Deoxyribonucleic acid (DNA) is a carrier of hereditary (genetic) information, which is carried on from biological parents to their offspring. It is stored in the cell nucleus and build from sugar (deoxyribose), nitrogenous bases (adenine, guanine, thymine and cytosine), and a phosphate group. Genes are the most important parts of the genome which carry the baseline traits of an individual.
A gene is a part of the DNA that carries a transcript for the RNA molecule which can either be translated further into protein (protein-coding genes) or carry out its function as an RNA molecule (non-coding genes). These proteins have vital functions in the cells. Therefore, a mutation of protein-coding genes can change the order of amino acids (building blocks of proteins). This can sometimes manifest as a changed trait (change of eye colour), but more often leads to disease.
Human DNA carries 22.000 protein-coding genes and 18.000 genes that only code for RNA.
Genome is a collection of all genetic material (DNA), both coding and non-coding. Coding DNA represents only 1-2% of all DNA. The rest of the DNA does not encode proteins nor RNA molecules and is poorly researched compared to the coding regions. However, non-coding DNA has an important structural role and protects the coding part of the DNA against mutations.
A chromosome is a single DNA molecule carrying a part of the whole genetic material of an organism. Humans have 23 pairs of chromosomes inherited from their biological parents. During the cell, cycle chromosomes are loosely or tightly coiled around special proteins called histones. During the metaphase of cell division, the chromosomes take up their distinct X-shaped structure. When in this confirmation, it is the easiest to differentiate 23 pairs of chromosomes.
Exome represents the part of the DNA that gets transcribed and translated into proteins. This part of the DNA also carries the majority of known pathological variants that cause hereditary diseases. This is due to the direct influence of the mutation on protein structure.
Rare diseases are defined in the EU as life-threatening or chronic diseases that affect less than 5 in 5,000 people. Currently, there are between 6000 and 8000 rare diseases that affect between 6 and 8% of the European population, or between 27 and 36 million Europeans. Patients with rare diseases require complex medical care, to reduce mortality and increase the quality of life. The treatment of these patients is especially difficult, due to the small number of patients with individual diseases and the dispersion of knowledge and specialised medical centres.
Next-generation sequencing (NGS) is DNA sequencing technology that revolutionised genomic research. While the primary method for DNA sequencing (Sanger method) is highly time-consuming, NGS enables sequencing of the whole genome in just a few hours. There are different NGS platforms available, but they all work on the principle of parallel sequencing of millions of small DNA fragments. These sequences are then puzzled together into a whole genome using bioinformatics. Each of the three billion bases is read multiple times to achieve high precision of data. NGS technology can be used to sequence-specific parts of the genome (exome, specific genes related to a disease) or the whole genome.
The sequencing of the human genome is successfully implemented in the diagnostics of genetic diseases. With the advances in technology, the proportion of the genome that can be sequenced is increasing. Using clinical exome sequencing, more than 4000 genes, associated with genetic diseases can be sequenced, achieving diagnostic success in 22%. When applying the method to the whole exome (coding regions in all human genes), diagnostic success can be achieved in 25-40%.
Whole-genome sequencing is the sequencing of the entire DNA, including coding and non-coding DNA. Compared with exome sequencing, this method is more expensive and time-consuming but offers more precise results. Whole-genome sequencing increases the diagnostic success to above 40%, an important added value of this method for the diagnostics of genetic diseases.
Personalised or precision medicine is healthcare, individually tailored based on the genome, lifestyle and environment of the patient. The advances in genomics and easier access to health data have enabled the integration of personalised medicine into clinical practice.
Each individual carries millions of genetic changes in their genome sequence that have a yet unknown impact on their health. To differentiate between pathogenic variants and benign variants, we need a database of the variants occurring in the general population and their prevalence. Big international databases are missing data on genetic variability in the different populations, especially, poorly represented smaller populations, including the Slovenian population.
National genomic projects represent the basis of all genomic research in the countries, increase the efficiency of differentiation between pathogenic and benign population genomic variability, and thus greatly facilitate the diagnostics of genetic diseases in the countries.