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Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children.

ABSTRACT: CCL3L and CCL4L genes encode HIV-suppressive chemokines, colocalize on chromosome 17q12 and have copy number variation. Copy number variation of CCL3L associates with HIV-AIDS susceptibility. Here, we determined the influence of the combinatorial content of distinct CCL3L and CCL4L genes on HIV-AIDS susceptibility.By designing gene-specific assays, the association between doses of all CCL3L or CCL4L genes or their individual duplicated components (CCL3La/b and CCL4La/b) with HIV-AIDS susceptibility was determined in 298 perinatally exposed Ukrainian children.The odds of transmission was increased in children with less than two copies of CCL3L or CCL4L, compared with those with at least two copies, and 10-fold higher when both mother and offspring had less than two CCL3L or CCL4L copies, compared with mother-child pairs with at least two copies. The extent of the pair-wise correlations between CCL3La, CCL3Lb, CCL4La and CCL4Lb copy number varied extensively, with an inverse correlation between CCL4L genes that transcribe a classical chemokine (CCL4La) versus aberrantly-spliced transcripts (CCL4Lb). Children possessing only CCL4Lb progressed four times faster to AIDS than those with only CCL4La. A lower content of CCL3L and CCL4L genes that transcribe classical chemokines was associated with enhanced HIV-AIDS susceptibility.Transmission risk is greatest when mother and offspring both have low CCL3L or CCL4L gene doses. The impact on HIV-AIDS susceptibility of the chemokine gene-rich locus on 17q12 is dependent on the balance between the doses of genes conferring protective (CCL3La and CCL4La) versus detrimental (CCL4Lb) effects. Hence, the combinatorial genomic content of distinct genes within a copy number variable region may determine disease susceptibility.

SUBMITTER: Shostakovich-Koretskaya L

PROVIDER: S-EPMC2929972 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children.

Shostakovich-Koretskaya Ludmila L Catano Gabriel G Chykarenko Zoya A ZA He Weijing W Gornalusse German G Mummidi Srinivas S Sanchez Racquel R Dolan Matthew J MJ Ahuja Seema S SS Clark Robert A RA Kulkarni Hemant H Ahuja Sunil K SK

AIDS (London, England) 20090301 6

<h4>Objective</h4>CCL3L and CCL4L genes encode HIV-suppressive chemokines, colocalize on chromosome 17q12 and have copy number variation. Copy number variation of CCL3L associates with HIV-AIDS susceptibility. Here, we determined the influence of the combinatorial content of distinct CCL3L and CCL4L genes on HIV-AIDS susceptibility.<h4>Methods</h4>By designing gene-specific assays, the association between doses of all CCL3L or CCL4L genes or their individual duplicated components (CCL3La/b and C ...[more]

PMID: 19279442

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Project description:BackgroundDespite the increasing number of mobile health applications, the validity of their content is understudied. The objective of this study was to rate the content of HIV/AIDS-related mobile applications and to determine the extent to which evidence-based medicine is being incorporated into their content using a new tool called the Evidence-based content rating tool of mobile health applications (EBCRT-mHealth).MethodsAll available HIV/AIDS-related applications in Iran from Cafe Bazaar and Google Play Store were evaluated. This study was first conducted in 2018, then after almost two years in 2021 was done again. In this study, researchers developed the EBCRT-mHealth tool to rate the content of applications based on the evidence-based medicine pyramid. Its reliability was calculated (α = 0.78), and five specialists confirmed its validity. Two reviewers independently reviewed all HIV/AIDS applications directly downloaded and installed from the Google Play Store and Cafe Bazaar.ResultsOut of 980 retrieved applications, in 2018, 85, and in 2021, 78 applications were included in the study. Only in 17 (28%) out of the 60 in 2018, and 25 (51%) in 2021 Google Play store applications the source of content information was mentioned. All Cafe Bazaar mobile applications mentioned the source of information. The mean rating of all application content in 2018 was 2.38 (SD = 0.74), and in 2021 was 2.90 (SD = 1.35) out of 5. The mean rating of the content of Cafe Bazaar applications in 2018 was 2.10 (SD = 0.49), and in 2021 was 1.94 (SD = 0.29). The mean content rating of Google Play store applications in 2018 was 2.50 (SD = 0.80) and in 2021 was 3.86 (SD = 1.18).ConclusionAfter two years, the rating of the content of HIV/AIDS-related applications available in Iran that existed in Cafe Bazaar decreased from "poor" to "inappropriate". Also, the content score of the Google Play Store applications increased from "poor" to "good". It is critical to ensure the credibility of the sources used in developing their content and removing applications with inappropriate and unreliable content from the App Stores. Also, mobile health application developers should use the highest quality information in their applications.

Project description:Replication initiation in archaea involves a protein named ORC, Cdc6, or ORC1/Cdc6, which is homologous to the eukaryotic origin recognition complex (ORC) proteins and to the eukaryotic Cdc6. Archaeal replication origins are comprised of origin repeat regions and adjacent orc genes. Some archaea contain a single replication origin and a single orc gene, while others have more than one of each. Haloferax volcanii is exceptional because it contains, in total, six replication origins on three chromosomes and 16 orc genes. Phylogenetic trees were constructed that showed that orc gene duplications occurred at very different times in evolution. To unravel the influence of the ORC proteins on chromosome copy number and cellular fitness, it was attempted to generate deletion mutants of all 16 genes. A total of 12 single-gene deletion mutants could be generated, and only three orc gene turned out to be essential. For one gene, the deletion analysis failed. Growth analyses revealed that no deletion mutant had a growth defect, but some had a slight growth advantage compared to the wild type. Quantification of the chromosome copy numbers in the deletion mutants showed that all 12 ORC proteins influenced the copy numbers of one, two, or all three chromosomes. The lack of an ORC led to an increase or decrease of chromosome copy number. Therefore, chromosome copy numbers in Hfxvolcanii are regulated by an intricate network of ORC proteins. This is in contrast to other archaea, in which ORC proteins typically bind specifically to the adjacent origin.IMPORTANCE The core origins of archaea are comprised of a repeat region and an adjacent gene for an origin recognition complex (ORC) protein, which is homologous to eukaryotic ORC proteins. Haloferax volcanii is exceptional because it contains six replication origins on three chromosomes and an additional 10 orc genes that are not adjacent to an origin. This unique ORC protein repertoire was used to unravel the importance of core origin orc genes and of origin-remote orc genes. Remarkably, all ORC proteins influenced the copy number of at least one chromosome. Some of them influenced those of all three chromosomes, showing that cross-regulation in trans exists in Hfx. volcanii Furthermore, the evolution of the archaeal ORC protein family was analyzed.

Dataset Information

Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children.

Publications

Combinatorial content of CCL3L and CCL4L gene copy numbers influence HIV-AIDS susceptibility in Ukrainian children.

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