, Volume 69, Issue 5, pp 325–339 | Cite as

Improved full-length killer cell immunoglobulin-like receptor transcript discovery in Mauritian cynomolgus macaques

  • Trent M. Prall
  • Michael E. Graham
  • Julie A. Karl
  • Roger W. Wiseman
  • Adam J. Ericsen
  • Muthuswamy Raveendran
  • R. Alan Harris
  • Donna M. Muzny
  • Richard A. Gibbs
  • Jeffrey Rogers
  • David H. O’ConnorEmail author
Original Article


Killer cell immunoglobulin-like receptors (KIRs) modulate disease progression of pathogens including HIV, malaria, and hepatitis C. Cynomolgus and rhesus macaques are widely used as nonhuman primate models to study human pathogens, and so, considerable effort has been put into characterizing their KIR genetics. However, previous studies have relied on cDNA cloning and Sanger sequencing that lack the throughput of current sequencing platforms. In this study, we present a high throughput, full-length allele discovery method utilizing Pacific Biosciences circular consensus sequencing (CCS). We also describe a new approach to Macaque Exome Sequencing (MES) and the development of the Rhexome1.0, an adapted target capture reagent that includes macaque-specific capture probe sets. By using sequence reads generated by whole genome sequencing (WGS) and MES to inform primer design, we were able to increase the sensitivity of KIR allele discovery. We demonstrate this increased sensitivity by defining nine novel alleles within a cohort of Mauritian cynomolgus macaques (MCM), a geographically isolated population with restricted KIR genetics that was thought to be completely characterized. Finally, we describe an approach to genotyping KIRs directly from sequence reads generated using WGS/MES reads. The findings presented here expand our understanding of KIR genetics in MCM by associating new genes with all eight KIR haplotypes and demonstrating the existence of at least one KIR3DS gene associated with every haplotype.


Killer cell immunoglobulin-like receptors Mauritian cynomolgus macaques Whole Genome and Macaque Exome Sequencing PacBio long-amplicon sequencing 



This research was supported by contracts HHSN272201600007C and HHSN272201100013C from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and was conducted at a facility constructed with support from the Research Facilities Improvement Program (RR15459-01, RR20141-01).

Supplementary material

251_2017_977_MOESM1_ESM.pdf (61 kb)
Supplementary Fig. 1 Mafa-KIR3DL and Mafa -KIR3DS phylogenetic trees. Phylogenetic analysis of MCM KIR3DL and KIR3DS sequences. Both phylogenetic trees contain the human KIR3DL1*00701 allele as an outgroup (AF262973). Bootstrapping values are shown to the left of nodes. Novel sequences are highlighted in bold font. A, the tree contains KIR3DL sequences. Vertical bars denote lineages. B, the tree contains KIR3DS sequences. (PDF 61 kb).
251_2017_977_MOESM2_ESM.docx (62 kb)
Supplementary Table 1 (DOCX 62 kb).
251_2017_977_MOESM3_ESM.docx (90 kb)
Supplementary Table 2 (DOCX 89 kb).
251_2017_977_MOESM4_ESM.docx (40 kb)
Supplementary Table 3 (DOCX 40 kb).
251_2017_977_MOESM5_ESM.docx (36 kb)
Supplementary Table 4 (DOCX 35 kb).
251_2017_977_MOESM6_ESM.docx (18 kb)
Supplementary Table 5 (DOCX 17 kb).
251_2017_977_MOESM7_ESM.docx (84 kb)
Supplementary Table 6 Comparison of sequences identified by PacBio CCS versus WGS/MES. (DOCX 84 kb).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Trent M. Prall
    • 1
  • Michael E. Graham
    • 2
  • Julie A. Karl
    • 2
  • Roger W. Wiseman
    • 1
    • 2
  • Adam J. Ericsen
    • 1
  • Muthuswamy Raveendran
    • 3
  • R. Alan Harris
    • 3
  • Donna M. Muzny
    • 3
  • Richard A. Gibbs
    • 3
  • Jeffrey Rogers
    • 3
    • 4
  • David H. O’Connor
    • 1
    • 2
    Email author
  1. 1.Wisconsin National Primate Research CenterUniversity of WisconsinMadisonUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of WisconsinMadisonUSA
  3. 3.Human Genome Sequencing CenterBaylor College of MedicineHoustonUSA
  4. 4.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA

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