Genetic variation within <i>HLA-C</i> 3′ UTR sequences of the <i>HLA-C</i> alleles observed in the Caucasian South African population group.

1<p>positions are given relative to the start of the HLA-C 3′ UTR.</p>2<p><i>HLA-C</i> alleles <i>C*02∶02</i> and <i>C*03∶04</i> were found to have more than one 3′ UTR sequence.</p>3<p>where more than one allele has been observed alleles are reported using standard IUB ambiguity codes.</p>4<p>I refers to an insertion and D to a deletion.</p

Genetic Variability in Markers of HLA-C Expression in Two Diverse South African Populations

<div><p>An insertion-deletion (indel) polymorphism within the 3′ untranslated region (UTR) of <i>HLA-C</i> has been shown to be involved in the regulation of HLA-C expression. Individuals who carry a deletion at this position exhibit increased HLA-C expression, which associates with lower viral set point in HIV-1 infected individuals. This <i>263</i> indel (rs67384697) is reported to be in strong linkage disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases upstream of <i>HLA-C</i> (<i>-35T/C</i>; rs9264942) in Caucasian individuals, making this SNP a potential marker for both HLA-C expression and HIV-1 disease progression. We therefore examined genetic variation within the <i>HLA-C</i> 3′ UTR of 265 Black and Caucasian South Africans by direct sequencing and identified haplotypes encompassing the <i>263</i> indel and another indel at position 230 in both populations. Concomitant evaluation of variability at the <i>−35</i> SNP revealed this polymorphism to be an inappropriate marker for the <i>263</i> indel in these populations. These findings provide important insights into genetic variability within the regulatory regions of <i>HLA-C</i> that have potential implications for our understanding of the regulation of HLA-C expression and its impact on HIV-1 disease progression.</p></div

Linkage disequilibrium between the <i>-35</i> SNP and the <i>HLA-C</i> alleles present in the Black and Caucasian South African population groups.

1<p>the total number of individuals genotyped in each population group.</p>2<p>the observed frequency of each two-locus haplotype.</p>3<p>Lewontin's D' measure of linkage disequilibrium <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067780#pone.0067780-Lewontin1" target="_blank">[19]</a>.</p>4<p>p-values are calculated using an exact test for linkage disequilibrium <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067780#pone.0067780-Slatkin1" target="_blank">[20]</a>, and are significant at p<0.05.</p>5<p>the number of chromosomes on which the two-locus haplotype was found to occur.</p

The haplotypes identified within the <i>HLA-C</i> 3′ UTR.

<p>The positions involved in the two haplotypes identified are indicated in colour. The haplotype encompassing the <i>263</i> indel is shown in pink, while the haplotype encompassing the <i>230</i> indel is shown in blue. The major and minor alleles at each position are also indicated. Positions were only included in the haplotypes if both D' and r² measures of pairwise LD were equal to 1. Polymorphic positions are indicated by their position relative to the start of the <i>HLA-C</i> 3′ UTR.</p

Genetic variation within <i>HLA-C</i> 3′ UTR sequences of the <i>HLA-C</i> alleles observed in the Black South African population group.

1<p>positions are given relative to the start of the HLA-C 3′ UTR.</p>2<p><i>HLA-C</i> alleles <i>C*02∶02, C*02∶10, C*03∶04, C*07∶01, C*16∶01</i> and <i>C*18∶01</i> were found to have more than one 3′ UTR sequence.</p>3<p>where more than one allele has been observed alleles are reported using standard IUB ambiguity codes.</p>4<p>I refers to an insertion and D to a deletion.</p

Characteristics of 146 treated HIV-infected children in Johannesburg, South Africa, at the time of measurement of cell-associated HIV-1 DNA (current time) and at the time of antiretroviral therapy (ART) initiation.

<p>Characteristics of 146 treated HIV-infected children in Johannesburg, South Africa, at the time of measurement of cell-associated HIV-1 DNA (current time) and at the time of antiretroviral therapy (ART) initiation.</p

Comparison of <i>reverse transcriptase</i>-based single round qPCR (a and b) and sn-qPCR (c and d) assays designed to quantify subtype C HIV-1 proviral DNA.

<p>Amplification curves (a and c) of ten-fold diluted plasmid (p8MJ4) DNA harboring subtype C HIV-1 gag-pol gene and standard curves generated (b and d) from respective curves. Grey zone shows that the cycle threshold (C_T) region where 10⁵ plasmid DNA copies are amplified in the single round qPCR (a) is equivalent to the C_T region where a single copy (10°) is amplified using the sn-qPCR assay. Eff = PCR efficiency.</p

Associations between age at starting ART and cell-associated HIV-1 DNA levels after a median of 4.3 years of treatment among 146 HIV-infected children.

<p>a: Scatterplot of HIV-1 DNA log₁₀ copies/10⁶ cells (Y-axis) by age at ART start in months (x-axis). LOcally WEighted Scatter-plot Smoother (LOWESS) and linear regression prediction lines are shown in blue and red, respectively; and the grey area shows the 95% prediction elipse. b: Box and whisker plot of HIV-1 DNA log₁₀ copies/10⁶ cells by age at ART start groups; c: Histograms and estimated normal and kernel distributions of HIV-1 DNA log₁₀ copies/10⁶ cells among those who started ART <4.5 and ≥4.5 months of age.</p

Scatterplots showing associations between HIV-1 DNA log₁₀ copies/10⁶ cells and a: Time on ART in years; b: Pre-ART HIV-1 RNA copies/ml and c: Pre-ART CD4 count in cells/mm3.

<p>LOcally WEighted Scatter-plot Smoother (LOWESS) and linear regression prediction lines shown in blue and red, respectively.; grey area shows the 95% prediction elipse.</p