The genes of interest were mapped onto the figure using positions

The genes of interest were mapped onto the figure using positions based on the UCSC genome browser build hg18. Plot comparing regions with signatures of selection A plot comparing the number of SNPs contained in each region under putative selection and the selleck bio length in kb of the region under putative selection was constructed using the R software package. For each region under putative selection, genes overlapping with the region were counted, using gene positions provided by the UCSC human genome build 18. The count of genes was listed in the plot. Other genomic scans for selection We incorporated the results of other selection scans that had examined SNP genotypes among the Biaka Pygmy population. Pickrell et al.

had conducted genomic scans of the HGDP SNP dataset, using integrated haplo type score and cross population extended haplo type homozygosity tests that relied on a sliding window size of 200 kb to identify genes under regions showing signatures of selection, with increments of 100 kb or 200 kb used for alternative analyses. We identified HGAHs and HDFs among genes identified by Pickrell et al. as under potential selection in the Biaka. Additionally, Lopez Herraez et al. had geno typed five individuals from each HGDP population, in cluding five Biaka, using the Affymetrix GeneChip Human Mapping 500 K array set, concatenating this dataset with that of the Illumina chip. Signatures of selection had been inferred from this data using a modified lnRsb approach, which is similar to the XP EHH method. We identified HGAHs and HDFs among the genes previously reported by Lopez Herraez et al.

as displaying signatures of selec tion in the Biaka. PCR and sequencing of genes We also examined sequence diversity in Pygmies for sev eral human genes associated with HIV 1, as well as two HDFs in 5 Biaka Pygmy and 5 Mbuti Pygmy DNA samples. Sequences and SNPs of each gene were searched and retrieved from NCBI entries and the UCSC Genome Browser. The mutation CCR2 64V to CCR2 64I delays the progression of AIDS in HIV 1 infected individuals. Thus exon 2 that includes this region was sequenced in CCR2. For CCR5, exon 4 contains the open reading frame and was sequenced. For CUL5, primers were designed to include the putative regions of interaction with HIV 1 vif or with elongins.

Mutation analysis has suggested that both the N terminal RING and C terminal SPRY domains of rhe sus TRIM5 alpha contribute to its HIV 1 inhibitory ac tivity, thus the regions that code for these domains were sequenced in TRIM5. The ubiquitin enzyme 2 vari ant domain in TSG101 was sequenced since it binds to the p6 domain of the structural Gag protein of HIV 1. ITGAX is reported to be progressively depleted in HIV 1 infection, and the loss of ITGAX in HIV infection may contribute to AIDS pro gression. OPRM1 was sequenced Brefeldin_A since through the activation of OPRM1, opiate drugs are known to in crease HIV 1 replication in macrophages.

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