By: Dr. Shanna Ndong The analogy I often use for genetics is that DNA is the cookbook for the human body, residing inside the nucleus of every cell. RNA transcribes the genes (recipes) to make whatever proteins the cell needs. The human genome contains approximately 20,000 genes. DNA is made up of billions of repeating nucleotide molecules and is organized and condensed with proteins into chromosomes in the nucleus in preparation for cell division. This article is the first in a three-part series that explores the exciting and rapidly evolving field of epigenetics. Epigenetics is the study of inherited processes that can alter gene expression. In the 1970s, it was discovered that mechanisms other than the DNA sequence itself are important in determining the expression of genetic traits and can be passed to offspring. DNA methylation and acetylation are two such mechanisms. Methyl groups can become permanently attached to cytosine, one of the chemical bases in DNA, and can replicate with it through generations. The attachment of methyl groups significantly alters the gene it binds, inhibiting its transcription. Other molecules, called acetyl groups, were found to play the opposite role, unwinding DNA and making it easier for RNA to transcribe a given gene. An important concept to mention when discussing epigenetics is genomic imprinting. We inherit two working copies of most genes, (one from each parent) but with imprinted genes, we utilize only one working copy. Depending on the gene, either the copy from mom or the copy from dad is epigenetically silenced through the addition of methyl groups during egg or sperm formation. Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. In many cases, UPD has no effect on health or development because most genes are not imprinted. However, one of several genetic disorders can result from UPD if imprinted genes are involved. The most well-known conditions include Prader-Willi syndrome, which is characterized by uncontrolled eating and obesity, and Angelman syndrome, which causes intellectual disability and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. A number of important conditions may result from external or environmental factors. It is now well accepted that conditions in the womb can determine later risk for a number of diseases through epigenetic mechanisms, including obesity, diabetes, allergies, asthma, and heart disease. The mother’s nutrition, including vitamin levels (particularly folate, B vitamins, and choline) and blood glucose, as well as mental health and substance abuse history, have all been shown to influence the methylation patterns of key genes in her offspring. Since DNA methylation is a common mechanism for inactivation of genes, diets high in methyl-donating nutrients may help to alter gene expression, particularly during early development. A mother’s diet during pregnancy (and conception) and an infant’s diet can affect the epigenome (and health) in long-lasting ways. Diets that are rich in folate and choline are essential during these periods. In adulthood, too little of these nutrients can result in hypermethylation, but it is typically reversible with changes in diet. A number of dietary supplements are of particular interest in the field of epigenetics. Many of these compounds display anticancer properties and may play a role in cancer prevention. I will discuss this topic further in the next article in this series (The Epigenetic Diet and Cancer). Heavy metals are widespread environmental contaminants and have been associated with a number of diseases, such as cancer, cardiovascular diseases, neurological disorders and autoimmune diseases. Several studies have established an association between DNA methylation and environmental metals, including arsenic, nickel, and cadmium. Various other environmental pollutants that have been linked to disease through epigenetic mechanisms include pesticides (testes and ovarian dysfunction), air pollution (heart and lung disease), and bisphenol A, BPA: hormone disruptor (increased cancer risk). There is strong evidence that experiences can cause epigenetic changes and that psychological and behavioral tendencies are inherited. A parent’s or grandparent’s exposure to emotional trauma may not only impact their mental health, but animal studies have shown changes in methylation patterns in the brains of their children and grandchildren. This field of research is called behavioral epigenetics, and it will be the subject of the third article in this series. By: Dr. Shanna Ndong

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