Genetics

Question 1

What dietary factors influence DNA?

Answer 1

Many vitamins and minerals are cofactors for enzymes or are structurally important within proteins involved in:

• DNA synthesis and repair e.g. B vitamins and iron
• Prevention of oxidative damage to DNA e.g. vitamin C, E and other antioxidants (deficiency = increased DNA strand and chromosome breaks)
• Maintenance methylation of DNA e.g. folate, vit B12 (deficiency = increased chromosome breaks and DNA hypromethylation)

Question 2

What is DNA methylation?

Answer 2

Methylation occurs on CpG sites (cytosine followed by a phosphate followed by a guanine) which are common in gene promoter regions so methylation has an effect on whether or not that gene is subsequently read or not.

• A methyl group is attached to the cytosine base by a methyltransferase enzyme which causes the gene to not be expressed (turns off the gene). It inhibits the transcription of genes in two ways:
  1. prevents the binding of transcription factors to the DNA
  2. attracting proteins that condense the DNA-histones complex making the DNA inaccessible to transcription factors.

Question 3

What dietary factors can cause a lack of methylation? What are the effects?

Answer 3

The methyl groups are provided by the diet.
Deficiency of dietary methyl donors e.g. folate, vit B12, choline

• Dysregulation of DNA methylation pattern is a central feature of carcinogenic processes.
• Cancer cells have less methylation and so have more active DNA than healthy cells.

Question 4

Define Nutrigenetics, nutrigenomics and epigenetics

Answer 4

Nutrigenetics - the effect of genetic variation on dietary response
Nutrigenomics - the role of nutrients and bioactive food compounds in gene expression
Epigenetics - the heritable transmission of phenotype without a change in the underlying DNA sequence.

Question 5

Discuss the effects of exercise on DNA

Answer 5

Bad:

• Exercise increases the production of reactive oxygen species because you need to produce more energy. The production of free radicals enhances the activation of several transcription factors.
• free radicals can cause cellular damage
• Mitochondrial DNA at risk of damage caused by free radicals (reactive oxygen specis). In the electron respiratory chain (to produce ATP) there is leakage of electrons so some electrons go into the intermembral space and combine with oxygen to form reactive oxygen species.
• superoxide radical (SOD) - hydrogen peroxide - GPX, PRX - water and oxygen (antioxidant enzymes), so antioxidants can reduce the damage caused by free radicals
• Hypermethylates genes of the adipose tissues which can reduce our capacity to store free fatty acids.

Good:
- Increased number of mitochondria - a lot of conditions e.g. obesity and some cancers are related mitochondria disfunction and exercise is a good way to reverse this.

• Methylation inhibits gene expression. Exercise reduces methylation. PGC-1(alpha) stimulates the synthesis of mitochondria proteins increasing the number of mitochondria in the cell. If you have the gene methylated you will have reduced mitochondrial synthesis. This reponse relies on stimulus: intensity, duration, frequency.
• Hypomethylates skeletal muscle genes

-Telomeres - can increase the length of telomeres (at the end of chromosomes to protect them from degradation) and this can expand cell life