‘Epigenetic Variations Could Underlie Neurodevelopmental Disorders, Congenital Anomalies’
“Genetics are thought to underlie many types of neurodevelopmental disorders and congenital anomalies, but for a lot of cases, genomic analysis has been unable to give answers. An international team of researchers has now suggested that instead, epigenetic changes could be involved.”
“As the researchers, led by Andrew Sharp at the Icahn School of Medicine at Mount Sinai, reported today in Nature Communications, they compared the DNA methylation profiles of nearly 500 individuals with neurodevelopmental disorders and congenital anomalies to those of about 1,500 controls. While they found that epigenetic variants — dubbed epivariations — are common in the human genome, they also discovered that de novo epivariations are more common among affected individuals than controls. They further noted that these epivariations appear to influence gene expression, which could affect disease.
“Our study suggests that these epigenetic mutations are a significant contributor to human disease,” Sharp said in a statement.”
“Epivariations could have functional consequences akin to those of loss-of-function mutations, the researchers wrote. Using RNA-seq and DNA methylation data from the 1000 Genomes Project, they found that epivariations at promoters led to large changes in gene expression: Decreased methylation resulted in increased expression, while increased methylation led to decreased expression.
Based on this, the researches argued that epivariations could contribute to disease pathogenesis in some patients and may have diagnostic relevance.
“These findings can open up a whole new world in what we know about disease and genetic profiling,” Sharp said. “Investigating DNA methylation when profiling genomes for disease mutations could help us uncover causative defects in congenital and neurodevelopmental diseases that have eluded us for years.”
https://www.genomeweb.com/epigenetic-research/epigenetic-variations-could-underlie-neurodevelopmental-disorders-congenital#.WxmsVhYpDDs