eQTL for Dummies – Usefulness
Now that we know what an eQTL (expression Quantitative Trait Loci) is in broad terms, we can discuss “why” we would like to make an eQTL analysis.
We all know about the existence of genetic diseases, also we know that those diseases are produced by some differences on the DNA (thats why they are called ‘genetic’). It’s not difficult to imagine that if we need some protein complex to do a specific job but some of the genes (the DNA sequence) that produce some of those proteins have changed, then the whole complex could cease to work or at least work differently. This is what happens in cancer cells, in some types of cancers, for example, the genes that control the process of apoptosis (cell death) get screwed and those cell just don’t ‘hear’ the body orders for them to die, and there you go… cancer!
So, what do we have? First, a complex disease that we don’t fully understand which have so many variables we don’t know where to start looking, and second, the possibility that those variables are not all related to just changes in the coding sequences of the DNA. In that second possibility is that eQTL analysis comes into play, what we are going to look for is that maybe the protein complex is not working as it is suppose to work not because there is something wrong with the parts, but because there is something wrong with the number of parts.
Let’s make an example, imagine a car, if the car stop working it can be for many different kinds of reasons, like a bad engine, no gas or it is stuck on the sand, who knows, so many possibilities! So, imagine a common problematic part of the car, the tires; what is your first guess? flat tires!? Maybe, we can presume that the tires are flat and we just need air to inflate them again, you may see this as our first approach, one of the necessary parts of the car is broken (similar to “there maybe some non-functional protein, lets search for the change in the DNA”) but, could it be that the problem is that there are only 3 tires? That’s an expression problem, the problem is not that the tires are flat, there are 3 beautiful, inflated and perfectly working tires, the problem is that we need four!
Going back to diseases, there are genetic diseases in which the problem is a difference on the amount of proteins working for a process, an those problems are not related to difference in the coding region of any protein but in genetics factors related to gene expression.
Ok, very altruistic, right? we want to help to find a fix to every genetic disease, but, actually, we also want to understand the relation between genes, just for the hell out of it (not really); we want to know how the expression or regulation of some genes make other genes to be expressed or regulated, eQTL analysis also helps us with this. After looking the behavior of gene expression in some diseases we have more information about what genetics factors are associated with what genes, we call that information “markers” and for markers produced by eQTL we call them eSNP, and with this markers and other markers giving information to GWA (Genome Wide Association) studies we can better predict the risk for diseases and better understand how those diseases will try to kill us.