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Epigenetics and Disease Severity

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What factors (epigenetic and otherwise) can be identified which may influence the onset/phenotype/progression/severity of inherited disease in a family sharing a specific gene variant?

Genomics
Epigenetics
Variant Calling
Variant interpretation
Rob Walsh
21 months ago

3 answers

1

The behavior of a person's genes doesn't just depend on the genes' DNA sequence - it's also affected by so-called epigenetic factors. Changes in these factors can play a critical role in disease. (Simmons, D. (2008) Epigenetic influence and disease. Nature Education 1(1):6). Epigenetics involves genetic control by factors other than an individual's DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed. Epigenetics is involved in many normal cellular processes. Consider the fact that our cells all have the same DNA, but our bodies contain many different types of cells: neurons, liver cells, pancreatic cells, inflammatory cells, and others (Egger, G., et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 457–463 (2004)). 

Factors!

  • DNA Methylation
  • Histone Modifications
  • RNA-Associated Silencing


Epigenetic marks in an organism can be altered by environmental factors throughout life. Although changes in the epigenetic code can be positive, some are associated with severe diseases, in particular, cancer and neuropsychiatric disorders. Recent evidence has indicated that certain epigenetic marks can be inherited, and reshape developmental and cellular features over generations. (Neuropsychopharmacology. 2013;38(1):220-36).

Samares B
21 months ago
0

Why are you interested in epigenetic factors, rather than genetic ones?
It would be straightforward to, for example, collect blood from both affected and unaffected individuals in a family, and measure epigenetic marks, such as DNA methylation or histone marks. You could then do a comparison across the genome to see if there are strong differences at some genomic positions between affected an unaffected family members. However, the key problem of epigenome-wide association studies is that in general you can't know if the differences are the *cause* of differences in onset/phenotype/severity or are the *consequence* of these. The same is not true for genetic differences, because (except for cancer) they cannot be present as a consequence of the disease process, only possibly as a cause.

Jeremy Schwartzentruber
21 months ago
0

Epigenetics involves genetic control by factors other than an individual's DNA sequence. Epigenetic changes can switch genes on or off and determine which proteins are transcribed.
Epigenetics is involved in many normal cellular processes. Consider the fact that our cells all have the same DNA, but our bodies contain many different types of cells: neurons, liver cells, pancreatic cells, inflammatory cells, and others. How can this be? In short, cells, tissues, and organs differ because they have certain sets of genes that are "turned on" or expressed, as well as other sets that are "turned off" or inhibited. Epigenetic silencing is one way to turn genes off, and it can contribute to differential expression. Silencing might also explain, in part, why genetic twins are not phenotypically identical. In addition, epigenetics is important for X-chromosome inactivation in female mammals, which is necessary so that females do not have twice the number of X-chromosome gene products as males (Egger et al., 2004). Thus, the significance of turning genes off via epigenetic changes is readily apparent.

While epigenetic changes are required for normal development and health, they can also be responsible for some disease states. Disrupting any of the three systems that contribute to epigenetic alterations can cause abnormal activation or silencing of genes. Such disruptions have been associated with cancer, syndromes involving chromosomal instabilities, and mental retardation.

Factors are DNA Methylation, Histone Modifications and RNA Associated Silencing.

Egger, G. et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 460 (2004). 

Abhishek Raj
21 months ago

Have some input?