The human pangenome, the goal of 21st century medicine

In April of this year, it was finally possible to sequence it the missing 8% of the human genome. Thus, after two decades, the first draft genome, published in February 2001, was completed. This milestone achieved by Telomere to Telomere (T2T) Consortium, a name used to refer to the fact that chromosomes were examined end to end, human DNA was found to contain a total of 20,465 genes which provide very valuable information about human evolution or genetic diseases.

Within the human genome there is a central part which is common to all humans and which is essential for the development of the human being, and a small percentage of variable part. This small percentage may hold information about how some patients respond better than others to treatment or why they are more prone to other diseases. It may also influence how exposure to various external factors, such as lifestyle habits, affects the onset of cardiovascular and metabolic pathologies. “Genetics is an important element in the genesis of diseases that we still do not fully understand, in their pathogenesis or to achieve effective treatment of various diseases such as cancer,” he tells about Dr. Encarna Guillen, Head of the Medical Genetics Section of the Virgen de la Arrixaca University Clinical Hospital in Murcia and President of the Spanish Association of Human Genetics (AEGH).

Accessing this part of the human genome is not easy. Our genome is a very long sequence of genes with 50% repetitive regions. Advances in technology have allowed us to sequence the first human genomes, also allowing us to briefly search for the mutated gene in a person that may cause a genetic disease such as Fabry or Wolf-Hirschhorn syndrome, but not allowing us to sequence each individual patient’s genome . This is where pangenomean accumulation of many human genomes of different ethnicities, places of birth, gender or age, which sheds light on this variable percentage.

“It is necessary to detect this variability and analyze the genomes of a wide variety of people”

The pangenome is the complete set of genes within a species. The first idea of ​​a pangenome appeared in 2005, when it was decided to sequence the genome of six strains of the bacterium streptococcus agalactiae. This species was found to have 80% core genome and 20% variable. This was the initial signal for the elucidation of the pangenome of many more species than bacteria. For example, the pangenome of fungi aspergillus fumigatus, reason every year from 300,000 serious human infections, reveals that each individual of the species has a different genetic content, a total of one-third of its genome is variable. This part is the cause of some of the infections and causes a different response to treatment, according to research published in Nature Microbiology.

One of those pangenomes being studied is that of the human being. “The complete human genome sequence contains information about 20 people, most of whom are Caucasian, but 70% of this information is from one individual,” explains Dr. Gillen. Therefore, this first genome lacks much information about the human beings currently inhabiting the Earth. “It is necessary to detect this variability and analyze the genomes of a wide variety of people. This is why the pangenome is made, with the genomes of 350 people which will be shared to obtain all possible information’.


The National Human Genome Research Institute (NHGRI) has el Human Pangenome Reference Center (HPRC) involved in the development of a human pan-genome. It has been found through various studies that 50% of the sequence is repeated and that there are gene-rich regions that vary by hundreds of kilobase pairs. Our DNA is constantly mutating. “Our instructional code consists of four bases that combine, resulting in protein coding. The change can change their expression or the way a disease manifests itself or how it responds to treatment,” points out Dr. Encarna Guillén.

“This will be an important genetic resource for future biomedical research and precision medicine”

HPRC research published in the journal Sciencie has identified little-studied variable genes that are related to cardiovascular diseases in African-American patients. Another study, published in the journal eLife, looks at how the nucleotide modifications of RNA and DNA change particularly resistant to changes caused by environmental or other genetic factors. In addition, efforts are being made to improve access to information and sequencing technology.

“The reference human pangenome will contain a more accurate and diverse representation of global genomic variation. This will make it possible to improve research on the relationship between genetics, diseases and populations. It will also extend the scope of genomic research to the most repetitive and polymorphic regions of the genome. Ultimately, this will be an important genetic resource for future biomedical research and precision medicine,” HPRC researchers say.

“Today we have a lot of information that allows us to work with different genetic diseases, many of them rare, or with complex diseases such as metabolic ones. This information will allow us to go further. Genetics is present throughout the health care system, and it is necessary for this 21st century medicine to continue to advance, be accessible, and be incorporated into the health care system,” concludes Dr. Gillen, referring to the fact that the specialty of clinical genetics continues without to be recognized in our country.

Because health we all need…

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