Setting the scene: Genetics & cell biology – fundamentals

Genetics fundamentals:

- Everyone has own unique DNA (unless you are a monozygotic twin – then chances are, someone else has same DNA as you 😊)

- (In general) Our (human) DNA consists of 23 pairs of chromosomes. In each pair one comes from our mother and the other from our father.

- DNA consists of genes. Genes consist of exons – coding regions, and introns – non-coding regions. Exons are very important  - they are translated into proteins. And you can simply assume that protein conditions how your organism works (or not). Eg. proteins are responsible for the color of your hair, they are fuel for your muscles or orchestrate metabolism. In the past, people thought that 1 protein = 1 function, but today we know it is not true. And PACS2 is a perfect example, participating in many processes. Those exons – part of DNA coding proteins – constitute only 1-3% of our DNA. The rest? It is still not fully clear – some part we understand, but for majority we have only hypothesis.

- DNA is often named “genetic code”, because it is actually the code consisting of 4 different letters, representing 4 different nucleotides (basic building blocks of DNA): adenine (A), cytosine (C), guanine (G) and thymine (T).

- DNA “lives” in the cell nucleus, so the heart of the cell. And never leaves its home 😊And proteins are produced in other places of the cell (we call them “protein-making machinery”).

- How this machinery knows what is the recipe for the protein? RNA. Precisely mRNA (messenger RNA) is a message sent from nucleus to protein-making machinery. 

- Each set of 3 letters (nucleotides) code one of 20 amino acids. So as an example, the set of 30 letters will code protein built of 10 amino acids. In reality, proteins are much more complex -  PACS2 gene has more than 97 thousand letters (to be precise: base pairs; not all are in coding regions, as it was said).

- Important here is also gene expression – meaning in which cells a given protein should be produced, how often and how much of it. Eg. we don’t need a protein responsible for our hair color in our leg! On the other hand, when we map in which cells PACS2 protein is expressed, we can spot what parts of our body can be impacted.

-  Mutations can be:

o   benign,

o   likely benign,

o   uncertain significance,

o   likely pathogenic,

o   pathogenic.

- Mutations are changes in genetic code (let’s say vs average in the society). There are different types of genetic mutations:

o   Deletions - part of our DNA is removed – it may be a small part (from 1 base pair – 1 letter, to huge parts of chromosome including couple of genes)

o   Insertions – some additional nucleotides are inserted into “standard” gene; it may be one letter, it may be more; it may be in one place, there may be more insertions; it may be duplication (part of standard code is unnecessarily repeated) etc.

o   Re-arangements – there may be switch in order of the code

o   Missense mutation – a change of one nucleotide (one letter) to another

-            Those different mutations (if pathogenic) can lead to:

o   Loss of function – leading to underactivity of the protein or complete absence of it

o   Gain of function – leading to overactivity of the protein

o   Toxification – so a changed protein is toxic for our organism

And it may happen it is a mix of effects.

More about fundamentals: https://bertrand.might.net/articles/algorithm-for-precision-medicine/

I also love the way definitions are provided by: https://www.genome.gov/ 

Cell biology:

- Entire human organism consists of cells 😊

- Each cell consists of different organelles (you may remember from biology lessons); you don’t need to learn all of those strange names by heart BUT what would be worth remembering is that there is one very important structure: mitochondria. Why? They are main sources of energy for brain cells. If we have problem there, it usually leads to neurodevelopmental or neurodegenerative issues. And epilepsy. And PACS2 protein is close “friend” with mitochondria, what will be covered in future posts.