Epigenetics and Disease

Because epigenetic tags decide which genes are switched on or off, abnormal epigenetic changes can cause disease. A gene that should be active may be silenced, or a gene that should be silent may be switched on. The DNA base sequence is normal, but the gene is expressed at the wrong time, in the wrong cells, or not at all.Epigenetic changes can be triggered by environmental factors such as smoking, diet, stress and pollutants, and they build up with age. Unlike mutations, they are potentially reversible.Example: fragile X syndrome. In fragile X syndrome, a repeated section of DNA in the FMR1 gene becomes much longer than normal and is heavily methylated. The increased methylation silences the gene, so its protein, which is needed for normal brain development, is not made. This causes learning difficulties.Example: cancer. Abnormal methylation and acetylation can switch off genes that normally slow cell division, or switch on genes that stimulate it, leading to tumours. This is covered in later lessons.Relevance to diagnosis and treatment
• Abnormal methylation patterns can be detected in samples of DNA, even DNA in blood, helping to diagnose disease early.
• Because epigenetic changes are reversible, drugs can be designed to reverse them, for example by inhibiting the enzymes that add methyl groups or remove acetyl groups.
• Such drugs must be specific, because the same enzymes act in healthy cells too.Epigenetics can also help explain why people with the same genotype, such as identical twins, may differ in whether they develop a disease.