It started here. Without looking anything up, I am going to attempt to define or explain a list of terms from this passage, based on my current understanding.

Do not trust me.

As I grow in my understanding, I’ll be adding improved definitions of the terms to my glossary, and these definitions will appear automatically on mouseover. To achieve this, I use a WordPress plugin called CM Tooltip Glossary.

Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder that is caused by a CAG trinucleotide repeat expansion in the CACNA1A gene. As one of the few bicistronic genes discovered in the human genome, CACNA1A encodes not only the α1A subunit of the P/Q type voltage-gated Ca2+ channel CaV2.1 but also the α1ACT protein, a 75 kDa transcription factor sharing the sequence of the cytoplasmic C-terminal tail of the α1A subunit. Isoforms of both proteins contain the polyglutamine (polyQ) domain that is expanded in SCA6 patients. Although certain SCA6 phenotypes appear to be specific for Purkinje neurons, other pathogenic effects of the SCA6 polyQ mutation can affect a broad spectrum of central nervous system (CNS) neuronal subtypes.

Spinocerebellar ataxia is a movement disorder which results from having wonky dendrites in the spinocerebellar region, i.e. the base of the cerebellum (the ‘movement part’ of the brain) where it goes into the spinal chord.

Autosomal-dominant: Ooh. Um. OK. Somatic means pertaining to movement, so autosomal means… er… self-moving (from auto, meaning self), and dominant means it overrides something… so autosomal dominant means that an automatic movement overrides the movement which you want to make.

Neurodegenerative: Neuro- means pertaining to the nervous system, and degenerative means going kaput slowly, so neurodegenerative means relating to something in the nervous system which is going kaput slowly.

CAG trinucleotide: Oh my goodness. C means cytosine, A stands for adenosine and G is… er… guanine? Tri means three, and a nucleotide is a little snippet of a gene, and er… so a trinucleotide is a triple snippet. This is a conjoined triplet snippet of cytosine, adenosine and guanine, which are all amino acids.

Repeat expansion: Presumably this is a bad thing; the bitty replicates itself. The abovementioned trinuclotide has made two copies of itself, now there are three identical bitties all in a conjoined bunch, where there was supposed to be only one.

CACNA1A gene: An allele (variant) of a CACNA1 gene.

Bicistronic genes:  Oh for goodness’ sake. Bi- means two, and –cis- means on the same side, and -tronic means… er… driven, or something. So, bicistronic genes are genes which drive two processes. Can’t imagine what the -cis- is doing in there.

Human genome: All the genes that go into making a person.

α1A subunit: A specific part of an ion channel.

P/Q type voltage-gated Ca2+ channel CaV2.1:  Let’s start with what a channel is. Ion channels are little fluid-filled doors that let electrolytes in and out of cells. A Ca2+ channel is specially for calcium (Ca2+) which is a cation. CaV2.1 is the name of the type of calcium channel. The Ca bit stands for calcium, the V stands for voltage-gated, and the 2.1 tells you what would open the gate, namely if the ratio of positive to negative charges is 2:1, then it will open, otherwise it will remain closed. P/Q type… oh drat. P/Q type means ‘potential/quotient’ which is some kind of maths thing… can I come back to this one?

α1ACT protein: What? This is a kind of protein, right? Proteins have names. This is the name of a protein.

75 kDa transcription factor: A transcription factor is an ingredient in a recipe for an enzyme (specialised protein) that carries instructions from the nucleus to the mitochondria, where it… Can I come back to this one too? I am thinking in circles now.

Cytoplasmic C-terminal tail of the α1A subunit: This is not a reference from Bladerunner to a specific starship on fire on the shoulder of Orion. Cytoplasm is the main body of a cell, the mushy stuff in which all the organelles are suspended. The C-terminal tail is the calcium atom end of a specific part of the ion channel that touches the cytoplasm. In other words, it sits on the inside rather than the outside of the cell membrane.

Isoforms of both proteins: Isoforms are ‘the same thing in different forms’. In a protein it means that the atoms are identical, they just sit in slightly different places.

Polyglutamine (polyQ) domain: Right! Er… Poly- means many. Glutamine sounds like an amino acid. In fact, it sounds like an amino acid in my molecular chemistry texbook. This makes me think that I may be wrong about what CAG above means. The G could be glutatmine. Your gluteus maximus is your bum. So glutamine is the buttocks of a protein. Except it’s poly, so it has lots of little bum-cheeks, not just two.

Phenotypes: Yay, something I actually sort of know! A phenotype is an externally observed type, as opposed to a genotype, which is a genetic type. In the passage above, certain SCA6 phenotypes means some manifestations of spinocerebellar ataxia.

Purkinje neurons are fancy neurons which become clever if you exercise them, particularly by repetitive movement. A neuron is a nerve cell. It has a starry head which I think is called an astrocyte, and a long stalk, called an axon, and then there are fingers at the end called dendrites. The space between the dendrites of one neuron and the dendrites of the next is called a synapse. Electrons hop over that space. When your Purkinje neurons are exercised, they make all your other neurons interested in learning too, not just in your cerebellum, but also in your cerebrum. You get Purkinje neurons in both of those sections of the brain, maybe in other parts too. They are named after a guy from Eastern Europe. I think he was Hungarian.

Pathogenic effects: Effects that make you sick.

Mutation: Basically, this means a ‘changed gene’. There seems to be quite a lot of politics wrapped up in this term, because people who don’t have standard-issue genes sometimes don’t function well under conditions which are fine for everyone else, and this annoys people. And of course, some mutations result in humans which are simply not biologically viable. Once a specific mutation has been passed on for a generation or two, people call it an allele, or gene variant. (I am tempted to write an essay now, but I will stop here.)

Central nervous system (CNS): The message centre of your body that tells all the parts what to do to keep you alive (as opposed to the peripheral nervous system, which controls sensing and moving). The CNS consists of lots and lots of neurons. It includes your brain, your spine and some other things, and it interacts with your heart and tummy, skin and lungs. It consists of the sympathetic and parasmpathetic nervous system.

Neuronal subtypes are different kinds of different kinds of neurons.

Whew! Right, now I am going to start studying what these things actually mean! Once I am confident of a definition, I will enter it into my glossary. Then when you move your mouse over one of these terms, a better definition will appear.