Scientific background

What is DNA?
DNA consists of biochemical building blocks called nucleotides of 4 different types: adenine, thymine, cytosine and guanine (abbreviated as A,T,C and G), which are lined up in a specific sequence forming long polymeric molecules called chromosomes. Every nucleus of a human cell contains 46 chromosomes, 23 which you inherited from your mother and another 23 from your father. Structurally the DNA sequence presents itself in the form of a double helix which is why the nucleotides are also referred to as base pairs. In the human genome, these polynucleotide chains range in size from approximately 50 million base pairs (for the smallest chromosome) to 250 million base pairs (for the largest chromosome) adding up to a total of around 3,2 billion nucleotide pairs.
What is a gene and what is the exome?
Within the primary structure of DNA, sections of the sequence called “genes” carry the information for the synthesis of all functional proteins in our body. Humans have about 21.000 genes, which are distributed amongst the chromosomes. The genes themselves are composed of sections that contain the information for amino-acid sequences (exons), interspersed with non-coding sections (introns). In total, the sum of all amino-acid coding sequences (exome) that controls protein synthesis takes up only about 1,5 % of the total DNA sequence in the human genome. By sequencing the exons and discarding the non-functionally related DNA fragments, Whole Exome Sequencing is a cost and time effective alternative to sequencing the whole genome. It provides a balanced coverage of 20.965 genes and maximizes variant information output.
What makes everybody unique?
Although 99,9 % of the genetic sequence is conserved amongst all humans, small variations referred to as SNP (single nucleotide polymorphisms) or INDELs (insertions and deletions) and other structural differences make every individual DNA sequence unique. Variations occurring within the coding regions of a gene can produce variations in the resulting protein or even abolish its synthesis.
Certain DNA patterns called “variants” have been associated with clinical aspects. Since the first human reference genome was published in 2001, the scientific community has been contributing their findings in genomic databases with an exponentially growing amount of information. By comparing your personal sequence with the available data, it is now possible to retrieve accurate information about the functioning of your body, identify problem-related genes and evaluate how your variants are affecting or will affect you in the future.
How is the synthesis of proteins from DNA regulated?
A complex network of cell signalling molecules communicate with the nucleus of each cell to inform about the conditions outside the nucleus. As an example, normally every person obtains cholesterol through food, which is generally considered as a negative thing because many people in developed countries have too much of it. Nevertheless, cholesterol is an important molecule in the composition of cell membranes. If at a certain point the cell detects a shortage of cholesterol, a signalling molecule will pass information to the nucleus of the cell, where transcription factors will activate the transcription of the necessary genes so the body can make cholesterol itself. This transcription consists in copying the DNA sequence of the gene into a molecule of RNA. The RNA molecule will then leave the cell nucleus and migrate to the cytoplasm of the cell, where it is translated into the proteins that can make cholesterol.
Apart from the sequence of the genes itself, a process called “DNA methylation” is very important for maintaining general health. It is a mechanism that regulates the transcription of the genes so that the amount of RNA that is copied from the genes is just right and the correct amount of proteins is synthesized.
DNA methylation keeps the functioning of our whole body under control. If it gets imbalanced, it increases the chances for many diseases such as cancer, heart problems, neurological diseases, etc. Vitamins B9 (folate) and B12 (cobalamin) are important methyl donors and cofactors for this process.