In this blog post, we will talk about genetic alterations, their causes and types.
Did you know that all human beings share 99.91% of their genetic information? This means that What makes us unique depends solely on that remaining 0.1% that varies between individuals of our species and that determines our physical characteristics (phenotype), as well as the way in which we respond to environmental factors.
Want to know more? In this article we delve deeper into the different types of genetic alterations that the genome can present, and how science has advanced in its knowledge and in the development of applications since the publication in 2003 of the complete sequence of the human genome.
Key concepts
It is necessary to clarify a series of key concepts to understand the possible genetic alterations that give rise to our “individuality”. As we already explained in Genes and chromosomes: how do they determine our life and our health? and other articles on our blog, DNA stands for DNA Áacid DesoxyriboNucleic, a complex molecule found in the nucleus of the vast majority of cells in our body.
DNA contains the instructions for the creation and functioning of the cells in our body: from hair color to the genetic diseases we can develop.
The DNA sequence is represented in a simplified way according to the nucleotide base:
- Adenine (A)
- Thymine (T)
- Guanine (G)
- Cytosine (C)
Nucleotides are therefore differentiated by the base they contain, and the DNA sequence is represented in a simplified way according to the nucleotide base as A, T, C, or G. The structure of DNA is formed by two complementary strands of nucleotides, which are joined in a specific way: A with T and C with G, and constitute the nucleotide base pairs of DNA. Both strands coil around each other to form a double helix.
Central dogma of molecular biology
DNA contains the instructions, but on its own it cannot carry out all the functions that take place in the body. Proteins are responsible for executing these functions, and the process by which DNA is transformed into a protein is described. the central dogma of molecular biology. In the DNA sequence we find certain regions known as genes, that contain the information to give rise to proteins, which perform specific functions in the body.
Within cells, there is a whole machinery responsible for ensuring that this process is carried out correctly. First, the DNA HE transcribe a RNA messenger (mRNA) in the cell nucleus. In this process, the nucleotide T (thymine) is replaced by U (uracil) in the (single-stranded) mRNA that leaves the nucleus and, thanks to special structures called ribosomes, is translate a protein which is made up of a sequence of amino acids.
But… if RNA is made up of the combination of 4 bases and proteins are made up of the combination of 20 different amino acids, how does translation work?
The answer lies in the genetic code described in the 1960s, for which RW Holley, G Khorana, and MW Nirenberg received the Nobel Prize in Medicine. In the mRNA sequence, nucleotides are read in groups of three, forming a codon that is translated into a specific amino acid, as we can see in the table below. These “signals” or codons encode the amino acids that will form the proteins.
Finally, genome and exome, what is the difference?
The complete set of DNA of an organism is called its genome.. In the case of humans, the genome contains more than 6 billion nucleotides. In fact, if we took the entire DNA sequence of a single cell and stretched it out, it would be more than 2 meters long. But of those 6 billion nucleotides, we currently know that only a small part, approximately the 2%, contains information to form proteins, that small fraction is what represents the exome.
Therefore, we say that The exome is the coding region of DNA, While the rest of the DNA corresponds to non-coding regions, which do not contain information for synthesizing proteins. And if it doesn't code for proteins, what function does non-coding DNA have? Well, for a long time it was considered "junk DNA," however, thanks to scientific advances, we know that non-coding DNA has multiple functions, among which the regulation of the expression of other genes stands out.
Having reached this point…
What are genetic alterations?
Any change in the DNA sequence can alter the genetic code and, therefore, may alter the synthesis of the protein it codes for.
For example, if we look at the genetic code table, the codon CAA it translates into the amino acid glutamine, while AAA translates into lysine, Therefore, changing one nucleotide for another (C for A) changes the protein's composition and may affect its proper functioning. But, if the change is to UAA, This codon, instead of giving rise to glutamine, is a stop codon, so the synthesis of the protein stops.
Therefore, the clinical implications of a genetic alteration will depend on where it occurs, that is, whether it takes place in the coding region (exome) or not, and also whether the alteration causes a drastic change in the synthesis of the protein and therefore in the function that it carries out in the organism.
What types of changes can there be?
The example we saw earlier is a substitution, since it involves the change of one nucleotide for another, but there are more types of genetic alterations, generally speaking:
- Substitution: change from one base to another.
