DNA, nucleotide
DNA is a molecule that carries the information required for a single cell to develop into a fully grown organism. DNA is made of simpler units called nucleotides, linked together. Two chains of nucleotides (strands) wind around each other to form a double helix. The variable part of a nucleotide is a chemical group called a base. There are four different bases (A, C, G and T), and the order in which they occur is referred to as the DNA sequence – it is this that carries (encodes) the information. (Chemically, DNA, RNA and antisense oligonucleotides are nucleic acids.)

Gene, codon, amino acid, protein
A gene is a stretch of DNA that encodes a protein or RNA product. For genes encoding proteins, the bases are read in groups of three, and each group is known as a codon. Each codon specifies a building block called an amino acid – and a chain of these forms a protein. The correspondence between codons and amino acids is called the genetic code. The order of amino acids is sufficient to determine the structure and properties of a protein.

Transcription, transcription factor
Transcription is the process by which the information content of DNA is copied into RNA. (Transcription is performed by a protein called RNA polymerase, which is under the control of many different transcription factors. The protein α1ACT functions as a transcription factor.)

Translation, ribosome
Translation is the process by which the information content of mRNA is decoded to make protein. (Translation is performed by ribosomes, enormous complexes containing RNAs and proteins).

Antisense Oligonucleotide (ASO): short single-stranded nucleic acid designed to be used as a drug. Various chemical modifications enhance stability, uptake into cells and target binding, and minimize toxicity.

Gene expression: the process of converting the information content of a gene into protein or RNA products.

Glutamine: one of the 20 naturally occurring amino acids, and is represented by the letter ‘Q’. Two codons (CAG and CAA) specify glutamine. Within the CACNA1A gene, a CAG tract (ie. CAGCAGCAG...) encodes the polyglutamine (polyQ) tract (ie. QQQ...) that occurs in the proteins α1A and α1ACT.

IRES: specialized stretch of mRNA that adopts a complex 3D structure. This structure can be recognized by ribosomes, which are ‘tricked’ into starting translation within – rather than at the beginning of – the message. The existence of an IRES cannot be predicted from the mRNA sequence, and therefore must be proved experimentally.

miRNA (micro RNA): short strand of RNA used by the cell to help control the expression of a gene.

mRNA (messenger RNA): essential intermediate between a gene and the protein that it encodes.

Mutation: change in the sequence of DNA, inherited by the offspring of an organism. In SCA6, the change is an increase in the length of the CAG tract – resulting in an increase in the length (an expansion) of the polyQ tract.

RNA: closely related to DNA, and performs many different functions within the cell. Whereas DNA is double-stranded, RNA is single-stranded (as are antisense oligonucleotides). RNA is copied from DNA by a process called transcription.

voltage-gated calcium channel (VGCC):channel that spans the neuronal cell membrane and allows calcium ions to enter in response to electrical activity; this is important for neuron function. A complete VGCC comprises several protein subunits. The CACNA1A gene encodes the main pore-forming subunit (α1A) of one particular (‘P/Q’) type of VGCC.