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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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Comparison of the linkage disequilibrium observed in the KIR region between the Ugandan population and six African and seven European populations. The LD values calculated for 11 KIR gene loci for Ugandan population are compared with the values obtained using the same method by Single et al. (2008). Red represents strong positive LD, blue represents strong negative LD
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Fig6: Comparison of the linkage disequilibrium observed in the KIR region between the Ugandan population and six African and seven European populations. The LD values calculated for 11 KIR gene loci for Ugandan population are compared with the values obtained using the same method by Single et al. (2008). Red represents strong positive LD, blue represents strong negative LD

Mentions: The LD between KIR genes was calculated for the 12 KIR loci in order to observe the pairwise association of genes in this population (Table 3). The strongest positive and negative LD values were observed between KIR2DL1 and KIR2DP1 (0.88) and KIR2DL2 and KIR2DL3 (−0.35), consistent with a previous report for six African populations (Single et al. 2008). A graphical analysis of Ugandan compared to these African populations and seven European populations is shown (Fig. 6). The positive LD between KIR2DS1, KIR2DS5, and KIR3DS1 observed in Europeans is absent in Africans; in contrast, a positive association is seen between KIR2DS5 and KIR2DS2-KIR2DL2, consistent with the location of KIR2DS5 gene in the centromeric B region where KIR2DS3 is generally located in Europeans. Overall, the LD values observed for the KIR genes are less extreme in Africa.Table 3


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)

Comparison of the linkage disequilibrium observed in the KIR region between the Ugandan population and six African and seven European populations. The LD values calculated for 11 KIR gene loci for Ugandan population are compared with the values obtained using the same method by Single et al. (2008). Red represents strong positive LD, blue represents strong negative LD
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824577&req=5

Fig6: Comparison of the linkage disequilibrium observed in the KIR region between the Ugandan population and six African and seven European populations. The LD values calculated for 11 KIR gene loci for Ugandan population are compared with the values obtained using the same method by Single et al. (2008). Red represents strong positive LD, blue represents strong negative LD
Mentions: The LD between KIR genes was calculated for the 12 KIR loci in order to observe the pairwise association of genes in this population (Table 3). The strongest positive and negative LD values were observed between KIR2DL1 and KIR2DP1 (0.88) and KIR2DL2 and KIR2DL3 (−0.35), consistent with a previous report for six African populations (Single et al. 2008). A graphical analysis of Ugandan compared to these African populations and seven European populations is shown (Fig. 6). The positive LD between KIR2DS1, KIR2DS5, and KIR3DS1 observed in Europeans is absent in Africans; in contrast, a positive association is seen between KIR2DS5 and KIR2DS2-KIR2DL2, consistent with the location of KIR2DS5 gene in the centromeric B region where KIR2DS3 is generally located in Europeans. Overall, the LD values observed for the KIR genes are less extreme in Africa.Table 3

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