18 research outputs found
Multilocus loss of DNA methylation in individuals with mutations in the histone H3 Lysine 4 Demethylase KDM5C
Don’t brush off buccal data heterogeneity
Buccal epithelial cells are among the most clinically accessible tissues and are increasingly being used to identify epigenetic disease patterns. However, substantial variation in buccal DNA methylation patterns indicates heterogeneity of cell types within and between samples, raising questions of data quality. We systematically estimated cell-type composition for a large collection of buccal and saliva samples from 11 published studies of DNA methylation. In these we identified numerous cases of buccal samples with questionable purity, which may be affected by sampling from individuals with neurodevelopmental disorders, and by the brushes used for sample collection. Further challenges are involved in comparisons with tissues such as saliva, in which buccal component varies widely. We propose a reference-based method of correcting for buccal purity that reduces unwanted variation while preserving cross-tissue differences. Our work demonstrates the wide variation of buccal quality in epigenetic studies and suggests a possible approach to overcome this issue
Cross-Reactive DNA Microarray Probes Lead to False Discovery of Autosomal Sex-Associated DNA Methylation
Fluorogram of amplification of intermethylated sites (AIMS) gel showing human MCF-7 and MDA-MB 231 breast cancer cells treated with 5 ÎĽmol/l benzopyrene for 48, 72 and 96 hours (+)
<p><b>Copyright information:</b></p><p>Taken from "Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites"</p><p>Breast Cancer Research 2004;6(4):R329-R337.</p><p>Published online 30 Apr 2004</p><p>PMCID:PMC468641.</p><p>Copyright © 2004 Sadikovic et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</p> Banding patterns differ increasingly as the culture period is extended, reflecting increasing hypomethylation of genomic DNA. Arrows indicate decreases in or loss of band intensity, which that are indicative of hypomethylation. Arrowheads indicate loss of bands and hypomethylation that is apparently dependent on culture conditions
Neurocognitive Late Effects of Chemotherapy in Survivors of Acute Lymphoblastic Leukemia: Focus on Methotrexate
Childhood cancer survivors frequently experience long-lasting consequences of chemotherapy on health outcomes.Neurocognitive late effects of chemotherapy occur in 40 – 60% of acute lymphoblastic leukemia (ALL) survivors. These deficits affect mental health, school performance, job success, and are associated with poor quality of life, therefore presenting a clinical challenge for psychiatrists. However, not all cancer survivors are impacted by treatment in the same manner and emerging evidence suggests that genetic variation may modulate neurocognitive outcomes. Much like other complex psychopathologies, neurocognitive deficits in cancer survivors are the result of complex interactions between genetic and environmental variables. This review describes adverse neurocognitive outcomes observed in survivors of acute lymphoblastic leukemia (ALL) and discusses genetic variability in biochemical pathways targeted by chemotherapeutic agents as a possible mechanism contributing to psychopathology in ALL survivors
Cross-Reactive DNA Microarray Probes Lead to False Discovery of Autosomal Sex-Associated DNA Methylation
Cognitive and behavioral risk factors for low quality of life in survivors of childhood acute lymphoblastic leukemia
The version of record of this article, first published in Pediatric Research, is available online at Publisher’s website: http://dx.doi.org/10.1038/s41390-020-01230-7With high survival rates for pediatric acute lymphoblastic leukemia (ALL), long-term quality of life is a prominent consideration in treatment. We concurrently evaluated cognition, behavior, and quality of life in child and adolescent ALL survivors and determined associations between them.This work was supported by the Ontario Institute for Cancer Research through funding
provided by the Government of Ontario, the Canadian Institutes of Health Research (168925), and the Canadian Cancer Society (Grant #703558)
Obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: distinct associations with DNA methylation and genetic variation
Abstract
Background
A growing body of research has demonstrated associations between specific neurodevelopmental disorders and variation in DNA methylation (DNAm), implicating this molecular mark as a possible contributor to the molecular etiology of these disorders and/or as a novel disease biomarker. Furthermore, genetic risk variants of neurodevelopmental disorders have been found to be enriched at loci associated with DNAm patterns, referred to as methylation quantitative trait loci (mQTLs).
Methods
We conducted two epigenome-wide association studies in individuals with attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) (aged 4–18 years) using DNA extracted from saliva. DNAm data generated on the Illumina Human Methylation 450 K array were used to examine the interaction between genetic variation and DNAm patterns associated with these disorders.
Results
Using linear regression followed by principal component analysis, individuals with the most endorsed symptoms of ADHD or OCD were found to have significantly more distinct DNAm patterns from controls, as compared to all cases. This suggested that the phenotypic heterogeneity of these disorders is reflected in altered DNAm at specific sites. Further investigations of the DNAm sites associated with each disorder revealed that despite little overlap of these DNAm sites across the two disorders, both disorders were significantly enriched for mQTLs within our sample.
Conclusions
Our DNAm data provide insights into the regulatory changes associated with genetic variation, highlighting their potential utility both in directing GWAS and in elucidating the pathophysiology of neurodevelopmental disorders