A recent study published in the April 28th issue of Nature is befuddling to those looking for answers about multiple sclerosis (MS) on the genetic level.
Scientists recruited three pairs of MS discordant identical twins (one of each pair had MS and one did not) to provide samples of DNA. The researchers then sequenced the entire genome for each of the participants - 2.8 billion "base pairs" for each one, to be exact - and compared the twins' DNA to one another.
Guess what they found? No difference in the DNA. None at all.
The scientists even conducted a very detailed investigation of immune cells, as MS is though by most experts to be an autoimmune disease, basically sequencing those and looking for differences. Still, no differences.
Although it would be tempting to say that this study (which cost 1.5 million dollars and took 18 months to complete the sequencing) provided no information, the fact is that it did tell us something - that there is apparently no direct genetic cause of MS. Otherwise, there would have been a difference in the DNA between the twins.
This doesn't mean that genetics doesn't play a role in MS, however. It could be a situation where there is a genetic component that is "necessary, but not sufficient" and requires an environmental factor to start the process that leads to MS, like an infection that one twin was exposed to and the other wasn't.
It is estimated that the likelihood of an identical twin developing MS if the other twin has MS is 30%. This falls to 4% likelihood in a non-identical twin and less than 3% in a non-twin sibling.
This is the first time that the entire genome of twins with autoimmune disease has been sequenced.
Source: Sergio E. Baranzini, Joann Mudge, Jennifer C. van Velkinburgh, et al. "Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis." Nature 464, 1351-1356 (29 April 2010).
Nicely put!
This is extremely interesting! I always tease my parents that one of the reasons I have MS (I’m the only one in our family) is because they, two completely different, polar-opposite people, came together to form the right genetic profile that is me. (This is in jest, of course – but the fact that I can’t imagine how they ever ended up together adds to the uniqueness of the fun.) Now it seems my genetics may not hold the answers. I guess I will try putting the blame on that “imaginary” boy who exposed me to the kissing disease, Mono, at age 15. He’s imaginary because I really did not kiss anyone – that I can remember. But it appears maybe my MS is environmentally caused – so I must now blame that kissing boy! (And further environmental factors – my mother’s awesome cooking?? Can’t blame diet sodas – never drank ‘em!)
Thanks for the information! We need more study in the area of genetics and MS. When my mother was diagnosed with MS in 1979 she was told it was not genetic. Since then opinion has gone back and forth it seems. And when not one but two of my sisters were diagnosed in the 1990′s, our family seemed to feel there must be a genetic link. Now I’m the fourth to be diagnosed in our family. So much for probabilities. We all worry for the next generation.
I have MS and so does my sister, and she is adopted. I have always joked that it was the load of topsoil my folks got when we were small. We also live near Seattle, which is an area that has a very high incidence of MS. No genetic relationship to each other in this case, but definitely an environmental one.
This is very interesting. I have MS and so does my step-sister, but unlike the adopted sister we didn’t live in the same household until we were in our teens. It is my understanding that Wisconsin has a high incidence of MS (like Seattle) and both of us were raised in northern wisconsin (in separate citiies) and live in wisconsin to this day. She is particularly worried about passing MS on to her girls as her mother also has MS. I am the first MS diagnosis in my family but have watched my children like hawks for signs of MS but feel like I’ll be able to relax my vigil now.
“…but did only one of the twins have CCSVI? After all, if CCSVI is a congenital (inherited) trait, wouldn’t we expect it in identical twins?”
Not necessarily! Genes IDENTICAL with a minute mitochondrial error can affect the way individual cells are expressed. Mitochondrial DNA is less than 1/300,000th of the total length of nuclear DNA sequence within the gene.
On fertilization each egg contains more than 1,000 mitochondria, each with its own DNA. This means that several mitochondrial genotypes may exist side-by-side in the egg. MtDNA control the way other genes contained in the nuclear genome behave, especially autoimmune cells.
There are over 4,000 well-known MtDNA illnesses. It is my opinion that MS is one of them.
Take a look at my link here about a study that shows the connection genetically! People with MS have a chromosome in common 6p21.32 venous disease.
No Link Denise!
It’s good to know what DOESN’T cause MS, although it’d be an easy answer if genetics were to blame.
It is a basic premise of quantitative genetics that the phenotype is a product of both genomic capacity and environmental stimuli. Epigenetics provides the key to understanding the environmental component, i.e. which genes are ‘switched on’ at any given time. Studies of Heightened Immune Response (HIR) syndrome provide some interesting parallels with MS, e.g. the majority of those afflicted are women who are nearing the end of their reproductive peak, which appears to trigger the onset of deleterious effects. This has been postulated to be an advantageous fecundity trait, i.e. the deleterious effects of an overactive immune system are ‘staved off’ until the offspring have been born. There is a significant ‘cluster’ for HIR around Glasgow, Scotland, where, it has been proposed, an ‘environmental trigger’ for heightened immunity may be abundant.
I am one of 3 females, within a year of each other, who went to the same college, lived in the same dormitory and were in the college of nursing, who are diagnosed with MS. There may be others, but we have never investigated this occurrence. The most common link in our nursing careers is that we all did long term care, either with adults or children. We all live in the Chicago area, which is known to have a high incidence of MS. We have not compared our lives to see if there are other factors that may be similar. We are also the first ones in our families diagnosed with MS. Instead of genetic factors ‘causing’ MS, I would love for researchers to look at the genetic similarities of people diagnosed with MS to see if we have a genetic factor that may be triggered by external factors. The external factors could be a multitude of categories, but maybe a focus in environmental exposures may point to something. Or a similar factor in people who are diagnosed with MS. My MS physician told me, in one of our initial consultations, that the majority of his patients are nurses. Let’s look!