Edouard Guitton ◽  
Andrew P. Krupa ◽  
...  

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9347
Author(s):  
Xia Huang ◽  
Shijia Li ◽  
Xiaoming Liu ◽  
Shuting Huang ◽  
Shuang Li ◽  
...  

MicroRNAs (miRNAs) are important regulators that fine-tune diverse cellular activities. Cynomolgus macaques (Macaca fascicularis) are used extensively in biomedical and pharmaceutical research; however, substantially fewer miRNAs have been identified in this species than in humans. Consequently, we investigated conserved miRNA profiles in cynomolgus macaques by homology searching and small RNA sequencing. In total, 1,455 high-confidence miRNA gene loci were identified, 408 of which were also confirmed by RNA sequencing, including 73 new miRNA loci reported in cynomolgus macaques for the first time. Comparing miRNA expression with age, we found a positive correlation between sequence conservation and expression levels during miRNA evolution. Additionally, we found that the miRNA gene locations in cynomolgus macaque genome were very flexible. Most were embedded in intergenic spaces or introns and clustered together. Several miRNAs were found in certain gene locations, including 64 exon-resident miRNAs, six splice-site-overlapping miRNAs (SO-miRNAs), and two pairs of distinct mirror miRNAs. We also identified 78 miRNA clusters, 68 of which were conserved in the human genome, including 10 large miRNA clusters predicted to regulate diverse developmental and cellular processes in cynomolgus macaque. Thus, this study not only expands the number of identified miRNAs in cynomolgus macaques but also provides clues for future research on the differences in miRNA repertoire between macaques and humans.


2007 ◽  
Vol 178 (9) ◽  
pp. 5744-5752 ◽  
Author(s):  
Iain Shaw ◽  
Timothy J. Powell ◽  
Denise A. Marston ◽  
Ken Baker ◽  
Andrew van Hateren ◽  
...  
Keyword(s):  
Class I ◽  

1998 ◽  
Vol 48 (5) ◽  
pp. 312-323 ◽  
Author(s):  
I. B. Jakobsen ◽  
Susan R. Wilson ◽  
S. Easteal

1990 ◽  
Vol 55 (3) ◽  
pp. 171-176 ◽  
Author(s):  
Peter R. Shewry ◽  
Saroj Parmar ◽  
Julian Franklin ◽  
Shirley R. Burgess

SummaryA rare recombinant within the multigenic Hor 2 locus of barley was detected by SD-PAGE of hordein fractions from F2 grain from the cross Bomi × P12/3. Analysis of a homozygous F4 line by 2-D IEF/SDS-PAGE showed that recombination between the class I/II and class III subfamilies of genes had occurred, indicating that they are spatially separate within the Hor 2 locus. RFLP analysis using a B hordein-related cDNA clone confirmed that recombination had occurred, while similar analysis using a genomic clone related to γ-type hordein (encoded by the Hor 5/HrdF locus) indicated the order of the two subfamilies of genes on the short arm of chromosome 5, the class I/II genes being closer to the centromere. The results are consistent with the origin of the B hordein gene family from initial duplication of a single ancestral gene to give two genes which diverged to become the ancestors of the class I/II and class III subfamilies. Subsequent cycles of duplication and divergence have resulted in the present high degree of polymorphism.


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