Scientists from the University of Oxford have set up ‘Families for the Treatment of Hereditary MND’ (FaTHoM), an initiative to bring together the community of families affected by inherited forms of MND. Their first meeting will take place in Oxford on Tuesday 18th April.
Most people living with MND cannot identify a relative who has also had the condition. However, around 5% of people with MND will have a family history of the disease, which is known as inherited or familial MND. This happens when a single faulty gene is passed down from parents to their children across number of generations.
During the early stages of MND it is proposed that motor neurones are more susceptible to an imbalance of oxygen within the cells, known as oxidative stress. Prof Dame Kay Davies, at the University of Oxford, has previously shown that increasing the levels of the gene Oxr1 can protect motor neurones from death caused by oxidative stress and delay MND in mice. You can read about this work here.Read More »
The 24th International Symposium on ALS/MND began in Milan today with a record number of over 950 delegates attending to hear the latest news in MND research.
Inherited MND is a rare form of MND characterised by a family history of the disease. Over recent years more and more genes have been discovered, which has lead to an increase in individuals wishing to pursue genetic testing.
A genetic test consists of a sample, which is then sent off to a genetic laboratory. Here the blood sample is then screened for the MND-causing genes.
The gene that is faulty in inherited MND can differ between one affected family and another. Mistakes in genes called SOD1, TARD-BP, FUS and C9ORF72 between them account for about 65 – 70% of cases of inherited MND. Scientists have yet to identify the gene defects that cause the remaining 30%.
Each and every one of us is made up of thousands of different ingredients, which all combine together to create something amazing; life. Perhaps the most important of these are proteins.
Each protein in the body has its own special job to do. From making our muscles contract to controlling blood sugar, proteins are an essential ingredient in life.
In MND research we have identified a number of MND causing genes. These are genes that are found to be mutated in some people living with MND, which somehow causes the motor neurones to die. But, how does this happen? How does a gene form a protein? This blog post explains how an MND causing gene becomes a protein.
As simple as baking a cake
Here at the MND Association we love our cake. So, I thought what better way is there to describe how we make proteins?
Every cell in our body contains 23 pairs of chromosomes (46 in total), except for the egg and sperm cells that contain 23 chromosomes each.
Like a recipe book, these chromosomes hold all of our genetic material in the form of genes, in which everyone inherits two sets of (one from each parent).
Humans have approximately 24,000 genes, which each consist of their own DNA recipe to make a protein. Like cakes, proteins come in a range of different shapes and sizes, that come together to create you and me.
These DNA recipes are read by different cells to create the right protein for the job. For example, you would only make a wedding cake for a wedding, and the type of cake (chocolate or fruit) would depend on the wedding couple.
This is what happens in nerve cells (or motor neurones). A motor neurone will make a specific type of protein to help it grow, or to help it survive in low oxygen levels.
Following the recipe
A nerve cell creates a protein by finding the exact DNA recipe amongst the genes within the cell’s control centre, known as the nucleus. Once the recipe has been found the cell has a problem… The nucleus does not have the right tools to make a protein! The cell instead needs a specialised machine, or food mixer, which is only found outside of the nucleus called a ribosome.
In order to make the protein the DNA recipe needs to travel from the nucleus to the ribosome and this is done by means of a messenger. The DNA recipe can’t leave the nucleus so the cell ‘copies’ it into a messenger version, called mRNA.
The cell does this by removing certain parts of the DNA that do not affect the finished protein which are known as introns or ‘non-coding DNA’. This is known as ‘RNA splicing’ and is the same as removing raisons from a fruit cake. The cake is still made and still contains fruit, but the raisons are not essential in the finished cake.
mRNA can then travel the DNA recipe safely from the nucleus to the ribosome, where it can be finally made into a protein. Once made, this protein can then go on to do its specific job role (or in cake terms, be a wedding cake!).
Changing and ruining the recipe
Sometimes the DNA recipe in our genes can change through means of a mutation. Most of these are harmless spelling mistakes (sugarr instead of sugar) that do not affect the finished protein. However, sometimes these mutations can be so big and harmful (salt instead of sugar) that they do.
These kind of mutations are so big that the size, shape and structure of the protein can be changed – meaning that the protein can no longer do the job it was designed to do (our wedding cake is now no longer sweet and tasty, but ruined and salty!)
This is what happens in some of the MND causing genes. A big mutation occurs in the DNA recipe in a specific gene that causes the structure and shape of that protein to change. This change can then cause the proteins to ‘clump’ together in the motor neurones as they can no longer do the job they were designed to do.
An understanding of genes and how proteins are connected is essential for understanding how they can go wrong in MND. The Association funds a number of exciting research projects investigating the MND causing genes, along with the proteins they form.
To help raise awareness of MND you can bake your own cake as part of our ‘Bake it!’ fundraising campaign. For more information and to request a fundraising pack please see our website.