- Deletion: removal of a series of bases.
- Duplication: duplication of a base fragment.
- Investment: inversion of the order of a base sequence.
Why do genetic alterations occur?
We can say that, in general, genetic alterations have two origins:
- Due to external factors, of an environmental nature.
- Due to internal factors, of a genetic nature.
The human body regularly renews almost all of its cells through cell division, resulting in two daughter cells. During this division process, errors can occur, leading to genetic alterations. External factors such as tobacco use and solar radiation, among many others, increase the likelihood of these errors. These genetic alterations, which affect only the cell in which the error occurred, are called somatic, and are not passed on to offspring.
However, genetic alterations can also be present from birth. If the egg or sperm has an error in its genetic material, this will be transmitted to the zygote and will be present in all its cells, since all the cells of the "new" human being originate from that "original" cell. It is also possible for the alteration to occur during embryogenesis (the process of transformation from zygote to embryo), even if the sex cells do not present it. In both cases, these alterations are called germinal, and people who have them can pass them on to their offspring.
Genetic alterations, mutations and polymorphisms
Mutations
You've probably heard of mutations, and you most likely associate the term with something negative. This is for a reason, since mutations are genetic alterations that occur in less than 1% of the population and are associated with a higher risk of developing a disease.
For example, you've probably heard of the gene BRCA1, This gene has the function of controlling cell division to ensure it occurs correctly, preventing tumor formation. When a mutation occurs in this gene, cell division is not controlled, thus increasing the risk of developing a tumor. Specifically, people who have a mutation in BRCA1 They have a lifetime risk of developing breast cancer of between 46%-87%.
Polymorphisms
Polymorphisms are genetic alterations that are present in more than 1% of the population. Most polymorphisms are known as single nucleotide polymorphisms, or SNPs, meaning that the genetic alteration only involves the substitution of one nucleotide for another. Today, millions of SNPs have been described throughout the genome; in fact, it is estimated that there is one SNP for every 100 to 1,000 bases (A, T, G, C) across the genome.
SNPs are responsible for most of what differentiates us from one another; that is, they determine most of the genetic variability between individuals.. Phenotypic traits—observable characteristics such as eye color and height—that distinguish us from one another are determined by genetic polymorphisms. Most SNPs are located in non-coding regions (98% of DNA) and do not have a direct effect on health. Other SNPs located in coding regions (2% of DNA) can influence various aspects of an individual, such as a greater susceptibility to developing a particular multifactorial disease, the development of which is influenced by both genetic and environmental factors.
Genetic variation, key to evolution
Thus, these genetic variations that we all possess in our genetic material are what make us unique. Without genetic variation, there would be no evolution, since the origin of all genetic variation lies in mutations—that is, stable and heritable changes (in successive generations) in the genetic material. Mutations increase genetic diversity, but they do not serve an adaptive purpose, as they occur randomly.
Each species has a different mutation rate, modulated by natural selection so that it can cope in a balanced way with the dual situation of stability-change, inherent in every environment.
Would you like to know what defines you genetically?
At the beginning of the 21st century, the first draft of the human genome sequence was published. Thanks to the participation of international institutions, it was possible to carry out the Human Genome Project which was developed between 1990 and 2003. The project had an initial budget of 3 billion dollars and the ultimate goal was to decipher the complete sequence of the human genome, That is, to obtain the entire linear text consisting of the sequence of As, Ts, Cs and Gs that make up DNA.
These scientific advances ushered in the genomic era in the fields of biology and medicine and made it possible to establish the sequence of the reference human genome, That is, the sequence of a generic genome through which we can now analyze the genome of each person.
Now you know why people have different physical traits, show greater aptitude for a particular sport, or even have a higher risk of developing a certain disease. It all depends on that 0.1% gene that makes us unique. The ability to detect these genetic alterations preventively is fundamental to adapting our lifestyle to our genetics and improving our quality of life.
At Zogen we offer you that possibility, to get to know yourself even better and improve your life and the lives of those around you. The Comprehensive Genetic Testing Package It includes all preventive genetic tests for health, ancestry, personality, nutrition and sports, skin and pharmacogenetics, allowing you to learn about many genetic aspects related to your health, with the most complete package.
What seemed like science fiction just a few decades ago is now a reality within your reach. with which you can access valuable information on preventive and personalized medicine.
