Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The mosaic of KIR haplotypes in rhesus macaques.

ABSTRACT: To further refine and improve biomedical research in rhesus macaques, it is necessary to increase our knowledge concerning both the degree of allelic variation (polymorphism) and diversity (gene copy number variation) in the killer cell immunoglobulin-like receptor (KIR) gene cluster. Pedigreed animals in particular should be studied, as segregation data will provide clues to the linkage of particular KIR genes/alleles segregating on a haplotype and to its gene content as well. A dual strategy allowed us to screen the presence and absence of genes and the corresponding transcripts, as well as to track differences in transcription levels. On the basis of this approach, 14 diverse KIR haplotypes have been described. These haplotypes consist of multiple inhibitory and activating Mamu-KIR genes, and any gene present on one haplotype may be absent on another. This suggests that the cost of accelerated evolution by recombination may be the loss of certain framework genes on a haplotype.

SUBMITTER: Blokhuis JH

PROVIDER: S-EPMC2858804 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The mosaic of KIR haplotypes in rhesus macaques.

Blokhuis Jeroen H JH van der Wiel Marit K MK Doxiadis Gaby G M GG Bontrop Ronald E RE

Immunogenetics 20100305 5

To further refine and improve biomedical research in rhesus macaques, it is necessary to increase our knowledge concerning both the degree of allelic variation (polymorphism) and diversity (gene copy number variation) in the killer cell immunoglobulin-like receptor (KIR) gene cluster. Pedigreed animals in particular should be studied, as segregation data will provide clues to the linkage of particular KIR genes/alleles segregating on a haplotype and to its gene content as well. A dual strategy a ...[more]

PMID: 20204612

Similar Datasets

Complete human and rhesus macaque Kir haplotypes

Project description:Using Cas9 enrichment and Nanopore sequencing, complete KIR haplotypes were characterized in humans and rhesus macaques.

| PRJEB43311 | ENA

Multiple KIR gene polymorphisms are associated with plasma viral loads in SIV-infected rhesus macaques.

Project description:Innate immune mechanisms play a deterministic role in the rate of disease progression during acute infection in HIV infected humans and SIV infection of non-human primates. The role NK cells play in mediating such an effect has thus gained importance. One of the major sets of molecules that regulate NK cell function are the killer cell immunoglobulin-like molecules (KIR's). Our laboratory has previously shown an association of KIR3DL alleles 13 and 14 with high plasma viral loads in a cohort of SIV-infected rhesus macaques. To gain a more detailed understanding of the role of KIR polymorphisms, our laboratory herein conducted studies of three additional KIR loci and show that select KIR3DH alleles appear to be more strongly associated with high plasma viral loads than KIR3DL alleles 13 and 14. In addition, we herein document the existence of additional new alleles for the KIR1D, KIR2DL4, and the KIR3DH loci.

| S-EPMC2883653 | biostudies-literature

Complete characterization of killer Ig-like receptor (KIR) haplotypes in Mauritian cynomolgus macaques: novel insights into nonhuman primate KIR gene content and organization.

Project description:Killer Ig-like receptors (KIRs) are implicated in protection from multiple pathogens including HIV, human papillomavirus, and malaria. Nonhuman primates such as rhesus and cynomolgus macaques are important models for the study of human pathogens; however, KIR genetics in nonhuman primates are poorly defined. Understanding KIR allelic diversity and genomic organization are essential prerequisites to evaluate NK cell responses in macaques. In this study, we present a complete characterization of KIRs in Mauritian cynomolgus macaques, a geographically isolated population. In this study we demonstrate that only eight KIR haplotypes are present in the entire population and characterize the gene content of each. Using the simplified genetics of this population, we construct a model for macaque KIR genomic organization, defining four putative KIR3DL loci, one KIR3DH, two KIR2DL, and one KIR1D. We further demonstrate that loci defined in Mauritian cynomolgus macaques can be applied to rhesus macaques. The findings from this study fundamentally advance our understanding of KIR genetics in nonhuman primates and establish a foundation from which to study KIR signaling in disease pathogenesis.

| S-EPMC2832209 | biostudies-literature

Short KIR haplotypes in pygmy chimpanzee (Bonobo) resemble the conserved framework of diverse human KIR haplotypes.

