Sunday, 15 August 2010

MS and Twins

Twin studies were first proposed over a century ago to separate the relative contributions of nature (genes) and nurture (the environment) in determining a trait/disease. Higher concordance (where both twin pairs are affected) rates between genetically identical (monozygotic, MZ) twins versus non identical (dizygotic, DZ) twins provides evidence for genetic factors determining a disease. In MS, about 30% of MZ twins are concordant as compared to about 5% of DZ twins. More MZ twins being concordant as compared to DZ, suggests that genes are involved in MS, but the fact that MZ twins are not 100% concordant means that the environment also plays a role in the cause of MS.

However, given that the average adult has billions of cells and that when DNA is copied between these cells errors can arise, differences in the DNA sequence of MZ twins have been reported. Furthermore, a relatively new field of genetics, called epigenetics, which refers to modifications of DNA that regulate the function of the genome, has also been shown to differ between MZ twins. MZ twins discordant for a disease could actually therefore be explained by genetic or epigenetic differences between twins, but until recently this has not been examined in detail.

Baranzini and colleagues sequenced the genome and epigenome from one pair of MZ twins discordant for MS (http://www.nature.com/nature/journal/v464/n7293/full/nature08990.html). Given that the sequence of the first human genome that was released in 2000 represented 15 years of work and $3 billion. This work represents the future of genetic research as technology has vastly improved meaning that a whole genome can be sequenced in 1 week for $10,000.

So what was found? Comparison of the entire genome and some regions of the epigenome did not find any reproducible difference in DNA sequence between twins, suggesting that as previously thought, the environment plays the most significant role in determining twin concordance for MS.

However, genetic and epigenetic differences between twins are not completely ruled out by this study. Whilst the paper represents a huge effort, there are a number of limitations including the fact that only 3% of the epigenome was investigated. The epidemiology of MS (e.g. more females being affected) implies that epigenetics will be important in the cause of the disease and more work is needed to work out which factors are involved.

Watch this space.

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