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Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population.

Nakimuli A, Chazara O, Farrell L, Hiby SE, Tukwasibwe S, Knee O, Jayaraman J, Traherne JA, Elliott AM, Kaleebu P, Mirembe F, Moffett A - Immunogenetics (2013)

Bottom Line: We studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort (n = 492) from Kampala, Uganda, East Africa and compared our findings with published data from other populations in sub-Saharan Africa (SSA) and several European populations.C1 and C2 frequencies were similar to other SSA populations with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average 39.7 %).Our results will help understand how KIR/HLA-C interactions contribute to resistance to pathogens and reproductive success.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Makerere University, Kampala, Uganda.

ABSTRACT
Killer cell immunoglobulin-like receptor (KIR) genes are expressed by natural killer cells and encoded by a family of genes exhibiting considerable haplotypic and allelic variation. HLA-C molecules, the dominant ligands for KIR, are present in all individuals and are discriminated by two KIR epitopes, C1 and C2. We studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort (n = 492) from Kampala, Uganda, East Africa and compared our findings with published data from other populations in sub-Saharan Africa (SSA) and several European populations. We find considerably more KIR diversity and weaker linkage disequilibrium in SSA compared to the European populations and describe several novel KIR genotypes. C1 and C2 frequencies were similar to other SSA populations with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average 39.7 %). Analysis of this large cohort from Uganda in the context of other African populations reveals variations in KIR and HLA-C1 and C2 that are consistent with migrations within Africa and potential selection pressures on these genes. Our results will help understand how KIR/HLA-C interactions contribute to resistance to pathogens and reproductive success.

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Inferred KIR haplotypes for 15 individuals representing 13 KIR genotypes. Genes are presented in the order observed on published sequenced KIR haplotypes. Inhibitory genes are in red, activating genes are in blue, and pseudo genes are in gray. Haplotype names are according to Pyo et al. (2013)
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Fig4: Inferred KIR haplotypes for 15 individuals representing 13 KIR genotypes. Genes are presented in the order observed on published sequenced KIR haplotypes. Inhibitory genes are in red, activating genes are in blue, and pseudo genes are in gray. Haplotype names are according to Pyo et al. (2013)

Mentions: The remaining 33 genotypes are rare (<1 %), comprising 9.9 % of the total population. These represent unusual genotypes, including contracted or extended KIR haplotypes containing an unusual combination of KIR genes. In order to investigate these haplotypes, which arise from ancestral unequal recombination events, 15 individuals were fully typed for KIR gene copy number. Firstly, different regions of KIR3DL1 (exons 4 and 9) and of KIR3DL2 (exons 4 and 9) were separately typed for copy number to detect the KIR3DL1/3DL2 hybrid gene (Shilling et al. 2002). Nine out of 15 individuals had one or two copies of this telomeric region (tA01-hybd1; individuals 1–6 and 13–15, Fig. 4). Two additional genotypes (numbers 438 and 252/72/83, Fig. 3) have KIR3DL1 present without KIR2DS4, and these individuals are also likely to have the same contracted telomeric region (tA01-hybd1). This contracted haplotype was observed in this Ugandan cohort at an underestimated frequency of 1.7 %, which is lower than the 6.5 % from other African populations (Norman et al. 2009; Norman et al. 2007), because the common telomeric A region (tA01) will hide this deletion, as seen with individual 6. Secondly, nine different individuals (individuals 7–15) have one or two copies of other contracted haplotypes defined by a deletion of the central framework genes, KIR3DP1, KIR2DL4, and KIR3DS1, defined as del6 (Pyo et al. 2010) and previously reported in individuals of African ancestry (Gómez-Lozano et al. 2003; Norman et al. 2002). Using these individuals and the similar KIR genotypes with KIR2DS1 present without KIR3DS1, the frequency of this deletion in Uganda is greater than 7.25 %.Fig. 4


Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a Ugandan population.

