Abstract
Rhesus macaque is one of the most widely used primate model animals for immunological research of infectious diseases including human immunodeficiency virus (HIV) infection. It is well known that major histocompatibility complex (MHC) class I genotypes affect the susceptibility and disease progression to simian immunodeficiency virus (SIV) in rhesus macaques, which is resembling to HIV in humans. It is required to convincingly determine the MHC genotypes in the immunological investigations, that is why several next-generation sequencing (NGS)-based methods have been established. In general, NGS-based genotyping methods using short amplicons are not often applied to MHC because of increasing number of alleles and inevitable ambiguity in allele detection, although there is an advantage of short read sequencing systems that are commonly used today. In this study, we developed a new high-throughput NGS-based genotyping method for MHC class I alleles in rhesus macaques and cynomolgus macaques. By using our method, 95% and 100% of alleles identified by PCR cloning-based method were detected in rhesus macaques and cynomolgus macaques, respectively, which were highly correlated with their expression levels. It was noted that the simulation of new-allele detection step using artificial alleles differing by a few nucleotide sequences from a known allele could be identified with high accuracy and that we could detect a real novel allele from a rhesus macaque sample. These findings supported that our method could be adapted for primate animal models such as macaques to reduce the cost and labor of previous NGS-based MHC genotyping.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The sequence read data (FASTQ format) used in this study have been deposited in DNA Data Bank of Japan (DDBJ) under the accession number DRA008929. The scripts used in this study are available on GitHub repository under the following address: https://github.com/ktresearch/ngs_genotyping_macaque.
References
Adams EJ, Parham P (2001) Species-specific evolution of MHC class I genes in the higher primates. Immunol Rev 183:41–64
Barouch DH, Santra S, Schmitz JE, Kuroda MJ, Fu TM, Wagner W, Bilska M, Craiu A, Zheng XX, Krivulka GR, Beaudry K, Lifton MA, Nickerson CE, Trigona WL, Punt K, Freed DC, Guan L, Dubey S, Casimiro D, Simon A, Davies ME, Chastain M, Strom TB, Gelman RS, Montefiori DC, Lewis MG, Emini EA, Shiver JW, Letvin NL (2000) Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290:486–492
Boyson JE, Shufflebotham C, Cadavid LF, Urvater JA, Knapp LA, Hughes AL, Watkins DI (1996) The MHC class I genes of the rhesus monkey. Different evolutionary histories of MHC class I and II genes in primates. J Immunol 156:4656–4665
Budde ML, Lhost JJ, Burwitz BJ, Becker EA, Burns CM, O’Connor SL, Karl JA, Wiseman RW, Bimber BN, Zhang GL, Hildebrand W, Brusic V, O’Connor DH (2011) Transcriptionally abundant major histocompatibility complex class I alleles are fundamental to nonhuman primate simian immunodeficiency virus-specific CD8+ T cell responses. J Virol 85:3250–3261
Caboche S, Audebert C, Lemoine Y, Hot D (2014) Comparison of mapping algorithms used in high-throughput sequencing: application to Ion Torrent data. BMC Genomics 15:264
Caskey JR, Wiseman RW, Karl JA, Baker DA, Lee T, Maddox RJ, Raveendran M, Harris RA, Hu J, Muzny DM, Rogers J, O’Connor DH (2019) MHC genotyping from rhesus macaque exome sequences. Immunogenetics 71:531–544
Daza-Vamenta R, Glusman G, Rowen L, Guthrie B, Geraghty DE (2004) Genetic divergence of the rhesus macaque major histocompatibility complex. Genome Res 14:1501–1515
