Genetic Typing

Development of sophisticated methods for molecular typing of immunologically important genes in breeding colonies of captive rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques - JRA1

Immunologically important regions in the mammalian genome typically contain large families of highly related genes such as the major histocompatibility complex (MHC) class I and class II gene families or the killer cell immunoglobulin-like receptor (KIR) genes. As an adaptation to combat pathogen infections, the MHC class I/class II and KIR genes of primates evolve rapidly, giving rise to an outstanding degree of allelic polymorphism as well as presence and absence of genes (genomic plasticity ), and leading to so-called "responder" and "non-responder" individuals with respect to infection or vaccination with the pathogen under study or to susceptible or non-susceptible individuals with respect to autoimmune diseases.Molecular techniques for typing of these immunologically important loci are therefore indispensable for any study of infectious and autoimmune diseases.

Rhesus and cynomolgus macaques are frequently used as models of these diseases, yet sophisticated typing techniques for class I and KIR loci are not available. Thus, the objective of this study is to develop methods for the genotyping of these genes. These typing facilitates maintenance of the genetic diversity in the breeding colonies and enables identification of "responders" and "non-responders", significantly contributing to a reduction of animal numbers in respective disease models and refinement of experimental outcomes (3Rs). Hence, any research project in Europe using nonhuman primate models of human infectious and autoimmune diseases will benefit from the availability of these genotyping tools. These tools will include typing of polymorphic genes and microsatellite markers from these immune regions. Additionally, this pilot study will be supplemented by the identification of a reduced set of microsatellite markers for genome-wide analysis of rhesus and cynomolgus macaques.

The newly developed tools in this research initiative can then be used for the genetic characterisation of the breeding colonies in the various primate centers to provide users with genetically characterized nonhuman primates. Additonally, the typing knowledge to be developed can be transferred to users for genetic characterization of their own colonies.