Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Modifier genes analysis by PCR-RFLP adapted from previously published techniques [21]–[24].

<p>Modifier genes analysis by PCR-RFLP adapted from previously published techniques <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090945#pone.0090945-Sandford1" target="_blank">[21]</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090945#pone.0090945-Chen1" target="_blank">[24]</a>.</p

TNF1/TNF2 association values using dominant, additive and recessive models.

1<p>odds ratio.</p>2<p>Chi-Squared P.</p>3<p>Bonf. P.</p>4<p>Correl/Trend P.</p

PCR-RFLP for the modifier genes analysis.

<p>1A: the 134 bp PCR product from exon 1 of the MBL1 gene was digested with <i>Mwo</i> I, <i>Ban</i> I and <i>Mbo</i> II for detection of polymorphisms in the 52, 54 and 57 codons. 1B: the 816 bp PCR product from promoter region of the IL-8 gene was digested with <i>Mfe</i> I for detection of the −251 polymorphism. 1C: the 142 bp PCR product from promoter region of the TNFα gene was digested with <i>Nco</i> I for detection of the −308 polymorphism (TNF2); the 98 bp PCR product from the SERPINA1 gene was digested with <i>Taq</i> I^α for detection of the S genetic variant; the 144 bp PCR product from the SERPINA1 gene was digested with <i>Taq</i> I^α enzyme for detection of the Z genetic variant. Mw1 is the molecular marker pBs+<i>Msp</i> I, Mw2 is the molecular marker λ+<i>Pst</i> I. P_MBL, P_IL8, P_TNF, P_AATS and P_AATZ are undigested PCR products. The Z allele was not detected.</p

Modifier gene genotype frequencies (%) in CF patients and control subjects; OR, Hardy–Weinberg Equilibrium (HWE) and results of the association test with Dominant Model <i>P</i>-values.

<p>CF, cystic fibrosis; OR, Odds Ratio; CI, confidence interval.</p>a<p>TNF1 −308 G: (dd) vs. (DD, Dd),</p>b<p>TNF2 −308 A: (DD, Dd) vs. (dd).</p><p>HW-P: <i>P</i>-value for the Hardy-Weinberg equilibrium.</p><p>X² Bonf. P = Chi squared test with a Bonferroni-corrected <i>P</i>-value.</p

The tumor necrosis factor α (-308 A/G) polymorphism is associated with cystic fibrosis in Mexican patients.

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (-251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP.The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25-9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease.An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients

Early stage litter decomposition across biomes

[Departement_IRSTEA]Territoires [TR1_IRSTEA]SEDYVINInternational audienceThrough litter decomposition enormous amounts of carbon is emitted to the atmosphere. Numerous large-scale decomposition experiments have been conducted focusing on this fundamental soil process in order to understand the controls on the terrestrial carbon transfer to the atmosphere. However, previous studies were mostly based on site-specific litter and methodologies, adding major uncertainty to syntheses, comparisons and meta-analyses across different experiments and sites. In the TeaComposition initiative, the potential litter decomposition is investigated by using standardized substrates (Rooibos and Green tea) for comparison of litter mass loss at 336 sites (ranging fro