Genes Matter

Genetic alterations: the different causes and types

Did you know that all human beings share 99.9% of their genetic information? This means 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.

Want to find out more? In this article we delve into the different types of genetic alterations which can occur in the genome, as well as how scientific knowledge and solutions have progressed since the publication of the entire sequence of the human genome in 2003.

Key Concepts

In order to understand the possible genetic alterations that create our “individuality”, we should clarify a few key concepts. As we explained in “Genes and chromosomes: how do they determine our life and our health?” and other articles on our blog, DNA stands for Deoxyribonucleic Acid, a complex molecule found in the nucleus of the vast majority of our body’s cells.

DNA carries the instructions for the creation and operation of our body’s cells: from the colour of our hair to the genetic diseases we may develop. 

The DNA sequence is represented in a simplified way according to the nucleotide base:

  • Adenine (A)
  • Thymine (T)
  • Guanine (G) 
  • Cytosine (C)

The nucleotides are thus 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. DNA’s structure has two complementary nucleotide strands, which bind in a specific way: A with T and C with G, and form the nucleotide base pairs of DNA. Both chains are wrapped around each other to form a double helix. 

Central dogma of molecular biology 

DNA contains the instructions, but it cannot carry out all the functions that take place in the body alone. Proteins are in charge of performing these functions, and the process by which we get from DNA to a protein is captured by the central dogma of molecular biology.  In the DNA sequence we can find certain areas known as genes, which contain the information for producing proteins. These proteins carry out specific functions in the body.

There is an entire mechanism within the cells to ensure that this process is carried out correctly. First, the DNA is transcribed into messenger RNA (mRNA) in the cell nucleus. In this process the T (thymine) nucleotide is replaced by U (Uracil) in the mRNA (single-stranded) leaving the nucleus and, thanks to special structures called ribosomes, it is translated into protein which is formed by 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 for medicine. In the mRNA sequence the nucleotides are read in threes, forming a codon that is translated into a specific amino acid, as shown in the table below. These “signals” or codons encode the amino acids that will form the proteins. Among these, there are 4 special signals:

  • AUG: 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 genome and exome? 

The whole 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 whole DNA sequence of a single cell and stretched it out, it would be over 2 metres long. But of those 6 billion nucleotides, only a small part (approximately 2%) are currently known to contain protein-forming information, that small fraction being the exome.  Therefore, we describe the exome as the coding region of the DNA, while the rest of the DNA comprises non-coding regions, which do not contain information for protein synthesis. So if it does not code for proteins, what is the function of non-coding DNA? For a long time, it was considered to be “junk DNA”, however, scientific advances have revealed that non-coding DNA has multiple functions, the most important of which is to regulate 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 may alter the synthesis of the protein that it encodes. 

For example, if we look at the genetic code table, the CAA codon is translated into the amino acid glutamine, while AAA is translated into lysine, so the change of one nucleotide for another (C for A) changes the composition of the protein, which could impair its function. But, if the change is to UAA, instead of giving rise to 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 whether the alteration results in a drastic change in protein synthesis and therefore its function in the body.

What sort of changes might occur?

The example shown above is a substitution, as one nucleotide is exchanged for another, but there are other types of genetic alterations, more generally: 

  • Substitution: exchanges one base for another. 
  • Deletion: elimination of a series of bases.  
  • Duplication: duplication of a portion of bases. 
  • Inversion: inversion of the order of a sequence of bases. 

Why do genetic alterations occur?

There are two main causes for genetic alterations:

  • External, environmental factors.
  • Internal, genetic factors.

Almost all of the cells in the human body are regularly replaced. To do this, the cells divide into two daughter cells. Errors can occur during this division process, leading to genetic alterations. External factors such as tobacco or the sun’s radiation, among many others, increase the likelihood of such errors taking place. We call these somatic mutations, because they only affect the cell in which the error has occurred, and they are not passed on to offspring.

However, genetic alterations can also be present from birth. If the egg or the sperm cell 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 “new” human being originate from that “original” cell. It is also possible for the alteration to happen during embryogenesis (the transformation process from zygote to embryo), even if it does not appear in the sex cells. In both cases these alterations are called germline mutations, and individuals that have them can pass them on to their offspring.

Genetic alterations, mutations and polymorphisms


I’m sure you’ve heard of mutations, and you probably have a negative association with the term. There is a reason for this, since mutations are genetic alterations that occur in less than 1% of the population and are linked to a higher risk of developing a disease.  

For example, you’ve probably heard of the BRCA1 gene. This gene’s function is to properly control cell division in order to prevent tumours. A mutation in this gene results in uncontrolled cell division, which increases the risk of developing a tumour. More precisely, people who have a BRCA1 mutation have a 46%-87% risk of developing breast cancer in their lifetime.


Polymorphisms are genetic alterations that occur in more than 1% of the population.  Most polymorphisms are what is known as single nucleotide polymorphism or SNP, meaning that the genetic alteration only affects the exchange of one nucleotide for another. Today there are millions of known SNPs distributed across the genome. In fact, it is estimated that there is 1 SNP for every 100 to 1,000 bases (A, T, G, C) throughout the genome. 

SNPs are responsible for 90% of the things that distinguish us from one another, i.e. they determine most genetic variability between individuals. Phenotypic traits, i.e. visible features such as eye colour and height, which differentiate us from each other, are determined by genetic polymorphisms. Most SNPs are found 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 a greater susceptibility to a particular multifactorial disease, whose development is influenced by both genetic and environmental factors.

Genetic variation, the key to evolution 

Thus, 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 either, since the origin of all genetic variation are mutations, i.e. stable and hereditary changes (in successive generations) in the genes. Mutations increase genetic diversity, but do not have an adaptive purpose, because they occur by chance.

Each species has a different mutation rate, modulated by natural selection so that it can cope with the duality of stability and change inherent to 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. The Human Genome Project was carried out between 1990 and 2003, and it involved various international institutions. With an initial budget of 3 billion dollars, the project’s end goal was to decipher the whole 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 ushered in the genomic era in biology and medicine and enabled us to establish the sequence of the human reference genome, i.e. the sequence of a generic genome through which we can now analyse a person’s genome.

Now you know why people have different physical traits, demonstrate more capacity for a certain sport, or even have a higher risk of suffering from a particular disease. It all depends on that 0.1% that makes us unique. Being able to detect these genetic alterations in a preventative way is essential if we want to adapt our way of life based on our genetics and thus improve our quality of life.

That is possible here at Veritas. Learn more about yourself and improve your life and the lives of those around you. The Veritas myGenome test sequences your entire genome and teaches you about various genetic aspects of your health.

Something that seemed like science fiction only a few decades ago is now a reality which is at your fingertips, providing you with access to valuable information and preventative and personalised medicine. 

This article is based on the original article written by Maria Moreno, Medical Science Liaison Manager at Veritas Intercontinental.

See all

Maybe you may be interested

Leave a comment

No comments yet

There are no comments on this post yet.