Arxiu de la categoria: GENETICS

What is gene therapy?

In the last years we have heard discuss gene therapy and its potential. However, do we know what gene therapy is? In this article, I want to make known this promising tool that can cure some diseases that therapies with conventional drugs cannot it. I discuss approaches of gene therapy and their key aspects, where we find animal models.


A clinical trial is an experimental study realized in patients and healthy subjects with the goal to evaluate the efficiency and/or security of one or various therapeutics procedures and, also, to know the effects produced in the human organism.

Since the first human trial in 1990, gene therapy has generated great expectations in society. After over 20 years, there are a lot of gene therapy protocols have reached the clinical stage.

Before applying gene therapy in humans it is necessary to do preclinical studies; these are in vitro or in vivo investigations before moving to clinical trials with humans. The aim of these is protect humans of toxic effects that the studied drug may have.

An important element in preclinical studies are animal models. First, tests are made with small animals like mice. If they are successful, then tests are made with larger animals, like dogs. Finally, if these studies give good results then they are passed to higher animals: primates or humans.


Gene therapy represents a promising tool to cure some of those diseases that conventional drug therapies cannot. This therapy consists in the transfer of genetic material into cells or tissues to prevent or cure a disease.

Initially gene therapy was established to treat patients with hereditary diseases caused by single gene defects, but now, at present, many gene therapy efforts are also focused on curing polygenic or non-inherited diseases with high prevalence (Video 1).

Video 1. Explanation about what gene therapy is (Source: YouTube)


There are two types of approaches in gene therapy (Figure 1):

  • In vivo gene therapy: introduce a therapeutic gene into a vector which then is administered directly to the patient. The vector will transfer the gene of interest in the target tissue to produce the therapeutic protein.
  • Ex vivo gene therapy: transfer the vector carrying the therapeutic gene into cultured cells from the patient. After, these genetically engineered cells are reintroduced to the patients where they now express the therapeutic protein.
Figure 1. Differences between the two types of approaches in gene therapy (Source: CliniGene – Gene Therapy European Network)


When designing a gene therapy approach there are some key aspects to be considered:


The gene of interest is that which is introduced into the body to counteract the disease. For the one hand, for the diseases are caused by the lost or dysfunction of a single protein, the gene to be transferred is more identifiable, being that only a correct copy of the gene whose dysfunction causes the diseases will be introduced. For the other hand, for the diseases whose origin is more complex the choice of the therapeutic gene may be more difficult and will have to make several studies and know well the disease.


Vehicle by which the gene of interest is transported to the target cells. The perfect vector should be able to transduce target cells without activating an immune response either against itself or the therapeutic gene. But there aren’t a universal vector to treat any disease.


These type of vectors derives from viruses, but this is not a problem because much or all of the viral genes are replaced by the therapeutic gene. This means that the viral vectors do not cause pathogenic disease because the gene was deleted.


These type of vectors does not derive from viruses, but the therapeutic gene is part of a plasmid.


Any cell that has a specific receptor for an antigen or antibody, or hormone or drug… The therapeutic gene must be directed to target cells in specific tissues.


The therapeutic gene must be administered through the most appropriate route. The type of route depends, as like as vector, the target tissue, the organ to manipulate or the disease to be treated.


Are used to find out what happens in a living organism. They are mainly used in research to achieve progress of scientific knowledge, as many basic cellular processes are the same in all animals and can understand what happens to the body when it has a defect; as models for the study of a disease, because humans and animals share many diseases and how to respond to the immune system; to develop and test potential methods of treatment, being an essential part of applying biological research to real medical problems and allowing the identification of new targets for the intervention of the disease; and, finally, to protect the safety of people, animals and environment, researchers have measured the effects of beneficial and harmful compound on an organism, identifying possible problems and determine the dose administration.

Gene therapy represents a promising tool to cure some of those diseases that conventional drug therapies cannot. The availability of animal models is key to preclinical phases because it allows thorough evaluation of safety and efficacy of gene therapy protocols prior to any human clinical trials.

In the near future, gene therapy will be an effective alternative to pharmacological efforts, and enable treatment of many diseases that are refractory or not suitable for pharmacologic treatment alone. Thus, gene therapy is a therapeutic tool that gives us virtually unlimited possibilities to develop better and more effective therapies for previously incurable diseases.



