Overview of Genetics and Epigenetics
Genetics refers to the study of genes, which make up our genetic material (DNA). Each gene is a set of instructions (code) to make a protein that performs specific functions in the body. Changes to a genes code are called mutations. Mutations can prevent a protein from functioning correctly, thus causing a genetic disorder or medical condition.
Although every cell has a complete set of genes, only some genes are used, or expressed. Genes can be switched on or off, causing one cell to be a brain cell and another to be a bone cell. In cells, the DNA is wound around histones, and together, the DNA and histones are called chromatin. Chemical groups on the DNA and histones are called chromatin marks. Chromatin marks switch genes on and off. Some chromatin marks switch genes off by tightening the DNA around histones; other chromatin marks switch genes on by loosening it. These changes are epigenetic as opposed to genetic because the DNA code is not changed. Epigenetic changes can cause medical conditions by changing how genes are used and whether they are turned on or off correctly.
Two types of epigenetic disorders are imprinting disorders and Mendelian disorders of the epigenetic machinery (MDEMs). Imprinting disorders result directly from disrupted epigenetic or chromatin marks. An example of an imprinting disorder is Beckwith-Wiedemann syndrome. This is different from genetic mutations (described above) that cause medical conditions by changing the DNA code. Sometimes, genetic mutations can indirectly disrupt epigenetic or chromatin marks if the mutations affect genes that determine these marks. These genes are called epigenetic machinery genes, and mutations in these genes cause MDEMs. Examples of MDEMs are Kabuki syndrome and Sotos syndrome. Experts in our multidisciplinary Epigenetics and Chromatin Clinic help diagnose and develop treatment plans for people with both types of epigenetic disorders.
An Analogy for Genetics and Epigenetics
A helpful comparison is to think of the DNA sequence as the letters that form words in a book. The book represents the genome (all the DNA). Each word in the book represents a gene. Some epigenetic marks highlight words that should be read (the genes that should be turned on) at a given time. Other epigenetic marks strike through words that should not be read (genes that should be turned off) at a given time. Abnormal epigenetic marks are like highlighting or striking through the wrong word(s). Genetic mutations are like misspellings of a word. In all cases, the meaning of the words in the book is altered. This has negative consequences in the form of medical conditions. The medical conditions can be divided into two groups. The first group results from abnormal epigenetic marks (highlighting or striking through the wrong words). The second group results from mutations in the DNA code (misspelling a word).
Fahrner JA, Bjornsson HT. Mendelian disorders of the epigenetic machinery: postnatal malleability and therapeutic prospects. Hum Mol Genet. 2019 Nov 21;28(R2):R254-R264. doi: 10.1093/hmg/ddz174. PMID: 31595951; PMCID: PMC6872430. DOI: 10.1093/hmg/ddz174
Fahrner JA, Bjornsson HT. Mendelian disorders of the epigenetic machinery: tipping the balance of chromatin states. Annu Rev Genomics Hum Genet. 2014;15:269-93. PMID: 25184531; PMCID: PMC4406255. 10.1146/annurev-genom-090613-094245
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