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.



Where Should We Look to Detect SCA3 Pathology and Progression?

Written by Jorge Diogo Da Silva Edited by Dr. Maria do Carmo Costa

Potential drug targets and biomarkers of SCA3/MJD revealed

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is a debilitating neurodegenerative disease that usually begins in mid-life. The mutation that causes SCA3 leads to the production of an abnormally large stretch in the gene’s encoded protein, ataxin-3. This irregular ataxin-3 becomes dysfunctional and starts to bundle into toxic aggregates in the brain. SCA3 patients experience a lack of movement coordination, especially when it comes to maintaining their balance while standing or walking, which worsens over time. Currently, there is no cure, effective preventive treatment, or method of monitoring the progression of SCA3. While finding a treatment for SCA3 is undoubtedly needed, identifying markers that are only present in individuals that carry the SCA3 mutation is also critical – it allows researchers and clinicians to track how the disease is progressing, even if the carriers do not show disease symptoms. The use of disease markers is especially important in evaluating the effectiveness of a therapeutic agent during the course of a clinical trial (in this case, one that includes pre-symptomatic carriers).

Textbook diagram of brain
Diagram of the human brain. Picture courtesy of Internet Archive Book Images

The protein ataxin-3 plays many roles in cells, including in transcription – the process by which genes (made of DNA) are transformed into RNA, which in turn encodes all the proteins that are essential to maintaining normal body function. Because the abnormally large ataxin-3 is somehow dysfunctional in SCA3, accurate transcription of genes could be affected. Hence, the authors of this study have looked at transcription in several brain regions in a mouse model of SCA3. These mice harbor the human mutant ataxin-3 gene in their DNA and replicate some of the symptoms that patients experience. In general, this kind of investigation can help provide clues for potential therapeutic strategies, which could work by normalizing the transcription of disease-affected genes. In addition, it can allow researchers to better characterize SCA3-affected genes, which could be used to monitor disease progression if one or more of these genes are affected differently at different stages of the disease. The authors also searched for potential dysregulation of other molecules in the blood of these mice, such as sugars and fats, which is another way disease progression could be monitored. This is particularly useful for patients, as a blood test is much less invasive than any kind of brain analysis. Here, researchers tested blood samples of mice at different ages, as well as brain samples from 17.5-month-old mice (roughly equivalent to a 50-year-old human).

Continue reading “Where Should We Look to Detect SCA3 Pathology and Progression?”

Snapshot: What are Purkinje cells?

Purkinje cells are important neuronal cells located in the outer layers of the cerebellum. The cerebellum is part of the brain that is primarily known for controlling sense of balance and movement but can also influence learning, memory, and mood.

Purkinje cells receive lots of information from other neurons through their large and highly branched processes called dendrites (Figure 1, see below). This information is processed in large oval cell bodies of Purkinje neurons and is transmitted from Purkinje neurons through their axons, another type of neuronal process, to other neurons residing deep within the cerebellum.

Left, drawing of purkinje neuron. Right, image of a tree
Figure 1. Drawing of Purkinje cell by Spanish scientist Ramon y Cajal illustrating large and beautiful dendrites (bottom of dendrite labeled with d, top labeled by arrow) and axon (labeled with a). Information flows from top to bottom in this image, where Purkinje neurons receive input in the dendrites, process it in the cell body, and transmit it to other neurons through the axon (a). Photo of tree is on the right for comparison.

Purkinje cells look a lot like trees. The dendrites are like the leaves and branches, the cell body is like the tree trunk, and the axon is like the roots. Information starts at the top and goes to the bottom. This information processing ensures balance and accuracy of movements.

Because of these important roles, dysfunction or loss of Purkinje cells often leads to problems with balance and movement. Indeed, a loss of normal Purkinje neuron function appears to be very important for the development of ataxia.

Many researchers study different inherited ataxias by expressing mutant proteins in Purkinje cells in mouse models of these diseases. For example, the first mouse model created for spinocerebellar ataxia type 1 (SCA1), called ATXN1[82Q], expresses mutant Ataxin-1 only in Purkinje neurons. These mice develop balance and movement deficits and were critical for increasing our understanding of how Purkinje neurons influence how SCA1 progresses.

