The Vocalism of Strong Verbs in Afar

Proceedings of the Twenty-Seventh Annual Meeting of the Berkeley Linguistics Society: Special Session on Afroasiatic Languages (2001

Association Study of Common Genetic Variants and HIV- 1 Acquisition in 6,300 Infected Cases and 7,200 Controls

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10−11). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception ofCCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size

Création d'un système informatique d'aide à la décision pour l'unité de préparation des chimiothérapies du CHU de Clermont-Ferrand

La préparation des chimiothérapies est une activité très réglementée au sein des Pharmacies à Usage Intérieur des établissements de santé. Celle-ci nécéssite des moyens techniques et humains importants, afin d'assurer une qualité optimale des préparations aux patients cancéreux. la centralisation de cette préparation apporte des critères de qualité et de protection indéniables, ainsi qu'un avantage économique important. Afin de mieux maîtriser son outil de production, le pharmacien responsable de l'Unité de Préparation des Chimiothérapies a besoin d'un système d'analyse fiable et rapide lui permettant de mesurer son activité, ainsi que la qualité de son organisation et de sa production en temps réel. Après recensement des différentes sources d'informations à sa disposition, un Système Informatique d'Aide à la Décision, composé d'un ensemble d'indicateurs, regroupés au sein de tableaux de bord, a été mis en place. Le but est de lui donner une vision synthétique des différents domaines de son activité. Ce travail s'inscrit dans une démarche d'assurance qualité qui devra se poursuivre, et le système mis en place devra évoluer pour s'adapter parfaitement aux besoins de l'utilisateur, et atteindre un degré de maturité qui en fera un véritable outil de pilotage pour le pharmacien.CLERMONT FD-BCIU-Santé (631132104) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

List of SNP/gene pairs associated with AIDS progression.

<p>(*) Note that rs3749971 is in linkage disequilibrium with rs3130350 and is therefore not considered an independent finding (see text).</p><p>The genetic association is linked back to its association with gene expression levels to provide an association between transcription levels (we use the word ‘regulation’ for convenience’s sake) and AIDS progression.</p

Statistical significance of our associations.

<p>Histogram of the number of SNPs that pass the significance criterion for this study using phenotype and SNP randomisations. These results provide us with a way to estimate the sensitivity of our study (diamond): it would be extremely unlikely for our eight independent findings to arise by chance alone (<i>p</i> = 0.001).</p

Schematic summary of our methodology.

<p>The data from three databases are integrated to provide us with functional SNPs likely to be associated with changes in gene transcription in the tissue of interest. Using the SNAP Pairwise LD server, we only kept independent SNPs by removing superfluous SNPs that were in linkage disequilibrium (<i>r</i>² ≥ 0.2). Among those SNPs, associations with slow and non-progression towards AIDS are sought and replicated. Randomisations are carried out in order to evaluate the statistical robustness of our results. Finally, the genetic associations are used to link progression to AIDS and gene expression in candidate genes.</p

Identification of Genes Whose Expression Profile Is Associated with Non-Progression towards AIDS Using eQTLs

<div><p>Background</p><p>Many genome-wide association studies have been performed on progression towards the acquired immune deficiency syndrome (AIDS) and they mainly identified associations within the <i>HLA</i> loci. In this study, we demonstrate that the integration of biological information, namely gene expression data, can enhance the sensitivity of genetic studies to unravel new genetic associations relevant to AIDS.</p><p>Methods</p><p>We collated the biological information compiled from three databases of expression quantitative trait loci (eQTLs) involved in cells of the immune system. We derived a list of single nucleotide polymorphisms (SNPs) that are functional in that they correlate with differential expression of genes in at least two of the databases. We tested the association of those SNPs with AIDS progression in two cohorts, GRIV and ACS. Tests on permuted phenotypes of the GRIV and ACS cohorts or on randomised sets of equivalent SNPs allowed us to assess the statistical robustness of this method and to estimate the true positive rate.</p><p>Results</p><p>Eight genes were identified with high confidence (<i>p</i> = 0.001, rate of true positives 75%). Some of those genes had previously been linked with HIV infection. Notably, <i>ENTPD4</i> belongs to the same family as <i>CD39</i>, whose expression has already been associated with AIDS progression; while <i>DNAJB12</i> is part of the HSP90 pathway, which is involved in the control of HIV latency. Our study also drew our attention to lesser-known functions such as mitochondrial ribosomal proteins and a zinc finger protein, ZFP57, which could be central to the effectiveness of HIV infection. Interestingly, for six out of those eight genes, down-regulation is associated with non-progression, which makes them appealing targets to develop drugs against HIV.</p></div