Dudley DM, Karl JA, Creager HM, Bohn PS, Wiseman RW, O’Connor DH (2014) Full-length novel MHC class I allele discovery by next-generation sequencing: two platforms are better than one. Immunogenetics 66:15–24
Fernandez CS, Reece JC, Saepuloh U, De Rose R, Ishkandriati D, O’Connor DH, Wiseman RW, Kent SJ (2011) Screening and confirmatory testing of MHC class I alleles in pig-tailed macaques. Immunogenetics 63:511–521
Goodwin S, McPherson JD, McCombie WR (2016) Coming of age: ten years of next-generation sequencing technologies. Nat Rev Genet 17:333–351
Hirotsu Y, Kojima Y, Okimoto K, Amemiya K, Mochizuki H, Omata M (2016) Comparison between two amplicon-based sequencing panels of different scales in the detection of somatic mutations associated with gastric cancer. BMC Genomics 17:833
Karl JA, Bohn PS, Wiseman RW, Nimityongskul FA, Lank SM, Starrett GJ, O’Connor DH (2013) Major histocompatibility complex class I haplotype diversity in Chinese rhesus macaques. G3 (Bethesda) 3:1195–1201
Karl JA, Graham ME, Wiseman RW, Heimbruch KE, Gieger SM, Doxiadis GG, Bontrop RE, O’Connor DH (2017) Major histocompatibility complex haplotyping and long-amplicon allele discovery in cynomolgus macaques from Chinese breeding facilities. Immunogenetics 69:211–229
Karl JA, Heimbruch KE, Vriezen CE, Mironczuk CJ, Dudley DM, Wiseman RW, O’Connor DH (2014) Survey of major histocompatibility complex class II diversity in pig-tailed macaques. Immunogenetics 66:613–623
Kulski JK, Anzai T, Shiina T, Inoko H (2004) Rhesus macaque class I duplicon structures, organization, and evolution within the alpha block of the major histocompatibility complex. Mol Biol Evol 21:2079–2091
Loffredo JT, Bean AT, Beal DR, León EJ, May GE, Piaskowski SM, Furlott JR, Reed J, Musani SK, Rakasz EG, Friedrich TC, Wilson NA, Allison DB, Watkins DI (2008) Patterns of CD8+ immunodominance may influence the ability of Mamu-B*08-positive macaques to naturally control simian immunodeficiency virus SIVmac239 replication. J Virol 82:1723–1738
Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads.
Mothé BR, Weinfurter J, Wang C, Rehrauer W, Wilson N, Allen TM, Allison DB, Watkins DI (2003) Expression of the major histocompatibility complex class I molecule Mamu-A*01 is associated with control of simian immunodeficiency virus SIVmac239 replication. J Virol 77:2736–2740
Naruse TK, Chen Z, Yanagida R, Yamashita T, Saito Y, Mori K, Akari H, Yasutomi Y, Miyazawa M, Matano T, Kimura A (2010) Diversity of MHC class I genes in Burmese-origin rhesus macaques. Immunogenetics 62:601–611
Nicolussi A, Belardinilli F, Mahdavian Y, Colicchia V, D’Inzeo S, Petroni M, Zani M, Ferraro S, Valentini V, Ottini L, Giannini G, Capalbo C, Coppa A (2019) Next-generation sequencing of BRCA1 and BRCA2 genes for rapid detection of germline mutations in hereditary breast/ovarian cancer. Peer J 7:e6661
Nomura T, Matano T (2012) Association of MHC-I genotypes with disease progression in HIV/SIV infections. Front Microbiol 3:234
O’Leary CE, Wiseman RW, Karl JA, Bimber BN, Lank SM, Tuscher JJ, O’Connor DH (2009) Identification of novel MHC class I sequences in pig-tailed macaques by amplicon pyrosequencing and full-length cDNA cloning and sequencing. Immunogenetics 61:689–701
Otting N, Heijmans CM, Noort RC, de Groot NG, Doxiadis GG, van Rood JJ, Watkins DI, Bontrop RE (2005) Unparalleled complexity of the MHC class I region in rhesus macaques. Proc Natl Acad Sci USA 102:1626–1631