If you would like to learn more about Purkinje cells, take a look at this Encyclopaedia Britannica article.

Snapshot written by Dr. Marija Cvetanovic, edited by Dr. David Bushart



Hunting for a needle in a haystack: Scientists identify the gene that causes ARSACS

Written by Dr. Sriram Jayabal Edited by Dr. Brenda Toscano-Marquez

Scientists uncover SACS, a gene containing the largest exon identified in vertebrates, which leads to ARSACS when mutated.

What is your morning routine? Coffee first, right? Now, try to think of all the diverse movements you need to make to accomplish this routine. For instance, just to get a cup of coffee, you have to complete a sequence of motor tasks: you start by pulling the pot out of the machine, then you walk to the tap, fill the pot with water, walk back, pour the water into the machine, put your coffee in, and then finally turn on the machine.

needle in haystack
Picture courtesy of Pixabay

To perform any of these movements, your brain needs to communicate with dozens of muscles in your body. Unfortunately, in people who are affected by hereditary ataxias, the brain loses the ability to coordinate these precise movements. These diseases primarily affect the way patients walk (the symptom that defines “ataxia”), eventually forcing them to use a wheelchair for the rest of their lives.

Hereditary ataxias can be broadly classified as either dominant or recessive. Dominantly-inherited ataxias can be passed down even if only one of the parents is affected; therefore, the disease does not skip generations. Recessive ataxias are inherited from parents who are both carriers of the disease mutation (and who do not usually show any symptoms). Therefore, recessive ataxias can skip generations.

One such recessive ataxia is called Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS). It was first discovered in people from the Charlevoix-Saguenay-Lac-Saint-Jean region of Quebec, Canada [1]. In this region, it is estimated that one out of every 22 individuals is a carrier for the disease mutation [2]. Though prevalent in this specific area of Canada, ARSACS has now been identified all across the world. Symptoms usually start in early childhood when toddlers are learning to walk. These children experience stiffness in the legs (spasticity) and incoordination in their gait (ataxia), leading them to fall more often. They also have difficulties writing, speaking, and performing tasks that require manual dexterity (usually actions that involve hand movements, like reaching for and grasping an object). They continue to experience worsening gait as they age, often needing a cane or handrail to move around by the time they reach adolescence. Around this time, many patients also experience retinal hypermyelination (an eye abnormality) and peripheral neuropathy (damage to the nerves throughout the body). By their thirties, they become dependent on a wheelchair. There is currently no cure for ARSACS, so it is imperative to study this disease’s underlying causes to identify effective treatments.

Continue reading “Hunting for a needle in a haystack: Scientists identify the gene that causes ARSACS”

SCAsource Turns 6 Months Old!

Today marks the six-month anniversary of the SCAsource website launch. A big thank you to all who have read our posts and have come back for more! It is really exciting to see SCAsource grow from an idea shared between colleagues to an actual website that people read.

chocolate cupcake with "Happy Anniversary" topper in front to sign which says "Happy Six Month Anniversary SCAsource!"
Celebratory cupcake purchased to mark the six month anniversary of the SCAsource website. It was very delicious.

Another thank you to all our volunteers who help to write, edit, and proofread content for the site. SCAsource wouldn’t be possible without your help.

We are looking forward to seeing how SCAsource continues to grow over the next few months and years. Today though, we are excited to celebrate what we have done and are happy to announce a brand-new type of article we will be testing out.

Over the past few months, we’ve had some messages from readers asking us specific questions such as: What is DNA? What are clinical trials? What are Purkinje cells? Inspired by these questions, we are excited to announce SCAsource Snapshots.

SCAsource Snapshot logo with a camera "snapping" a picture
The new logo of SCAsource Snapshots

Snapshots are short entries on a single scientific concept or topic. They’ll explain what a topic is and how it ties into ataxia research. We have 12 topics lined up based on your suggestions to try out this new style. Snapshots will be uploaded every other week starting next Friday, April 5. Please let us know what you think!