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MHC haplotyping in rhesus and cynomolgus macaques

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Host: Jim Kaufman, jfk31@cam.ac.uk

The Biomedical Primate Research Centre in Rijswijk, The Netherlands, houses breeding colonies of rhesus as well as cynomolgus macaques for biomedical and ethological research, respectively.

The gene products of the Major Histocompatibility complex (MHC) play an important role in immune reactions, and the genes encoding these molecules show a high degree of variability and diversity in humans as well as non-human primates. The classical Mhc genes of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, Mamu/Mafa-A, -B, and -DRB show several levels of complexity, namely allelic variation (polymorphism), copy number variation, the combination of different genes per haplotype (diversity), and transcription level variation as well.

In the past, more than five generations of monkeys of the rhesus macaque breeding colony of Indian origin have been serologically typed, and MHC haplotypes could be defined based on segregation. Nowadays, serology has been replaced by molecular typing methods as genomic exon 2 sequencing (Mamu-DQA1, -DQB1, -DPB1, -DRB) and full-length cDNA analysis (Mamu-A and -B).

Recently, microsatellite typing has been added to the methods that allow haplotyping in an efficient, robust, time saving and inexpensive manner. In such a way, 15 different Mamu-A, 17 –B, and 21 –DRB (haplo)types could be defined within a panel of more than 1000 Indian rhesus macaques which make up a total of 135 different MhcMamu haplotypes. The same typing methods led to the definition of 32 different Mhc haplotypes within the cynomolgus macaque breeding colony of < 200 monkeys.

Our data show that microsatellite typing methods are useful to define Mhc haplotypes for both macaque species. Furthermore, the results demonstrate that the MHC of the cynomolgus macaque appears to consist of unique A/B/DR (haplo)types whereas the MHC of the Indian rhesus macaque seems to be built up by a combination of several A, B, and DR segments.

This talk is part of the Immunology in Pathology series.

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