Epigenetics is all the rage. It is the study of heritable changes caused by mechanisms other than changes in the underlying DNA sequence – hence the name epigenetics, or “above the genes.” It refers to changes to the genome that do not involve changes in the base pair DNA sequence.
An example of such modifications is DNA methylation, which regulates gene expression without altering the underlying DNA sequence. When areas of the genome are methylated more heavily than others, the highly methylated areas tend to be less transcriptionally active, through a mechanism not fully understood. These heritable epigenetic changes are passed down and may last for multiple generations.
However, it is important to remember, there is no change in the underlying DNA sequence of the organism in spite of the heritability of these changes; instead, mysterious non-genetic factors cause the organism’s genes to express themselves differently.
Genetic inheritance has historically been thought of as involving the transmission of DNA from one generation to the next affected by occasional mutations in the DNA itself. A few scientists had hypothesized that the conventional genetic model was too simplistic to explain the complexity of human beings. The revelation that the active human genome likely contains only about 30,000 genes, coupled with increasing experimental evidence on the variability of identical twins, led scientists to believe that other factors allow genes to be switched on and off in response to environmental stimuli, consequences that may affect subsequent generations. Thus your genome is under your protection during your life, but may be under someone else’s possession in the future, meaning we need to care and nurture our genome.
In the early 1980s, Professor Marcus Pembrey, head of the Clinical Genetics Department at Great Ormond Street Hospital, London, often studied families exhibiting unconventional genetic inheritance patterns. He studied two genetic diseases with the same DNA mutation:
- Angelman syndrome, which displays clinical symptoms of jerky movements, little or no speech and a very happy personality.
- Prader-Willi syndrome, which patients are found to be very floppy in infancy and develop an insatiable appetite associated with obesity in later life.
He worked out that these two completely different diseases were caused by exactly the same genetic alteration, a small deletion on chromosome 15.
What was even more remarkable was that the parent from whom the mutation was inherited determined which disease was observed in the patient. If it was inherited from the mother then the child would have Angelman syndrome. If from the father, then the child would have Prader-Willi syndrome.
This phenomenon suggested that the chromosome somehow ‘knew’ its origin and therefore must be tagged or imprinted in some way – this has become known as ‘genomic imprinting‘. During sperm or egg production, a chemical change results in the same DNA sequence on each chromosome having different functional properties. These events can lead to a particular gene being turned on or off, usually by methylation, the central principle underlying ‘epigenetics’.
What roles does vitamin D deficiency play in methylation and thus epigenetics? Dr Haidong Zhu and colleagues of the Georgia Health Sciences University wanted to find out.
They studied the genes of 11 African American children with vitamin D deficiency (<10 ng/ml) comparing them to 11 age-matched controls ( > 30 ng/ml).
First, they pointed out that up to 10% of the human genome is regulated directly and indirectly by vitamin D. Genome-wide vitamin D response has a few thousand chromosomal target sites that regulate several hundred target genes.
What they found is that in three out of the four vitamin D genes they studied, there was a difference in methylation when comparing sufficient children to deficient children. They concluded,
“Severe vitamin D deficiency is associated with methylation changes in leukocyte DNA.”
In other words, it is very possible that vitamin D deficiency may directly damage your DNA. On the other hand, being sufficient in vitamin D may protect your genes and prevent epigenetic changes in the genes you pass down to your children and grandchildren and so on.