Project description:Some pygmy chimpanzees (also called Bonobos) give much simpler patterns of hybridization on Southern blotting with killer cell immunoglobulin-like receptor (KIR) cDNA probes than do either humans or common chimpanzees. Characterization of KIRs from pygmy chimpanzees having simple and complex banding patterns identified nine different KIRs, representing seven genes. Five of these genes have orthologs in the common chimpanzee, and three of them (KIRCI, KIR2DL4, and KIR2DL5) also have human orthologs. The remaining two genes are KIR3D paralogous to the human and common chimpanzee major histocompatibility complex A- and/or -B-specific KIRs. Within a pygmy chimpanzee family, KIR haplotypes were defined. Simple patterns on Southern blot were due to inheritance of "short" KIR haplotypes containing only three KIR genes, KIRCI, KIR2DL4, and KIR3D, each of which represents one of the three major KIR lineages. These three genes in pygmy chimpanzees or their corresponding genes in humans and common chimpanzees form the conserved "framework" common to all KIR haplotypes in these species and upon which haplotypic diversity is built. The fecundity and health of individual pygmy chimpanzees who are homozygotes for short KIR haplotypes attest to the viability of short KIR haplotypes, indicating that they can provide minimal, essential KIRs for the natural killer and T cells of the hominoid immune system.

| S-EPMC2195888 | biostudies-literature

Co-evolution of the MHC class I and KIR gene families in rhesus macaques: ancestry and plasticity.

Project description:Researchers dealing with the human leukocyte antigen (HLA) class I and killer immunoglobulin receptor (KIR) multi-gene families in humans are often wary of the complex and seemingly different situation that is encountered regarding these gene families in Old World monkeys. For the sake of comparison, the well-defined and thoroughly studied situation in humans has been taken as a reference. In macaques, both the major histocompatibility complex class I and KIR gene families are plastic entities that have experienced various rounds of expansion, contraction, and subsequent recombination processes. As a consequence, haplotypes in macaques display substantial diversity with regard to gene copy number variation. Additionally, for both multi-gene families, differential levels of polymorphism (allelic variation), and expression are observed as well. A comparative genetic approach has allowed us to answer questions related to ancestry, to shed light on unique adaptations of the species' immune system, and to provide insights into the genetic events and selective pressures that have shaped the range of these gene families.

| S-EPMC4544828 | biostudies-literature

Human and rhesus macaque KIR haplotypes defined by its transcriptome

Project description:Human and rhesus macaque KIR haplotypes defined by its transcriptome.

| PRJEB22235 | ENA

The KIR gene transcriptomes of rhesus and cynomolgus macaques

Project description:The KIR gene transcriptomes of rhesus and cynomolgus macaques

| PRJEB33481 | ENA

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

Project description:The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses.

| S-EPMC5542451 | biostudies-literature

KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques.

Project description:Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues. NK cell responses in blood were broadly stimulated, as indicated by rapid increases in the CD16+ population during acute infection and sustained increases in the CD16+ and CD16-CD56- populations during chronic infection. Markers of proliferation (Ki-67), activation (CD69 & HLA-DR) and antiviral activity (CD107a & TNF?) were also widely expressed, but began to diverge during chronic infection, as reflected by sustained CD107a and TNF? upregulation by KIR3DL01+, but not by KIR3DL05+ NK cells. Significant increases in the frequency of KIR3DL01+ (but not KIR3DL05+) NK cells were also observed in tissues, particularly in the gut-associated lymphoid tissues, where this receptor was preferentially upregulated on CD56+ and CD16-CD56- subsets. These results reveal broad NK cell activation and dynamic changes in the phenotypic properties of NK cells in response to SIV infection, including the enrichment of KIR3DL01+ NK cells in tissues that support high levels of virus replication.

| S-EPMC5529027 | biostudies-literature

Efficient Sequencing, Assembly, and Annotation of Human KIR Haplotypes.

Project description:The homology, recombination, variation, and repetitive elements in the natural killer-cell immunoglobulin-like receptor (KIR) region has made full haplotype DNA interpretation impossible in a high-throughput workflow. Here, we present a new approach using long-read sequencing to efficiently capture, sequence, and assemble diploid human KIR haplotypes. Probes were designed to capture KIR fragments efficiently by leveraging the repeating homology of the region. IDT xGen® Lockdown probes were used to capture 2-8 kb of sheared DNA fragments followed by sequencing on a PacBio Sequel. The sequences were error corrected, binned, and then assembled using the Canu assembler. The location of genes and their exon/intron boundaries are included in the workflow. The assembly and annotation was evaluated on 16 individuals (8 African American and 8 Europeans) from whom ground truth was known via long-range sequencing with fosmid library preparation. Using only 18 capture probes, the results show that the assemblies cover 97% of the GenBank reference, are 99.97% concordant, and it takes only 1.8 haplotigs to cover 75% of the reference. We also report the first assembly of diploid KIR haplotypes from long-read WGS. Our targeted hybridization probe capture and sequencing approach is the first of its kind to fully sequence and phase all diploid human KIR haplotypes, and it is efficient enough for population-scale studies and clinical use. The open and free software is available at https://github.com/droeatumn/kass and supported by a environment at https://hub.docker.com/repository/docker/droeatumn/kass.

| S-EPMC7581912 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data