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Immunogenetics

, Volume 67, Issue 10, pp 563–578 | Cite as

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing

Mafa-class I polymorphism
  • Takashi Shiina
  • Yukiho Yamada
  • Alice Aarnink
  • Shingo Suzuki
  • Anri Masuya
  • Sayaka Ito
  • Daisuke Ido
  • Hisashi Yamanaka
  • Chizuru Iwatani
  • Hideaki Tsuchiya
  • Hirohito Ishigaki
  • Yasushi Itoh
  • Kazumasa Ogasawara
  • Jerzy K. Kulski
  • Antoine Blancher
Original Paper

Abstract

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (<86 %) with primate MHC class I genes, and it was also conserved in the Vietnamese and Indonesian populations. In addition, haplotype estimations revealed 17 Mafa-A, 23 Mafa-B, and 12 Mafa-E haplotypes integrated with 84 Mafa-class I haplotypes and Mafa-F alleles. Of these, the two Mafa-class I haplotypes, F/A/E/B-Hp1 and F/A/E/B-Hp2, had the highest haplotype frequencies at 10.6 and 10.2 %, respectively. This suggests that large scale genetic screening of the Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Keywords

Cynomolgus macaque Major histocompatibility complex MHC Polymorphism Haplotype Next generation sequencing NGS Sanger sequencing 

Notes

Acknowledgments

We are grateful to Dr. Atsushi Toyoda at Center for Information Biology, Comparative Genomics Laboratory, National Institute of Genetics for making sequence data and Mr. Masayuki Tanaka, Mr. Hideki Hayashi, and Mr. Tadayuki Sato at the Education and Research Support Center, Research and Development Division, Tokai University for their technical support. This work was supported by MEXT KAKENHI (no. 221S0002), JSPS KAKENHI (no. 21300155), and was partially supported by the program “Research Center Network for Realization of Regenerative Medicine” in Japan Agency for Medical Research and Development (AMED) and from Adaptable and Seamless Technology transfer Program in AMED.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

251_2015_867_MOESM1_ESM.pptx (90 kb)
ESM 1 Figure 1 An example of the haplotype estimation method for the Mafa-A haplotypes. We used the same estimation process for the Mafa-B and Mafa-E haplotypes. (PPTX 89 kb)
251_2015_867_MOESM2_ESM.pdf (169 kb)
ESM 2 Table 1 Sequence read information obtained by the Roche Genome Sequencer 454 FLX system (PDF 169 kb)
251_2015_867_MOESM3_ESM.pdf (65 kb)
ESM 3 Table 2 Nucleotide and amino acid similarities among the Mafa-E and among the Mafa-F alleles (PDF 64 kb)
251_2015_867_MOESM4_ESM.pdf (167 kb)
ESM 4 Table 3 Estimation ofMafa-Fand Mafa-A, Mafa-A and Mafa-E, and Mafa-EandMafa-Bhaplotype information obtained by the PHASE program (PDF 167 kb)
251_2015_867_MOESM5_ESM.pdf (139 kb)
ESM 5 Table 4 Estimation of Mafa-class Ihaplotype information obtained by the PHASE program (PDF 139 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Takashi Shiina
    • 1
  • Yukiho Yamada
    • 1
    • 2
  • Alice Aarnink
    • 3
  • Shingo Suzuki
    • 1
  • Anri Masuya
    • 1
  • Sayaka Ito
    • 1
  • Daisuke Ido
    • 2
  • Hisashi Yamanaka
    • 2
  • Chizuru Iwatani
    • 4
  • Hideaki Tsuchiya
    • 4
  • Hirohito Ishigaki
    • 5
  • Yasushi Itoh
    • 5
  • Kazumasa Ogasawara
    • 5
  • Jerzy K. Kulski
    • 1
    • 6
  • Antoine Blancher
    • 3
  1. 1.Department of Molecular Life Science, Division of Basic Medical Science and Molecular MedicineTokai University School of MedicineIseharaJapan
  2. 2.Ina Research Inc.InaJapan
  3. 3.Laboratoire d’Immunogénétique moléculaireUniversité Toulouse III, Faculte de Medecine Purpan, Laboratoire d’immunologieToulouseFrance
  4. 4.Research Center for Animal Life ScienceShiga University of Medical Science, School of MedicineOhtsuJapan
  5. 5.Department of PathologyShiga University of Medical ScienceOhtsuJapan
  6. 6.Centre for Forensic ScienceThe University of Western AustraliaNedlands,Australia

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