Genetic Profiling: What is it & What Information Does it Give Us?
Preventive personalised digital health “doctor" iamYiam has joined EuropeActive/EREPS as a new member. This company combines big health data, academic research, algorithms and your own proteins to be able to tell you exactly "who you are". How does it work? What information do you receive and is it helpful? Let's dive into the matter.
Proteins are the second largest constituent of the human body after water and play such vital roles that, in effect, they define who we are. They are large, complex molecules made of hundreds or even thousands of amino acids. The average protein contains around 500 amino acids and the longest known protein includes nearly 30,000 amino acids. The proteins that our body uses are manufactured within our cells from the basic amino acid constituents.
Let’s digress for a second and talk about amino acids. There are twenty amino acids, nine of which the human body cannot manufacture and need to be provided by what we eat. The body doesn’t actually use the proteins that we ingest as such, it breaks them apart to keep a reserve of the constituent amino acids that will then be used to build new proteins. The exact number of different proteins is not known, but it is clearly larger than 10,000. Certain essential proteins will be manufactured in every cell, irrespective of their type, others will only be manufactured in certain cell types such as skin cells, eye cells, brain cells etc. Cells find the very complex ‘recipes’ for all these proteins in our DNA. This is the purpose of our DNA. It carries the code used by our cells to construct the many different proteins that are essential to our functioning. However strange it may appear, it is really just a code - and quite a simple one at that, but very long!
What is DNA?
The complete set of DNA coding information for a particular living organism is called the genome. The human genome is a three billion long series of four different nucleotides. Nucleotides are biological molecules usually called by their initial i.e. T-Thymine, C-Cytosine, A-Adenine, or G-Guanine. Cells read these letters three at a time, so in effect a DNA strand is like a long sentence made of maybe one billion three-letter words. The complete set of DNA information for a particular living organism is called its genome.
In reality, it is not one strand, but two nearly identical strands that are joined together at each nucleotide (letter).The rule is always the same: A is attached to a T, while C is attached to a G -and vice-versa. So, in effect, both strands are complementary. If the leading strand reads ATAAGGC, the lagging strand will invariably read TATTCCG. So both strands are not identical, but they only carry one code. The full length of one DNA strand is approximately 1.8 metres but its very specific molecular setup makes it twist and roll up on itself very tightly so its actual size in the body is microscopic. That is good news, since every cell contains our entire DNA information and we have approximately thirty-seven thousand billion cells! Within each cell, the full genome is cut into 23 different parts called chromosomes, each containing a portion of our full DNA.
Genes, SNP and genotype
Luckily, it seems that only a fraction of that code serves any purpose. The actual protein recipe is only contained within specific portions of the DNA strand called genes. Together the genes represent only about a quarter of our entire genome, and even within the genes, only a fraction of the code is really used for coding (the exons). So, in total, only approximately 1.5% of the whole DNA chain contains real coding information. Another 7% of the genome, although non-coding, plays a very important role in determining which genes are expressed within cells and under what conditions. The remainder, a staggering 92%, is pretty much useless and sometimes called ‘junk DNA’.
Human DNA contains approximately 20,000 genes, each gene being a different recipe for one specific protein. 99.9% of the code is identical across all humans. In fact, a lot of the DNA is shared by most living species - we share 95% of our DNA with chimpanzees and nearly 50% with bananas! We won’t look at a naked man in quite the same way anymore… So there exist very few differences quantitatively (i.e. c. 0.1% of the whole genome) but they are responsible for massive visible differences that account for our individual uniqueness. The most consequential differences in the code are a simple one letter difference in a chain. A single nucleotide difference can chose between blond or dark hair, blue or brown eyes and between predisposition levels to serious health conditions.
These one-letter differences are called single nucleotide polymorphisms or SNP (pronounces ‘snip’). These SNPs are what makes us unique and they are what genetic profiling will be analysing to define our unique code. Since we are on vocabulary, our unique combination of letters (the whole 99.9% that we share with everyone and the 0.1% that is unique) is called our personal genotype.
How does it all work in practice?
We all had some form of introduction to the laws of genetics in our biology classes at school and often we worked on the colour of our eyes as the illustration. But how does the algorithmic sequence of inherited recessive and dominant genes that determined the colour of our eyes relate to genotypes, SNPs and 4-letter codes? Eye colour is the consequence of the amount of the pigment melanin found in the stroma of the iris in the eye. Lots of melanin gives brown eyes. Less melanin gives green eyes. Little or no melanin gives us blue eyes. The gene linked to the production of melanin is called OCA2. There exist various variants of that gene (SNP) and the differences in DNA coding sequence will spark the production of slightly different proteins by the cells present in the iris. Those proteins will in turn trigger the production of various quantities of melanin that will lead to different eye colours.
