Do you know what genetic alterations are? Did you know that all human beings share 99.9% of their genetic information? This means that Our uniqueness lies in the remaining 0.1 %, which varies between individuals and determines our physical characteristics (phenotype), as well as how we respond to environmental factors.
In this article we delve deeper into the different types of genetic alterations that can occur in the genome. As well as how scientific knowledge and solutions have progressed since the publication of the entire human genome sequence in 2003.
Key concepts
To understand the possible genetic alterations that create our “individuality,” we should clarify some key concepts. DNA stands for deoxyribonucleic acid, a complex molecule found in the nucleus of the vast majority of cells in our body.
DNA carries the instructions for the creation and functioning of our body's cells: from the color of our hair 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)
Therefore, nucleotides are distinguished by their base, 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 has two complementary strands of nucleotides, which are joined in a specific way: A with T and C with G, and both strands wrap around each other to form a double helix.
The central dogma of molecular biology
DNA contains the instructions, but it cannot perform all the functions that take place in the body alone. Proteins are responsible for carrying out these functions, and the process by which we obtain a protein from DNA is captured by the central dogma of molecular biology. In the DNA sequence we can find certain areas known as genes, that contain the information to produce proteins. These proteins perform specific functions in the body.
There is a whole mechanism within cells to ensure that this process is carried out correctly. First, the DNA HE transcribe in messengerRNA (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 into protein which is made up of a sequence of amino acids.
But… if RNA is formed with a combination of 4 bases and proteins are formed with a combination of 20 different amino acids, how does translation work?
The answer lies in the genetic code outlined in the 1960s, for which RW Holley, G Khorana, and MW Nirenberg were awarded the Nobel Prize in Medicine. In the mRNA sequence, nucleotides are read in threes, forming a codon that is translated into a specific amino acid, as shown in the following table. These “signals” or codons encode the amino acids that will form the proteins. Among these, there are 4 special signals:
- AUGUST: marks the beginning of the translation
- UAA, UAG, UGA: these are the stop codons, which indicate that the translation is complete.
Finally, what is the difference between the genome and the exome?
The entire set of DNA in an organism is called the genome.. For 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, only a small fraction are currently known to be identifiable.approximately the 2 %) contains protein formation information, that small fraction being the exome.Therefore, we describe the exome as the coding region of DNA, while the rest of the DNA comprises non-coding regions, which do not contain information for protein synthesis.
So, if it doesn't code for proteins, what is the function of non-coding DNA? For a long time, it was considered "junk DNA," however, scientific advances have revealed that non-coding DNA has multiple functions, the most important of which is regulating the expression of other genes.
So, having reached this point…
What are genetic alterations?
Any change in the DNA sequence can alter the genetic code and, therefore, can alter the synthesis of the protein it encodes.
For example, if we look at the table of genetic codes, the codon of CAA it translates into the amino acid glutamine, while the AAA translates to lysine, Therefore, changing one nucleotide for another (C to A) changes the protein's composition, which could impair its function. But, if the change is to UAA, Instead of producing glutamine, this is a stop codon, so it stops protein synthesis.
Therefore, the clinical relevance of a genetic alteration will depend on where it occurs, i.e., whether it takes place in the coding region (exome) or not, and also on whether the alteration leads to a drastic change in protein synthesis and, therefore, in its function in the body.
What kind of changes might occur?
The example shown above is a substitution, since one nucleotide is exchanged for another, but there are other types of genetic alterations, more generally:
- Substitution: change one base for another.
- Elimination: removal of a series of bases.
- Duplication: duplication of a part of the bases.
- Investment: inversion of the order of a base sequence.
Why do genetic alterations occur?
There is two Main causes of genetic alterations:
- External and environmental factors.
- Internal and genetic factors.
Almost all cells in the human body are regularly replaced. To do this, cells divide into two daughter cells. Errors can occur during this division process, leading to genetic alterations. External factors, such as tobacco or solar radiation, among many others, increase the likelihood of such errors occurring. We call these somatic mutations, because they only affect the cell in which the error occurred, and are not transmitted to offspring.
However, genetic alterations can also be present from birth. If the egg or sperm has a genetic error, this will be transmitted to the zygote and will therefore appear in all its cells, since all the cells of the developing 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 it does not appear in the sex cells. In both cases, these alterations are called mutations. of the germline, and people who have them can pass them on to their children.
Genetic alterations, mutations and polymorphisms
Mutations
You've probably heard of mutations, and you likely have a negative association with the term. There's a reason for this, as mutations are Genetic alterations that occur in less than 1% of the population and are related to a higher risk of developing a disease.
For example, you've probably heard of the gene BRCA1. The function of this gene is to properly control cell division to prevent tumors. A mutation in this gene results in uncontrolled cell division, which increases the risk of developing a tumor. More specifically, people who have the aBRCA1 mutation They have a 46% lifetime risk of developing breast cancer.
Polymorphisms
Polymorphisms are genetic alterations that occur in more than 1% of the population. Most polymorphisms are what are known as single nucleotide polymorphisms, or SNPs, meaning that the genetic alteration only involves the exchange of one nucleotide for another. Today, there are millions of known SNPs distributed throughout the genome. In fact, it is estimated that there is 1 SNP for every 100 to 1,000 bases (A, T, G, C) in the entire genome.
SNPs are responsible for 90% of the things that distinguish us from each other; that is, they determine most of the genetic variability between individuals.. Phenotypic traits—that is, visible 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 directly affect health. Other SNPs located in coding regions (2% of DNA) can influence different aspects of an individual, such as increased susceptibility to a particular multifactorial disease, the development of which is influenced by both genetic and environmental factors.
Genetic variation, the key to evolution
Therefore, these genetic variations that we all have in our genes are what make us unique. If there were no genetic variation, there would be no evolution, since the origin of all genetic variation is mutations—that is, stable and heritable (in successive generations) changes in genes. Mutations increase genetic diversity, but they don't have an adaptive purpose because they occur randomly.
Each species has a different mutation rate, modulated by natural selection so that it can cope with the duality of stability and change inherent in any environment, in a balanced way.
Would you like to know what defines you genetically?
The first draft of the human genome sequence was published at the beginning of the 21st century. Human Genome Project It was carried out between 1990 and 2003, and involved several international institutions. With an initial budget of $3 billion, the ultimate goal of the project was to decipher the entire sequence of the human genome, In other words, to obtain all the linear text comprising the sequence of As, Ts, Cs and Gs that make up DNA.
These scientific advances marked the beginning of the genomic era in biology and medicine and allowed us to establish the sequence of the human reference genome, That is, the sequence of a generic genome through which we can now analyze a person's genome.
Now you know why people have different physical traits, demonstrate greater aptitude for a particular sport, or even have a higher risk of developing a specific disease. It all depends on that 0.1 % that makes us unique. Being able to detect these genetic alterations preventively is essential if we want to adapt our lifestyle to our genetic makeup and, therefore, improve our quality of life.
That's possible with Zogen. Learn more about yourself and improve your life and the lives of those around you. Zogen test My Genome It sequences your entire genome and teaches you about various genetic aspects of your health.
Something that seemed like science fiction just a few decades ago is now a reality within your reach., providing you with access to valuable information and personalized preventive medicine.
This article is based on the original article written by Maria Moreno, Medical Sciences Liaison Manager at Veritas Intercontinental.
