Snapshot: What is Polyglutamine Expansion?

The information that allows the normal development and functioning of each human being is coded in DNA, which exists in all cells of the body. Several successive segments of DNA make up a gene, with the human body containing approximately 20,000. Every gene has a different arrangement of DNA segments and itself codes for a protein with a specific function. Genes code for proteins in the sequence of their DNA: combination of DNA sequences “code” for different protein precursors called amino acids. Thus, information from DNA (“genes”) codes for amino acids, which come together to form proteins, who function to maintain the normal well-being of the body.

A small number of genes have a small segment of DNA that is repeated successively, usually a couple dozen times, for unknown reasons. When the respective protein is formed, it also possesses a repetition of the same amino acid, corresponding to the repeated DNA segment. These repetitions in proteins have the prefix “poly”, meaning that the amino acids are repeated multiple times in a row, causing an “expansion” in the protein. One of the most common repeated amino acids is called glutamine: hence the name, polyglutamine.

Diagram showing how multiple CAG triplet repeats code for replicates of glutamine to be inserted into a protein
Photo courtesy of NHS HEE Genomics Education Programme.

When there is an increase in the number of repetitions of these segments in DNA, we say that an expansion of the polyglutamine has occurred. When the number of glutamines is increased sufficiently, a disease can develop: we call these disorders “polyglutamine diseases”. Some examples of diseases caused by this polyglutamine expansion are Huntington’s disease, SCA1, SCA2, SCA3, SCA6, and SCA7. The difference between all these diseases is that the expansion of the DNA segment that causes the polyglutamine occurs in different genes. Since these genes are distinct, the way that this expansion interferes with the normal body functioning is also different, giving rise to altered clinical presentations and courses. Moreover, it has been well established that, the larger the number of times that the segment is repeated, the more severe the disease will be. Finally, it has also been observed that throughout each generation, abnormally increased segments tend to become even bigger, making the disease worse.

The discovery of this mechanism of disease has been very important for scientists, since it allows for a “molecular diagnosis” of the disease. Armed with this understanding, research is now focused on understanding this process and finding ways to block the negative effects of polyglutamine expansion.

If you would like to learn more about polyglutamine expansion, take a look at this article.

Snapshot written by Jorge Diogo Da Silva, edited by Dr. Maxime Rousseaux

 

 

Snapshot: What is DNA?

DNA (deoxyribonucleic acid) is the way that living beings store the information that determines how they look and function. Think about DNA as the blueprints, or instructions, for life. All life forms – humans, cats, dogs, trees, and bacteria – all contain DNA. Your DNA is what carries the information that decides your specific traits, like what color eyes you have or if you will be tall or short. All the information in your DNA is unique to you. No one else in the world has the exact same DNA as you, unless you have an identical twin. You do share about fifty percent of your DNA with your biological parents, because the information stored in DNA is transmitted from generation to generation. This is why you look a little bit or a lot like your parents.

The reason that traits, like having blue eyes or being short, run in families is because they are transmitted in genes, which are the functional units of DNA.  Genes work on a very small scale, providing instructions to the cells of your body so they know what they need to make to do their jobs. While normal changes in the DNA can influence physical characteristics, like eye color, sometimes abnormal changes in the DNA may cause individuals to develop a disease. This is the case for hereditary ataxias. The abnormal DNA changes (called “mutations”) make it so cells no longer do their jobs well. Although we live with the same DNA information all our lives, it may take years or decades for a disease to manifest. As with genes for eye color, the genes causing a disease can be transmitted across generations. This explains why families are more likely to have relatives with the same type of ataxia.

Cartoon drawing of DNA moleculue next to an image of a ladder
Cartoon of DNA (Left), Photo of a ladder (right)

So, that is what DNA does, but what does it actually look like? DNA forms a double helix, think of it as a twisted ladder. The sides of the DNA ladder are made up of sugars, specifically “deoxyribose” units, and phosphate groups, and the rungs of the ladder are made up of bases. There are four bases, adenine, thymine, guanine, and cytosine, or A, T, C, and G for short. In the DNA ladder, each rung is made up of two bases forming a pair, either A and T or C and G. The instructions for life are “written” into our DNA using these bases, sometimes called the “genetic code”. The language of the genetic code has a lot fewer letters than our alphabet, just A, T, C, and G, but together these four bases write every instruction for every function and characteristic of every living thing that has ever existed in the form of genes.

If you would like to learn more about DNA, take a look at this BBC article.

Snapshot written by Dr. Laura Bowie, edited by Dr. Judit M Perez Ortiz.