Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B

Martin, A.; Kulski, Jerzy K.; Gaudieri, Silvana; Witt, Campbell S.; Freitas, Elizabeth; Trowsdale, John; Christiansen, Frank

doi:10.1016/j.gene.2004.03.018

Cited by 113 publications

(102 citation statements)

References 35 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although the lowfrequency core haplotypes show high homozygosity as expected, core haplotypes at high frequency in the Irish population have higher than expected homozygosity at the telomeric KIR3DL2 locus despite the fact that KIR3DL2 is more polymorphic than KIR2DL3 (Figure 3d). Although lower recombination rates telomeric of the core may give rise to the trend observed, 25,26 the data may alternatively suggest positive selection acting on these cores. In support of this, the highfrequency core haplotype defined by KIR3DS1 is only ever found with KIR3DL2*007 and this combination of KIR3DL1 and KIR3DL2 alleles has previously been found together in the Mexican and Japanese populations.…”

Section: Resultsmentioning

confidence: 84%

Signatures of natural selection and coevolution between killer cell immunoglobulin-like receptors (KIR) and HLA class I genes

et al. 2010

View full text Add to dashboard Cite

Natural killer (NK) cells are lymphocytes of the innate immune system. In humans, NK cell activities are partly controlled by the diverse killer immunoglobulin-like receptor (KIR) gene family. The importance of NK cells in both immunity to infection and reproduction makes KIR strong candidates for genes undergoing dynamic evolution in the human genome. Using highresolution allelic typing, we investigated the potential role of natural selection in the diversification of KIR in the Irish population. Higher diversity than expected is observed at several loci, consistent with a history of balancing selection acting to maintain several allelic variants at high frequency in the population. KIR diversity is enhanced further at the haplotype level with functional polymorphisms at KIR2DL4, KIR3DL1 and KIR2DS4 defining nine 'core' haplotypes. Analysis of these core haplotypes in combination with human leukocyte antigen (HLA) class I ligands revealed several nonrandom associations. In particular, the KIR:HLA association for the core haplotype defined by KIR3DL1*01502 was female specific and a likely consequence of negative selection acting against KIR3DL1*01502 on an HLA-C1/C1 background. Many of the associations between KIR and HLA in the Irish differ from those previously reported, which argues against universal selective pressures for specific KIR:HLA combinations in diverse human populations.

show abstract

Section: Resultsmentioning

confidence: 84%

Signatures of natural selection and coevolution between killer cell immunoglobulin-like receptors (KIR) and HLA class I genes

et al. 2010

View full text Add to dashboard Cite

show abstract

“…This cellular regulation can influence the course of infections, autoimmunity, cancers and other diseases. [1][2][3][4][5] The KIR cluster contains 15 genes and 2 pseudogenes, 6 which are segregated within the centromeric and telomeric portions of the cluster. The centromeric and telomeric regions are flanked by framework genes KIR3DL3 and KIR3DL2, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Haplotype A is defined by the presence of either KIR2DL3 or KIR2DL1 in the centromeric portion and KIR3DL1 or KIR2DS4 in the telomeric region. 6 In contrast, the B haplotype is defined by KIR2DS2 or KIR2DL2 in the centromeric region and KIR3DS1, KIR2DL5A, KIR2DL5B, KIR2DS5 or KIR2DS1 in the telomeric segment. Centromeric and telomeric influences can also provide another level of complexity.…”

Section: Introductionmentioning

confidence: 99%

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

et al. 2011

View full text Add to dashboard Cite

Genetic differences in immune regulators influence disease resistance and susceptibility patterns. There are major health discrepancies in immune-mediated diseases between Caucasians and Canadian Aboriginal people, as well as with other indigenous people of the Americas. Environmental factors offer a limited explanation as Aboriginal people also demonstrate a rare resistance to chronic hepatitis C virus infection. Killer immunoglobulin-like receptors (KIRs) are known modulators of viral responses and autoimmune diseases. The possibility that variation in KIR cluster profiles contribute to the health outcomes of Aboriginal people was evaluated with Canadian Caucasian (n¼93, population controls) and Aboriginal (n¼86) individuals. Relative to Caucasians, the Aboriginal KIR cluster displayed a greater immune activating phenotype associated with genes of the B haplotype situated within the telomeric region. In conjunction, there was a decrease in the genes of the B haplotype from the centromeric region. Caucasian and Aboriginal cohorts further demonstrated distinct genotype and haplotype relationships enforcing the disconnect between the B haplotype centromeric and telomeric regions within the Aboriginal population. Moreover, Caucasian KIR cluster patterns reflected studies of Caucasians globally, as well as Asians. In contrast, the unique pattern of the Canadian Aboriginal cohort mirrored the phenotype of other indigenous peoples of the Americas, but not that of Caucasians or Asians. Taken together, these data suggest that historically indigenous peoples of the Americas were subject to immune selection processes that could be influencing the current disease resistance and susceptibility patterns of their descendents.

show abstract

“…KIR receptors are encoded by a family of tightly clustered genes on leukocyte receptor complex at chromosome 19q13.4. 41 The number and type of KIR genes vary substantially between haplotypes 41,42 and display sequence polymorphism. 43,44 Patterns of linkage disequilibrium divide the KIR haplotype between 3DP1 and 2DL4 into two halves.…”

Section: Introductionmentioning

confidence: 99%

Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals

Levinson

Luo

et al. 2008

Genes Immun

View full text Add to dashboard Cite

Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B

Cited by 113 publications

References 35 publications

Signatures of natural selection and coevolution between killer cell immunoglobulin-like receptors (KIR) and HLA class I genes

Signatures of natural selection and coevolution between killer cell immunoglobulin-like receptors (KIR) and HLA class I genes

The potential influence of KIR cluster profiles on disease patterns of Canadian Aboriginals and other indigenous peoples of the Americas

Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals

Contact Info

Product

Resources

About