Epigenetics/Epigenomics 101

Genomics 101 was an introduction into the relationship of gene expression, the environment and disease. Like most things in life it isn’t that simple! Genes are definitely being expressed abnormally but gene mutation alone just isn’t enough to explain many of the diseases that are affecting us. The "BIG" question that is being explored is how non sequence-based alterations to our DNA are involved in disease.

This area of research called epigenetics — literally in addition to genetics — is attempting to understand all the weird and wonderful things that are not explainable by genetics alone. Epigenetics focuses on processes that regulate how and when certain genes are turned on and turned off, while epigenomics pertains to the analysis of epigenetic changes across many genes in a cell or entire organism. Historically the word epigenetic has had a broad definition but its present definition refers to heritable traits that do not involve changes to the underlying DNA sequence — non-mutation changes. While the genome is relatively fixed throughout life the epigenome is dynamic, responding to the environment as an adaptive mechanism.

Let’s try to put this all into perspective. We all start out life as single celled organisms, fertilized eggs. The genomes inside those eggs are created by combining 23 chromosomes each, with their accompanying genes, from our parents for a total of 46. Within our 20,000 or so gene pairs there are "misfits", hardwired mutations that may cause or predispose us to particular diseases.

Mutations cause genetic disorders like cystic fibrosis, sickle cell anemia and thousands other diseases that are relatively rare and account for about 2% of our disease load. They are thought to be caused by a mutation to a specific gene and follow Mendelian inheritance patterns. Polygenic conditions like cancer and heart disease are caused by a combination of environmental conditions and mutations in multiple genes. These conditions are the most chronic conditions that affect us and really account for almost all of the other 98%. (http://www.ornl.gov/).

Genetic variants that are presently generating a lot of attention are single nucleotide polymorphisms or SNPs — pronounced Snips. SNPs are single base pair differences in a gene sequence that can affect how a person responds to different pathogens, various chemicals, drugs, vaccines and other environmental factors. All common diseases are a result of gene-environment interactions and SNPs play their part. The SNP is only one player, though, in a very complex interaction of hundreds of genes, gene product interactions, environmental signaling and lifestyle factors over a lifetime starting in the womb.

Our genome is difficult to change and mutations alone cannot account for cancer, cardiovascular diseases, Alzheimer’s, obesity, diabetes or any of the other conditions that are becoming more prevalent in industrialized societies. Our genomes are really very adaptive and conserved entities that are highly interactive both within the cell and with the outside world.

As it is presently understood the epigenome consists of molecular "tags" or "marks" that can silence a fully functioning gene. In most cases this is a normal process of growth and development. But in other cases these "tags", called methyl or acetyl groups, silence genes that should be active, and contributes to disease susceptibility. Environmental factors throughout all stages of life alter the functioning of the genome. The epigenome appears to be the connection between nature and nurture that can have both positive and negative effects.http://the-scientist.com/2012/03/06/exercise-alters-epigenetics/

Summing it up we can say that all complex diseases are the result of gene-environment interactions over time. Researchers in the field of epigenetics suspect that environmental factors (chemicals, diet, drugs, stress, behavior) modulate the epigenetic process leading to altered gene expression patterns. Add those patterns to human variability and minor mutations (SNPs) and you create the individual differences we see in disease susceptibility and prescription drug sensitivity.

Like the genome the effects of the epigenome can also be measured and evaluated. Since we are talking about gene expression it doesn’t matter whether we are measuring a mutant gene or an epigenetically altered gene — gene expression is gene expression! The key to the Iris BioWindows™ system is that it measures the expression of important genes involved in a diseased tissue (nature) and then interfaces that data with lifestyle, medical, family and environmental information (nurture) to find the best medical protocol for each individual patient. For a good primer refer to Epigenetics in Nova Science.