MHC genotyping from rhesus macaque exome sequences.

Area of Science:

• Genomics
• Immunogenetics
• Primate research

Background:

• Variation in the Indian rhesus macaque major histocompatibility complex (MHC) significantly impacts transplantation and infectious disease study outcomes.
• Accurate MHC genotyping is essential for interpreting experimental results in rhesus macaque models.
• Current genotyping methods may not capture the full scope of genomic variation influencing experimental outcomes.

Purpose of the Study:

• To develop and validate a novel method for simultaneously profiling variation in the macaque MHC and the broader protein-coding genome.
• To assess the accuracy of macaque exome sequence (MES) genotyping for MHC class I and II profiling.
• To compare the concordance of MES genotyping with conventional MHC genotyping methods.

Main Methods:

• Developed macaque exome sequence (MES) genotyping using target-capture probes enriched for MHC sequences.
• Applied two distinct analytical methods to derive MHC genotypes from MES data.
• Compared MES genotyping results with expected MHC genotypes and conventional deep sequencing methods in a cohort of 27 Indian rhesus macaques.

Main Results:

• MES genotyping achieved high concordance with expected MHC genotypes: 98.1% for MHC class I and 98.7% for MHC class II.
• Conventional MHC genotyping methods showed lower concordance (92.6%) with expected genotypes in the same cohort.
• The MES genotyping approach demonstrated superior accuracy and reliability for MHC profiling.

Conclusions:

• Macaque exome sequence (MES) genotyping provides a more accurate and comprehensive approach for profiling MHC variation in Indian rhesus macaques.
• This method facilitates simultaneous assessment of MHC and other genomic variations, enhancing the interpretability of experimental outcomes.
• MES genotyping represents a significant advancement for genetic studies utilizing rhesus macaque models.