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MHC genotyping from rhesus macaque exome sequences

By John R. Caskey, Roger W. Wiseman, Julie A. Karl, David A. Baker, Taylor Lee, Muthuswamy Raveendran, R. Alan Harris, Jianhong Hu, Donna Muzny, Jeffrey Rogers, David H O'Connor

Posted 02 May 2019
bioRxiv DOI: 10.1101/625244 (published DOI: 10.1007/s00251-019-01125-w)

Indian rhesus macaque major histocompatibility complex (MHC) variation can influence the outcomes of transplantation and infectious disease studies. Frequently, rhesus macaques are MHC genotyped to identify variants that could account for unexpected results. Since the MHC is only one region in the genome where variation could impact experimental outcomes, strategies for simultaneously profiling variation in the macaque MHC and the remainder of the protein coding genome would be useful. Here we introduce macaque exome sequence (MES) genotyping, in which MHC class I and class II genotypes are determined with high confidence using target-enrichment probes that are enriched for MHC sequences. For a cohort of 27 Indian rhesus macaques, we describe two methods for obtaining MHC genotypes from MES data and demonstrate that the MHC class I and class II genotyping results obtained with these methods are 98.1% and 98.7% concordant, respectively, with expected MHC genotypes. In contrast, conventional MHC genotyping results obtained by deep sequencing of short multiplex PCR amplicons were only 92.6% concordant with expectations for this cohort.

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