Multiple Sclerosis in Twins

How can one identical twin develop multiple sclerosis while another does not?

Multiple sclerosis is a debilitating neuroimmunological and neurodegenerative disease affecting more than 400,000 individuals in the United States and more than 1.3 million worldwide. In collaboration with Dr. Stephen Hauser's group at the University of California, San Francisco, and funded by Small Ventures USA and the AJ Brass Foundation, NCGR scientists have been sequencing the genomes of identical (monozygotic) twins that are discordant for multiple sclerosis (MS). There is a strong genetic susceptibility component involved in contracting MS. In identical twins in which one twin has MS, there is a 2 in 3 chance that the other twin will also be affected. By comparing the DNA code of identical twins who are discordant for MS, NCGR scientists are looking for clues to explain why not all identical twins are affected by this disease. For the first time ever, NCGR scientists are examining both the genome sequence and the sequence of the part of the genome that is expressed (mRNA sequencing) in T lymphocytes, which are important in causing disease, and the sequence of the epigenome (or DNA methylome). DNA methylation is the only flexible genomic parameter that can change genome function under external influence. Hence it constitutes the main, and, so far, missing link between genetics, disease and the environment that is widely believed to play a decisive role in the cause of virtually all human diseases. The results of these studies were reported at the American Society of Human Genetics Conference in October 2009 and will soon be in a leading scientific journal.