Reynolds MR, Weiler AM, Weisgrau KL, Piaskowski SM, Furlott JR, Weinfurter JT, Kaizu M, Soma T, León EJ, MacNair C, Leaman DP, Zwick MB, Gostick E, Musani SK, Price DA, Friedrich TC, Rakasz EG, Wilson NA, McDermott AB, Boyle R, Allison DB, Burton DR, Koff WC, Watkins DI (2008) Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. J Exp Med 205:2537–2550
Saito Y, Naruse TK, Akari H, Matano T, Kimura A (2012) Diversity of MHC class I haplotypes in cynomolgus macaques. Immunogenetics 64:131–141
Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857–860
Semler MR, Wiseman RW, Karl JA, Graham ME, Gieger SM, O’Connor DH (2018) Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques. Immunogenetics 70:381–399
Shiina T, Blancher A, Inoko H, Kulski JK (2017) Comparative genomics of the human, macaque and mouse major histocompatibility complex. Immunology 150:127–138
Shiina T, Yamada Y, Aarnink A, Suzuki S, Masuya A, Ito S, Ido D, Yamanaka H, Iwatani C, Tsuchiya H, Ishigaki H, Itoh Y, Ogasawara K, Kulski JK, Blancher A (2015) Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism. Immunogenetics 67:563–578
Westbrook CJ, Karl JA, Wiseman RW, Mate S, Koroleva G, Garcia K, Sanchez-Lockhart M, O’Connor DH, Palacios G (2015) No assembly required: full-length MHC class I allele discovery by PacBio circular consensus sequencing. Hum Immunol 76:891–896
Wiseman RW, Karl JA, Bimber BN, O’Leary CE, Lank SM, Tuscher JJ, Detmer AM, Bouffard P, Levenkova N, Turcotte CL, Szekeres E, Wright C, Harkins T, O’Connor DH (2009) Major histocompatibility complex genotyping with massively parallel pyrosequencing. Nat Med 15:1322–1326
Wiseman RW, Karl JA, Bohn PS, Nimityongskul FA, Starrett GJ, O’Connor DH (2013) Haplessly hoping: macaque major histocompatibility complex made easy. ILAR J 54:196–210
Yant LJ, Friedrich TC, Johnson RC, May GE, Maness NJ, Enz AM, Lifson JD, O’Connor DH, Carrington M, Watkins DI (2006) The high-frequency major histocompatibility complex class I allele Mamu-B*17 is associated with control of simian immunodeficiency virus SIVmac239 replication. J Virol 80:5074–5077
Yasutomi Y, Reimann KA, Lord CI, Miller MD, Letvin NL (1993) Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. J Virol 67:1707–1711
Acknowledgments
We thank Ms. Misako Sato and Ms. Kazumi Hashino for their technical assistances.
Funding
This work was supported in part by research grants from the Japan Agency for Medical Research and Development (AMED), grant no. JP17fk0410203h0302 and JP18fk04100013), and a program of support for women researchers from the Tokyo Medical and Dental University.
Author information
Authors and Affiliations
Contributions
AK and TN designed the study. TM collected samples. TN performed the experiments and MHC genotyping by the PCR-cloning based method. KT performed bioinformatics analyses. AK, TN, and KT wrote the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
All care including blood sampling of animals were in accordance with the Guidelines for the Care and Use of Laboratory Animals published by the National Institute of Health (NIH Publication 85-23, revised 1985). All the procedures including use of the animal samples were subjected to prior approval by local Committee for experiments using genetically modified organisms of Tokyo Medical and Dental University (No. 2013-070C2).
Competing interest
The authors declare that they have no competing interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Tanimoto, K., Naruse, T.K., Matano, T. et al. Development and evaluation of a rapid and cost-efficient NGS-based MHC class I genotyping method for macaques by using a prevalent short-read sequencer. Immunogenetics 73, 175–186 (2021). https://doi.org/10.1007/s00251-020-01199-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-020-01199-x