DNA hypomethylation makes humans prone to diseases
22.05.2012 - A Polish-US research team has found that hypomethylation destablises DNA and boosts the risk of neurological diseases.
Warsaw/Houston –Bioinformaticians from Warsaw University and the Baylor College of Medicine have provided an explanation for how disease-associated mutation hotspots may arise. According to results of the group under Aleksandar Milosavljevic and Tomasz Gambin, regions on human chromosomes that carry only few so-called methylation marks show a tenfold higher number of structural mutations than the genome-wide average. Patients diagnosed with schizophrenia, bipolar disorder, developmental delay, and autism had a significant higher amount of such predetermined breaking points, (PloS Genetics 8(5): e1002692).
The researchers suggest that the amount of methylation might mediate genomic stability. They compared methylome maps from human sperm cell samples with publicly available structural variation data. Their results points to a strong association of germline hypomethylation and genomic instability which might lead to new diagnostic and therapeutic approaches. "We have found that these rare and de novo structural variants, as well as changes of the human genome that have accumulated the fastest since the branching chimpanzee, are significantly concentrated within methylation deserts," senior author Aleksandar Milosavljevic, a molecular and human genetics researcher at Baylor College of Medicine, said in a statement.
Lack of methylation of genomic DNA has been previously associated with high structural mutability in gibbons and in human cancer cells, but the association with structural mutability in the human germline has not been explored prior to this study.
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