<i>elt-2(RNAi)</i> animals are more susceptible than wild-type nematodes to a variety of pathogens.

<div><p>(<b>A</b>)Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were exposed to <i>P. aeruginosa</i> PA14 (P = 0.0001).</p> <p>(<b>B</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were exposed to <i>E. faecalis</i> OG1RF (P<0.0001).</p> <p>(<b>C</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were exposed to <i>C. neoformans</i> H99 (P<0.0001).</p> <p>60–120 nematodes were used for each condition.</p> <p>Results are representative of at least 3 independent experiments.</p></div

<i>elt-2</i>(RNAi) animals are hypersusceptible to <i>S. enterica-</i>mediated killing and are colonized by <i>E. coli</i>.

<div><p>(<b>A</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were exposed to <i>S. enterica</i> SL1344 (P<0.0001).</p> <p>60 nematodes were used for each condition. Results are representative of at least 3 independent experiments.</p> <p>(<b>B</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were placed on FUdR containing plates with lawns of heat-killed <i>E. coli</i> OP50 (P = 0.0011).</p> <p>20 nematodes were used for each condition. Results are representative of at least 3 independent experiments.</p> <p>(<b>C</b>) and (<b>D</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control (C) or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA (D) were exposed to <i>E. coli</i> expressing DSred for 24 hours, and then visualized using a Leica TCS SL spectral confocal microscope (bar = 50 µm).</p> <p>(<b>E</b>) Wild-type nematodes grown on <i>E. coli</i> carrying a vector control or on <i>E. coli</i> expressing <i>elt-2</i> double-stranded RNA were transferred to a clean LB plate either immediately or after 24 hours exposure to <i>E. coli</i> OP50 (+24 hrs), where they were allowed to defecate for 2 hours.</p> <p>Plates then were placed at 37°C overnight and colonies counted.</p> <p>The combined data from 10 individual animals are shown, and data were normalized to the median colony count for the vector control at each timepoint.</p> <p>Error bars represent SEM.</p> <p>Results are representative of at least 3 independent experiments.</p></div

Assessment of Genotype Imputation Performance Using 1000 Genomes in African American Studies

<div><p>Genotype imputation, used in genome-wide association studies to expand coverage of single nucleotide polymorphisms (SNPs), has performed poorly in African Americans compared to less admixed populations. Overall, imputation has typically relied on HapMap reference haplotype panels from Africans (YRI), European Americans (CEU), and Asians (CHB/JPT). The 1000 Genomes project offers a wider range of reference populations, such as African Americans (ASW), but their imputation performance has had limited evaluation. Using 595 African Americans genotyped on Illumina’s HumanHap550v3 BeadChip, we compared imputation results from four software programs (IMPUTE2, BEAGLE, MaCH, and MaCH-Admix) and three reference panels consisting of different combinations of 1000 Genomes populations (February 2012 release): (1) 3 specifically selected populations (YRI, CEU, and ASW); (2) 8 populations of diverse African (AFR) or European (AFR) descent; and (3) all 14 available populations (ALL). Based on chromosome 22, we calculated three performance metrics: (1) concordance (percentage of masked genotyped SNPs with imputed and true genotype agreement); (2) imputation quality score (IQS; concordance adjusted for chance agreement, which is particularly informative for low minor allele frequency [MAF] SNPs); and (3) average r2hat (estimated correlation between the imputed and true genotypes, for all imputed SNPs). Across the reference panels, IMPUTE2 and MaCH had the highest concordance (91%–93%), but IMPUTE2 had the highest IQS (81%–83%) and average r2hat (0.68 using YRI+ASW+CEU, 0.62 using AFR+EUR, and 0.55 using ALL). Imputation quality for most programs was reduced by the addition of more distantly related reference populations, due entirely to the introduction of low frequency SNPs (MAF≤2%) that are monomorphic in the more closely related panels. While imputation was optimized by using IMPUTE2 with reference to the ALL panel (average r2hat = 0.86 for SNPs with MAF>2%), use of the ALL panel for African American studies requires careful interpretation of the population specificity and imputation quality of low frequency SNPs.</p> </div

Average r2hat values resulting from four different imputation programs and three different 1000 Genomes (February 2012) reference panels.

<p>r2hat values were averaged across all imputed SNPs on chromosome 22. The number of subjects corresponding to each reference panel is shown in parentheses.</p

Concordance resulting from four different imputation programs and three different 1000 Genomes (February 2012 release) reference panels.

<p>Concordance rates were based on masking 2% of the genotyped SNPs on chromosome 22 and comparing imputed and true genotypes. The number of subjects corresponding to each reference panel is shown in parentheses.</p

Average r2hat, based on imputation using IMPUTE2, across the minor allele frequency (MAF) spectrum.

<p>Imputation was conducted for all SNPs available on the YRI+CEU+ASW (N = 234, in red), AFR+EUR (N = 625, in green), or the ALL (N = 1,092, in blue) reference panel from 1000 Genomes. Imputed polymorphic SNPs were divided into MAF intervals of 1%, and their average r2hat values were calculated within each interval.</p

Imputation quality score (IQS) resulting from four different imputation programs and three different 1000 Genomes (February 2012) reference panels.

<p>IQS results were based on masking 2% of the genotyped SNPs and adjusting the concordance rate chance agreement between imputed and true genotypes. The number of subjects corresponding to each reference panel is shown in parentheses.</p

Characteristics of participants in the Urban Health Study and the Women’s Interagency HIV Study.

<p>Characteristics of participants in the Urban Health Study and the Women’s Interagency HIV Study.</p

Manhattan plot showing the meta-analysis results of approximately 8 million SNPs and indels tested for association with HIV-1 acquisition in 2,004 African Americans and 1,132 European Americans from the Urban Health Study.

<p>The–log₁₀ (<i>P</i> value) is plotted by chromosomal position of SNPs (shown as circles) and indels (shown as triangles). The SNPs and indels selected for replication testing from 8 gene regions are highlighted in red. The gene region above the solid grey line (<i>P</i><5x10^-8) exceeded the threshold for genome-wide statistical significance. In addition, the 6 gene regions above the dashed black line (<i>P</i><1x10^-6) and the region around the top genotyped SNP (<i>P</i> = 1x10^-5 on chromosome 9) were selected for replication testing.</p

Overview of Study Design.

<p>AA represents African Americans, EA represents European Americans, and UofC represents University of Chicago.</p