From osteoarthritis to a rare, fatal cancer: the mysterious elements behind the human genome | Bryan K Stinson

Leading scientists say they are witnessing a rapid increase in the rate at which people are being diagnosed with rare, potentially lethal conditions linked to rare mutations. The scientists have uncovered some of the genetic changes associated with the conditions, which include multiple sclerosis and a rare form of cancer.

The condition that causes multiple sclerosis, for example, is an autoimmune disease in which the body’s immune system attacks its own cells. If too many T-cells are activated, the body’s central nervous system can be damaged or destroyed. The rare neuromuscular condition, “omni-mutations”, also commonly causes nerve damage, can be fatal in some cases and occurs in around one in every 100,000 people.

Some mutations, whether caused by large numbers of “normal” T-cells being hijacked by the immune system or by genetic mutations, can be life-threatening. If you go out and run several miles, you will have a nice cardiovascular workout, but it won’t benefit your life expectancy one iota. For people with rare “omni-mutations” who also have heart problems, for example, it does have a modest benefit on death rates.

There is a rapid increase in the proportion of diagnoses of rare, potentially lethal conditions

The people who undergo gene sequencing to help diagnose their condition are typically drawn from a genetically similar group of around 50,000 people in the UK. The chance of a common-or-garden case, of the standard or ordinary genetic “knockout” variation that is harmless for most people, is around one in 2,000 to 3,000. But for what is sometimes known as “hypothalamic” mutations, the odds are as high as 50 in 100,000. And for the rare MALT mutations that affect people’s zinc metabolism, it’s up to 60 in 100,000.

Overall, these genetic mutations account for between 2% and 15% of all cases of multiple sclerosis and have been found in 12% of cases of anaemia. If two people are equally diagnosed with the condition, one is likely to be more likely to have a variant that affects a key molecule called a B lymphocyte, which allows the immune system to attack cancer cells. By contrast, a single B lymphocyte mutation is not enough to kill a tumour or even to cause immune system responses against other types of cancer. Nevertheless, researchers have found the right or rare variant in several of the cases they have studied.

However, they have found a time lag between when the rare mutation is caused by a mutation in the human gene for genes called histones and when it can be detected in a “genetic” blood test for multiple sclerosis and other multiple sclerosis-type conditions. The delay is usually within a few months, but as time goes on it is getting longer. It may be because there are so many good alternative testing options and people may want to wait for a less severe variant, or because the rare version of the condition is not known to cause other diseases such as multiple sclerosis. Some rare multiple sclerosis disorders are associated with low levels of a molecule that is important for inflammation. This may also be linked to low levels of histones. In any case, the risk that you will get ill with a rare illness increases as you get older. While the rare conditions come with risks, at least you can look for them, which is not so the case with the expected parts of our body that seem to be mostly unaffected by DNA.

And finally, this mutation caused an incredibly rare infection that was almost lost to science. However, because it is so weird and special, research picked it up. Nobody actually thought to test for it. In 1876, a year after Captain Cook and his crew landed in Australia, Michael Scilly of St Ives and his family were in Port Jackson, 200 miles to the north. While looking for fresh fish, Scilly was bitten by what he thought was an octopus. But he couldn’t prove that it was one – the octopus had died. Scilly was in great pain, but he managed to treat the injury by fishing and catching a moorhen.

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