How do you know which gene, or which variant of a gene is linked to a particular trait?
Unfortunately, we do not really know how to ‘read’ the code. What we know is the type of protein that will be manufactured from the code. Each three letter combination triggers the inclusion of one particular amino acid into the protein chain, and we know all the possible combinations, of which there are 64 in total (i.e. 4 possibilities for each ofthe 3 letters viz. 4 x 4 x 4 =64). But we do not know in what different ways two nearly identical proteins will behave. Remember that the one SNP difference in a gene will trigger the production of two different proteins that will only differ by one amino acid in the sequence - a sequence that could be hundreds or thousands amino acids long.
So, the way we can know is by doing very empirical research. This research usually goes in one of two directions:
Researchers will compare the genomic sequence of a large group of persons, some of which share a particular physiological trait (such as a particular disease, sensitivity to medicine, physical feature) and will try to find sequences in the genome that are common to those sharing that particular ‘phenotype’ and not to those who don’t. If the frequency of that genetic variant is ‘statistically significant’ (i.e. it is more frequent than statisticians would expect if the distribution was purely random), they can assume an association between that particular variant and that particular physiological trait.
Researchers will also work the other way around. They will look at a group of people whose genotype had been identified and who share a common genetic variant (i.e. a common SNP) and then try to determine if they share similar traits.
These attempts to determine associations between SNPs and specific traits are called Genome-Wide Association Studies(GWAS). To date, researchers have identified only a few thousand such associations and there are approximately two million SNPs in the genome. Assuming that they are distributed along the genome randomly, only 8% of them will fall within ‘useful’ parts. It still leaves nearly 200,000 SNP that need analysing, so we are not quite there yet! The functioning of the human body is immensely complex. Most phenotypes are not just the result of one gene, but of a combination of many biological processes, with a strong influence from the environment. What GWAS offers are probabilities that certain genotypes are linked to particular traits. Rarely are the associations certain and definitive. So at this point in our knowledge, the genetic science is still probabilistic.
What happens after I give a saliva sample?
Lets first answer the question why we use saliva and what do we find in saliva that is relevant to genetic profiling? Traditionally, DNA had been extracted from white blood cells extracted from whole blood. However, studies have shown that a great proportion of the DNA present in saliva also comes from white blood cells. In addition, saliva is one of the most accessible of our body's bio-fluids and allows easy and non-invasive sample collection. Research has since confirmed the reliability of saliva as a source of DNA and it has become the preferred method of collection.
Your DNA would be isolated from the saliva sample and then copied several times using a process called PCR (polymerase chain reaction). Once a large quantity of your DNA has been made, it is cut up into millions of short pieces. These are then made to bind with probing DNA fragments. After that it's possible to identify areas of the DNA where the sequence differs from the probing samples and a computer translates this information into your individual genome profile. This work is performed by our partner XCode Lifesciences in their laboratory.
The genome is then analysed to identify which variant of the code it carries at SNP points that have been associated with a number of nutritional, fitness and health traits. In this way we can present you a map of the unique combination of genetic related predispositions to the following traits:
|Regulation of Eating||Vitamin A Requirement||Aerobic Capacity||Obesity|
|Propensity for Weight Gain||Vitamin C Requirement||Anaerobic Capacity||Type 2 Diabetes|
|Saturated Fat Sensitivity||Vitamin D Requirement||Endurance||Hypertension|
|Polyunsaturated Fat Sensitivity||Vitamin E Requirement||Power||Heart Disease|
|Monounsaturated Fat Sensitivity||Vitamin B6 Requirement||Flexibility|
|Fatty Food Perception||Vitamin B9 Requirement||Muscle Fatigue and Lactate Threshold|
|Bitter Taste Perception||Vitamin B12 Requirement||Muscle injury|
|Sweet Taste Perception||Magnesium Requirement||Injury repair|
|Carbohydrates Response||Calcium Requirement||Exercise and Fat Loss|
|Protein Response||Phosphate Requirement|
|Fibre Response||Iron Requirement|
|Gluten Intolerance risk||Antioxidant Needs|
|Lactose Intolerance risk|
Interested in your genetic make-up and predisposition to the traits above? iamYiam is an affiliate member of EREPS, with a special discount for EREPS members! Please see our affiliate programme here (you have to be logged in) or visit the general iamYiam website for more information on genetic profiling and the services this company offers.