Dataset Information

Epimutations Define a Fast-Ticking Molecular Clock in Plants.

ABSTRACT: Stochastic gains and losses of DNA methylation at CG dinucleotides are a frequent occurrence in plants. These spontaneous 'epimutations' occur at a rate that is 100 000 times higher than the genetic mutation rate, are effectively neutral at the genome-wide scale, and are stably inherited across mitotic and meiotic cell divisions. Mathematical models have been extraordinarily successful at describing how epimutations accumulate in plant genomes over time, making this process one of the most predictable epigenetic phenomena to date. Here, we propose that their high rate and effective neutrality make epimutations a powerful new molecular clock for timing evolutionary events of the recent past and for age dating of long-lived perennials such as trees.

SUBMITTER: Yao N

PROVIDER: S-EPMC8282728 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Epimutations Define a Fast-Ticking Molecular Clock in Plants.

Yao Nan N Schmitz Robert J RJ Johannes Frank F

Trends in genetics : TIG 20210517 8

Stochastic gains and losses of DNA methylation at CG dinucleotides are a frequent occurrence in plants. These spontaneous 'epimutations' occur at a rate that is 100 000 times higher than the genetic mutation rate, are effectively neutral at the genome-wide scale, and are stably inherited across mitotic and meiotic cell divisions. Mathematical models have been extraordinarily successful at describing how epimutations accumulate in plant genomes over time, making this process one of the most predi ...[more]

PMID: 34016450

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Project description:IntroductionUnderstanding the determinants of timely antiretroviral therapy (ART) initiation is useful for HIV programmes intent on developing models of care that reduce delays in treatment initiation while maintaining a high quality of care. We analysed patient- and facility-level determinants of time to ART initiation among patients who initiated ART in Kenya.MethodsWe collected facility-level information and conducted a retrospective chart review of adults initiating ART between 2007 and 2012 at 51 health facilities in Kenya. We evaluated the association between patient- and facility-level covariates at the time of ART eligibility and time to ART initiation. We also explored the determinants associated with timeliness of ART initiation.ResultsThe analysis included 11,942 patients. The median age at the time eligibility was first determined was 37 years (interquartile range [IQR] 31-45). Overall, 75% of patients initiated ART within two months of eligibility. The median CD4 cell count at the time eligibility was first determined rose from 132 (IQR 51-217) in 2007 to 195 (IQR 91-286) in 2011 to 2012 (p<0.001). The cumulative probability of ART initiation among treatment-eligible patients increased over time: 87.1% (95% confidence interval [CI] 85.1-89.0%) in 2007; 96.8% (96.0-97.5%) in 2008; 97.1% (96.3-97.7%) in 2009; 98.5% (98.0 -98.9%) in 2010; and 99.7% (95% CI 99.4 -99.8%) in 2011 to 2012 (p<0.0001). In multivariate analyses, attending a health facility with high ART patient volumes within two months of eligibility was considered the key facility-level determinant of ART initiation (adjusted odds ratio 0.57, 95% CI 0.45-0.72, p<0.001). Patient-level determinants included being eligible for ART in the years subsequent to 2007, advanced World Health Organization clinical stage and low CD4 cell count at the time eligibility was first determined.ConclusionsOverall, the time between treatment eligibility and ART initiation decreased substantially in Kenya between 2007 and 2012, with uniform gains across different types of health facilities. Our findings highlight the slow increase in CD4 cell counts at the time of ART eligibility over time, indicating that a large number of patients are still beginning ART with advanced HIV disease. Our findings also support the decentralisation of ART services at all health facilities that have the capacity to initiate treatment. Continued evaluation of programme- and country-level data is needed to monitor timeliness of ART initiation as countries continue to expand treatment access.

Dataset Information

Epimutations Define a Fast-Ticking Molecular Clock in Plants.

Publications

Epimutations Define a Fast-Ticking Molecular Clock in Plants.

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