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Updated: Jan 20, 2026
Gene Editing of Primary Rhesus Macaque B Cells
Published on: February 10, 2023
Next-Generation Short-Read Sequencing Reveals Impacts on Major Histocompatibility Complex Diversity Resulting From
Sreetharan Kanthaswamy1,2, Roger W Wiseman3, Miranda R Stauss3
1California National Primate Research Center, University of California, Davis, California, USA.
Recruitment strategies significantly impact rhesus macaque (Macaca mulatta) major histocompatibility complex (MHC) diversity, leading to genetic divergence. Monitoring both MHC and short tandem repeat (STR) diversity is crucial for managing genetically engineered populations.
Area of Science:
- Immunogenetics
- Population Genetics
- Primate Models
Background:
- The Caribbean Primate Research Center (CPRC) established a specific-pathogen-free (SPF) rhesus macaque colony using founders from Cayo Santiago.
- Colony expansion involved rederivation from SPF predecessors and continued translocations from Cayo Santiago.
- Understanding the long-term immunogenetic composition of this SPF colony is vital for research applications.
Purpose of the Study:
- To analyze the longitudinal changes in major histocompatibility complex (MHC) and short tandem repeat (STR) genetic composition within the CPRC SPF rhesus macaque colony.
- To compare MHC and STR population structure across five SPF birth cohorts spanning from 1998 to 2022.
- To investigate the influence of recruitment strategies on MHC and STR diversity patterns over time.
Main Methods:
- Utilized next-generation short-read sequencing to generate an MHC database for Mamu-A, Mamu-B (Class I), and Mamu-DRB (Class II) loci.
- Compared MHC loci composition with 27 non-syntenic short tandem repeats (STRs) across five 5-year SPF birth cohorts.
- Analyzed heterozygosity (observed and expected) and pairwise differentiation (FST) to assess genetic diversity and structure.
Main Results:
- No significant relationship was found between MHC and STR heterozygosity values; STRs showed greater and more consistent heterogeneity.
- Longitudinal changes in expected MHC heterozygosity were more pronounced than those observed in STRs.
- MHC loci exhibited greater differentiation between birth cohorts compared to negligible differentiation in STRs, with divergence increasing over time due to recruitment strategies.
Conclusions:
- Recruitment strategies are the primary drivers of longitudinal MHC diversity patterns in the CPRC SPF rhesus macaque colony.
- MHC loci remain under selection even in a genetically managed population, as evidenced by divergence from uncorrelated STR variation.
- Direct MHC assessment and consideration of both MHC and STR diversity are essential for effective management decisions in primate colonies.
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