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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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Related in: MedlinePlus

Principal component analysis based on seven KIR gene carrier frequencies for the 23 African populations described in Table 2. Arrows represent the relative contribution of each KIR gene frequency to the variability along the first two axes (PC1 and PC2)
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Fig1: Principal component analysis based on seven KIR gene carrier frequencies for the 23 African populations described in Table 2. Arrows represent the relative contribution of each KIR gene frequency to the variability along the first two axes (PC1 and PC2)

Mentions: We compared these results with data from a range of African populations where frequencies for KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, and KIR3DS1 have been reported (Table 2). Of note is that the sample size was under 100 in 19 out of 22 studies. All African populations share similar characteristics compared to UK populations with lower KIR2DS1 and KIR3DS1 carrier frequencies; the highest value for KIR2DS1 was 0.28 (Congo Mbuti) and 0.23 for KIR3DS1 (Ethiopian) compared with, respectively, 0.42 and 0.44 for the UK population. The variability of these frequencies between the African populations may be visualized using principal component analysis (Fig. 1). The Ugandan population localizes to an intermediate position, between Central and West African populations and the East African populations. Therefore, in terms of KIR gene frequencies, the Ugandan population can be regarded as intermediate to these populations. The history of human migration in Africa is consistent with this observation because Uganda is an East African country known to have been populated from the Bantu migrations from West and Central Africa (Campbell and Tishkoff 2008). Furthermore, it is in both the northern and southern hemispheres, being situated on the equatorial line.Table 2


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)

Principal component analysis based on seven KIR gene carrier frequencies for the 23 African populations described in Table 2. Arrows represent the relative contribution of each KIR gene frequency to the variability along the first two axes (PC1 and PC2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Principal component analysis based on seven KIR gene carrier frequencies for the 23 African populations described in Table 2. Arrows represent the relative contribution of each KIR gene frequency to the variability along the first two axes (PC1 and PC2)
Mentions: We compared these results with data from a range of African populations where frequencies for KIR2DL1, KIR2DL2, KIR2DL3, KIR3DL1, and KIR3DS1 have been reported (Table 2). Of note is that the sample size was under 100 in 19 out of 22 studies. All African populations share similar characteristics compared to UK populations with lower KIR2DS1 and KIR3DS1 carrier frequencies; the highest value for KIR2DS1 was 0.28 (Congo Mbuti) and 0.23 for KIR3DS1 (Ethiopian) compared with, respectively, 0.42 and 0.44 for the UK population. The variability of these frequencies between the African populations may be visualized using principal component analysis (Fig. 1). The Ugandan population localizes to an intermediate position, between Central and West African populations and the East African populations. Therefore, in terms of KIR gene frequencies, the Ugandan population can be regarded as intermediate to these populations. The history of human migration in Africa is consistent with this observation because Uganda is an East African country known to have been populated from the Bantu migrations from West and Central Africa (Campbell and Tishkoff 2008). Furthermore, it is in both the northern and southern hemispheres, being situated on the equatorial line.Table 2

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