Epigenetic Diseases

Over the past few decades, the role of genetics in disease has become a topic of many research studies. However, an already complicated field has become increasingly complex with the advent of epigenetics. This relatively new field focuses on chemical alterations of the genetic material that do not alter the DNA sequence itself.

The chemical alterations that are currently known under the umbrella of epigenetics include the methylation of DNA and deacetylation of histones, the proteins around which the DNA wind to condense within the cell nucleus. The chemical alteration of nucleotides can affect gene expression by manipulating how transcription factors interact with the DNA. Alteration of the histone, and thus the condensation of the DNA, can affect the availability of the DNA for binding. Both of these cases infer alterations in the rate of gene expression.

Gene expression is a varied lot and normal levels are dependent on both the gene and the cell in which it is expressed. Aberrant expression – an “off” gene being “on” – or altered levels of expression are the basis of many cancers. The presence of mutant proteins is also the basis of diseases such as Alzheimer’s. The DNA sequence may affect gene expression through the presence of transcription factor binding sites (the rate i.e. RNA levels), or through mutations transferred to the resulting mRNA (resulting in mutant proteins or its degradation and no protein). Thus, the genome and epigenome overlap in some ways in regards to gene expression.

Recent studies of monozygotic (identical) twins have shown that identical genomes can have different epigenomes. In other words, the DNA sequence and epigenetic changes are inherited separately. The epigenome is likely the portion of our genetic inheritance affected by environmental factors. Twins sometimes develop different diseases later in life, including cardiovascular disease, which is thought to have a genetic component. If their DNA is identical, how can only one twin get the disease? The conclusion researchers are reaching is: epigenetics.

There has also been work to show that tumor suppressor genes, particularly ATM in colorectal cancer, might be turned off by aberrant DNA methylation, a form of gene silencing. This silencing would result in a lack of tumor suppression and the development of tumors. Other cancers shown to be affected by DNA methylation include breast cancer (the BRCA gene), cholangiocarcinoma, ovarian cancer, pancreatic ductal adenocarcinoma, gastric cancer, and liver cancer. Meanwhile, histone deacetylases are of interest for neuroblastoma.

Other disorders considered to be the result of epigenetics affecting gene expression are inflammatory disorders, systemic lupus erythamatosus (SLE), diseases due to X-chromosome inactivation (hemophilia, bipolar disorder, thyroid dysgenesis), and possibly schizophrenia, among others.

There are a number of unanswered questions regarding epigenetics and its role in disease, but it is emerging as the mechanism by which cellular environment affects gene expression and associated diseases.


For a list of studies used to reference cancers affected by epigenetics, search Pubmed using the words “tumor suppressor epigenetics” without the quotes there are a great number more than mentioned above.

For the twin studies see Kaminsky et al. DNA methylation profiles in monozygotic and dizygotic twins. Nature Genetics, 2009 (epub ahead of print); and Singh, Murphy, and O’Reilly. Epigenetic contributors to the discordance of monozygotic twins. Clinical Genetics, 62, 2002.

Other references are linked in the text where appropriate.