Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description

Immunogenetics. 2016 Jul;68(6-7):417-428. doi: 10.1007/s00251-016-0921-2. Epub 2016 May 27.

Abstract

Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

Keywords: Cynomolgus macaque; Diversity genes; Joining genes; Macaca fascicularis; V-D-J rearrangement; Variable genes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromatography, Liquid
  • Genes, Immunoglobulin Heavy Chain / genetics*
  • Genes, Immunoglobulin Heavy Chain / immunology
  • Genome
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin Variable Region / immunology
  • Immunoglobulin Variable Region / metabolism
  • Macaca fascicularis / genetics*
  • Macaca fascicularis / immunology
  • Molecular Sequence Annotation
  • Phylogeny
  • Proteomics
  • Species Specificity
  • Tandem Mass Spectrometry

Substances

  • Immunoglobulin Variable Region