Perceived quality of life among caregivers of children with a childhood-onset dystrophinopathy: a double ABCX model of caregiver stressors and perceived resources

Background: Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are recessive X-linked disorders characterized by progressive muscle weakness and ultimately cardiac and respiratory failure. Immediate family members are often primary caregivers of individuals with a dystrophinopathy. Methods: We explored the impact of this role by inviting primary caregivers (n = 209) of males diagnosed with childhood-onset dystrophinopathy who were identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) to complete a mailed questionnaire measuring perceived social support and stress, spirituality, and family quality of life (FQoL). Bivariate and multivariate analyses examined associations between study variables using the Double ABCX model as an analytic framework. Results: Higher stressor pile-up was associated with lower perceived social support (r = -0.29, p 0.05). FQoL was positively associated with all support measures (correlations ranged from: 0.25 to 0.58, p-values 0.01-0.001) and negatively associated with perceived stress and control (r = -0.49, p <.001). The association between stressor pile-up and FQoL was completely mediated through global perceived social support, supportive family relationships, and perceived stress and control; supportive non-family relationships did not remain statistically significant after controlling for other mediators. Conclusions: Findings suggest caregiver adaptation to a dystrophinopathy diagnosis can be optimized by increased perceived control, supporting family resources, and creation of a healthy family identity. Our findings will help identify areas for family intervention and guide clinicians in identifying resources that minimize stress and maximize family adaptation.CDC [5U01DD000831, 5U01DD000187, 5U01DD000189, 5U01DD000191, 5U01DD000190]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

CpG Islands: A Historical Perspective

The discovery of CpG islands (CGIs) and the study of their structure and properties run parallel to the development of molecular biology in the last two decades of the twentieth century and to the development of high-throughput genomic technologies at the turn of the millennium. First identified as discrete G + C-rich regions of unmethylated DNA in several vertebrates, CGIs were soon found to display additional distinctive chromatin features from the rest of the genome in terms of accessibility and of the epigenetic modifications of their histones. These features, together with their colocalization with promoters and with origins of DNA replication in mammals, highlighted their relevance in the regulation of genomic processes. Recent approaches have shown with unprecedented detail the dynamics and diversity of the epigenetic landscape of CGIs during normal development and under pathological conditions. Also, comparative analyses across species have started revealing how CGIs evolve and contribute to the evolution of the vertebrate genome.Peer reviewe

DNA methylation: insights into human evolution

A fundamental initiative for evolutionary biologists is to understand the molecular basis underlying phenotypic diversity. A long-standing hypothesis states that species-specific traits may be explained by differences in gene regulation rather than differences at the protein level. Over the past few years, evolutionary studies have shifted from mere sequence comparisons to integrative analyses in which gene regulation is key to understanding species evolution. DNA methylation is an important epigenetic modification involved in the regulation of numerous biological processes. Nevertheless, the evolution of the human methylome and the processes driving such changes are poorly understood. Here, we review the close interplay between Cytosine-phosphate-Guanine (CpG) methylation and the underlying genome sequence, as well as its evolutionary impact. We also summarize the latest advances in the field, revisiting the main literature on human and nonhuman primates. We hope to encourage the scientific community to address the many challenges posed by the field of comparative epigenomics.TMB is supported by ICREA (www.icrea.cat), EMBO YIP (www.embo.org) 2013, MICINN BFU2014-55090-P (www.mecd.gob.es), BFU2015-7116-ERC and BFU2015-6215-ERC. AJS is supported by NIH (www.nih.gov) grants DA033660, HG006696, HD073731, and MH097018, and research grant 6-FY13-92 from the March of Dimes Foundation. IHH is supported by AGAUR (Generalitat de Catalunya, Spain; www.gencat.cat/agaur/) and RGP by a fellowship from MICINN (www.mecd.gob.es). We also acknowledge the Barcelona Zoo (Ajuntament de Barcelona) for an award to IHH