Nakimuli A, Chazara O, Farrell L, Hiby SE, Tukwasibwe S, Knee O, Jayaraman J, Traherne JA, Elliott AM, Kaleebu P, Mirembe F, Moffett A - Immunogenetics (2013)

Inferred KIR haplotypes for 15 individuals representing 13 KIR genotypes. Genes are presented in the order observed on published sequenced KIR haplotypes. Inhibitory genes are in red, activating genes are in blue, and pseudo genes are in gray. Haplotype names are according to Pyo et al. (2013)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig4: Inferred KIR haplotypes for 15 individuals representing 13 KIR genotypes. Genes are presented in the order observed on published sequenced KIR haplotypes. Inhibitory genes are in red, activating genes are in blue, and pseudo genes are in gray. Haplotype names are according to Pyo et al. (2013)
Mentions: The remaining 33 genotypes are rare (<1 %), comprising 9.9 % of the total population. These represent unusual genotypes, including contracted or extended KIR haplotypes containing an unusual combination of KIR genes. In order to investigate these haplotypes, which arise from ancestral unequal recombination events, 15 individuals were fully typed for KIR gene copy number. Firstly, different regions of KIR3DL1 (exons 4 and 9) and of KIR3DL2 (exons 4 and 9) were separately typed for copy number to detect the KIR3DL1/3DL2 hybrid gene (Shilling et al. 2002). Nine out of 15 individuals had one or two copies of this telomeric region (tA01-hybd1; individuals 1–6 and 13–15, Fig. 4). Two additional genotypes (numbers 438 and 252/72/83, Fig. 3) have KIR3DL1 present without KIR2DS4, and these individuals are also likely to have the same contracted telomeric region (tA01-hybd1). This contracted haplotype was observed in this Ugandan cohort at an underestimated frequency of 1.7 %, which is lower than the 6.5 % from other African populations (Norman et al. 2009; Norman et al. 2007), because the common telomeric A region (tA01) will hide this deletion, as seen with individual 6. Secondly, nine different individuals (individuals 7–15) have one or two copies of other contracted haplotypes defined by a deletion of the central framework genes, KIR3DP1, KIR2DL4, and KIR3DS1, defined as del6 (Pyo et al. 2010) and previously reported in individuals of African ancestry (Gómez-Lozano et al. 2003; Norman et al. 2002). Using these individuals and the similar KIR genotypes with KIR2DS1 present without KIR3DS1, the frequency of this deletion in Uganda is greater than 7.25 %.Fig. 4

Bottom Line: We studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort (n = 492) from Kampala, Uganda, East Africa and compared our findings with published data from other populations in sub-Saharan Africa (SSA) and several European populations.C1 and C2 frequencies were similar to other SSA populations with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average 39.7 %).Our results will help understand how KIR/HLA-C interactions contribute to resistance to pathogens and reproductive success.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Makerere University, Kampala, Uganda.

ABSTRACT
Killer cell immunoglobulin-like receptor (KIR) genes are expressed by natural killer cells and encoded by a family of genes exhibiting considerable haplotypic and allelic variation. HLA-C molecules, the dominant ligands for KIR, are present in all individuals and are discriminated by two KIR epitopes, C1 and C2. We studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort (n = 492) from Kampala, Uganda, East Africa and compared our findings with published data from other populations in sub-Saharan Africa (SSA) and several European populations. We find considerably more KIR diversity and weaker linkage disequilibrium in SSA compared to the European populations and describe several novel KIR genotypes. C1 and C2 frequencies were similar to other SSA populations with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average 39.7 %). Analysis of this large cohort from Uganda in the context of other African populations reveals variations in KIR and HLA-C1 and C2 that are consistent with migrations within Africa and potential selection pressures on these genes. Our results will help understand how KIR/HLA-C interactions contribute to resistance to pathogens and reproductive success.

Show MeSH
Related in: MedlinePlus