Today I wanted to share with you a little about GWAS, a particular type of study that is spearheading our knowledge of genetic diseases and our DNA, from the fascinating world of genetics research.
In 2003 the human genome project was completed – this was an international research collaboration that had one single aim – to determine the sequence of the entire human genome, and identify all the genes it contained. From the project a catalogue of all the most common genetic variations found in humans was catalogued, these variations, called single nucleotide polymorphisms or SNPs for short occur in human DNA, and are distributed among the world population. These SNPs gave birth to GWAS about 10 years ago, or Genome-Wide Association Studies (Bare with me, I know this is heavy on the science front but totally fascinating, and are one of the main tools I use to optimise the Nature x Nurture Equation).
What is an SNP?
Basically, think of the genetic code as a language built of 4 letters – A, G, C and T. The letters stand for one of four nucleotides – Adenine, Guanine, Cytosine and Thymine, these four little things are the very language of DNA, in various triplet combinations called codons, they code for all possible proteins using the three-letter code for all 20 amino acids that are the building blocks of proteins. Scary how four little things are the very basis of DNA, of us, of every living organism (well and the unliving viruses, yes, viruses are not technically alive).
Anyway, so SNPs are variations in a single nucleotide found between members of a biological species or paired chromosomes (chromosomes are a “package” of a single molecule of DNA and scaffolding proteins. We get a set of chromosomes from each parent, giving us 23 pairs), so you can see that variations will exist.
So what is GWAS?
GWAS is an interesting approach to genetic research. Instead of focusing on a few candidate genes, we are interested in (which was the traditional way), researchers examination common genetic variations in different individuals so that we can see if any specific variant is associated with a particular trait (Liou 2013, Leiserson et al. 2013, Korte and Farlow 2013).
Usually, the trait focused on is a disease one, for example, what variants contribute to human diseases. We can gain valuable insights, much more easily (and cheaply), for many common diseases, including new drug targets and discovering potential drug reactions, which obviously is a big deal for our health, and survival as a species (Liou 2013).
The challenge faced here is two-fold:
1. to identify the genes responsible within an identified variation, and this is done by a nifty ranking system where genes are ranked by importance, based on the interaction of these genes with other genes known to be associated with the trait being studied (Leiserson et al. 2013, Korte and Farlow 2013).
2. The missing heritability problem, which is Scienceish for “Detected variants do not explain most of the genetic effects found in affected individuals” (Leiserson et al. 2013). In human speak, it means different collections of variants are present in different patients – This is called genetic heterogeneity, which is just greek for we are all unique.
From the Greek Greek heterogenḗs, hetero meaning different and génos which means kind, or type, the -ity suffix makes the word a noun
Genetic Heritability shows itself on two levels. The first level is where affected individuals may have distinct variations within a specific gene. The second level is that variations may be distributed across different genes within a particular pathway (pathway here denotes a set of related reactions in a metabolic pathway, or a series of signals that lead to a particular gene being expressed or silenced, called a signalling pathway, or one that regulates a particular aspect of our cellular or bodily processes, or regulatory pathway).
One way to solve this problem is the testing of the associations between the trait of interest and different combinations of genes containing potential variations that are responsible for it.
In summary GWAS studies are a type of genetics research that tries to discover if certain variations in DNA (SNPs), play a role within a particular trait (usually a disease). The method involves comparing the DNA of two groups of people, one with a particular trait, or disease and another group without it, and seeing which genetic variations (SNPs) differ between the two groups. The problems faced by these studies is that more than one set of variants may exist for the condition, shared by the population with the trait, the other problem is that the detected variants may not explain the genetic behaviour of a trait fully, because other genes (or variants), or environmental factors and signalling pathway factors may be involved.