Sequencing the human genome

Genomics is a new science which has had a very important boom in recent years, thanks to advanced technologies of DNA sequencing, advances in bioinformatics and increasingly sophisticated techniques for analysing whole genomes. And I will discuss in this article about whole genomes and their sequencing, mentioning the Human Genome Project, which allowed the sequencing of the human genome.


Sequencing is the set of methods and biochemical techniques aimed at determining the order of nucleotides (A, T, C and G). Its objective is to get in order all nucleotides DNA of an organism.

The first organisms sequenced were two bacteria, Haemophilus influenzae and Mycoplasma genitalium in 1995. One year later, the genome of a fungus was sequenced (Saccharomyces cerevisiae).

From that moment comes the eukaryotic sequencing project: in 1998 Caenorhabditis elegans (nematode) was sequenced, in 2000 Drosophila melanogaster (fruit fly) and in 2001 the human genome.

But, why we sequenced? In the case of human genome, there is the need to know to help alleviate or prevent diseases.

Some of the organisms sequenced are model organisms, which have:

  • Medical importance: there are pathogens and we know diseases that they can cause.
  • Economic importance: organisms that humans eat, they can improve with the molecular techniques.
  • Study of evolution: in 2007 more than 11 species of Drosophila were sequenced and it tried to understand the evolutionary relationship between their chromosomes. It has also been made in mammals (ENCORE Project).


The human genome has 46 chromosomes, it means 23 chromosome pairs (22 autosomal chromosome pairs and 1 sexual chromosome pair, XX or XY depending if it is female or male).

The size of the human genome sequenced is 32,000Mb, 23 chromosomes plus Y chromosome.

The human genome was obtained from the mixture of human genomes to obtain a representation of all humanity genome.


A paradox is a statement that, despite apparently sound reasoning from true premises, leads to a self-contradictory or a logically unacceptable conclusion. In genomes we find two clear paradoxes.

The first one refers to the C-value, which represents the amount of DNA in the genome. As would be expected, if the organism is larger and more complex, the size of its genome will be bigger. However this is not true because there is not this correlation. It is due because the genome not only contains coding genome and proteins, but also contains repetitive DNA. In addition, the most compacted genomes are found in organisms less complexes.

The second paradox refers to the G-value, which represents the number of genes. There is no correlation between the number of genes and its complexity. A clear example is that in human genome has around 20,000 genes and Arabidopsis thaliana (herbaceous plant) has 25,000 genes. The reason is found in the RNA world, which is more complex and it is related to gene regulation.


The human genome sequencing project has been the most important biomedical research project of the whole history. With a budget of 3 thousand millions of dollars and the participation of an International Public Consortium, which was formed by EEUU, UK, Japan, France, Germany, China and other countries. Its ultimate objective was achieving the complete sequence of the human genome.

It started in 1990, but things get complicated when, in 1999, appeared a private company, Celera Genomics, headed by the scientist Craig J. Venter, who launched the challenge of getting the human sequence in record time, before the expected by the Public Consortium.

At the end it was decided to leave in a draw. The Public Consortium accelerated the process and obtained the draft almost at the same time. On 26th June 2000, in a ceremony at the White House with President Bill Clinton, the two leading representatives of the parties in competition, Craig Venter by Celera and the Public Consortium director, Francis Collins found. It announced the achievement of two drafts of the complete human genome sequence (Video 1). It was a historic moment, as the discovery of the double helix or the first time the man went to the Moon.

Video 1. Human Genome announcement at the White House (Source: YouTube)

The corresponding publications of both sequences did not appear until February 2001. The Public Consortium published its sequence in the journal Nature, while Celera did in Science (Figure 1). Three years later, in 2004, the Consortium published the final or complete version of the human genome.

Figure 1. Covers publications of the human genome sequence draft in Nature and Science magazines in February 2001 (Source: Bioinformática UAB)


The genome of the year 2001 is the reference genome. From here we have entered in the era of personal genomes, with names and surnames. Craig Venter was the first person who sequenced his genome, and the next one was James Watson, one of the discoverers of double helix.

It took 13 years to sequence the reference genome. It took less time to sequence Craig Venter’s genome and only few months for Watson’s genome.


Without going to sequence the entire genome they have been identified disease-causing genes. An exome is not the whole genome, but the part of the genome corresponding to exons.

An example is the case of Nicholas Volker (Figure 2), the first case of genomic medicine. This child had a severe and intractable inflammatory bowel disease of unknown cause. With exome sequencing was allowed to discover a mutation in the XIAP gene on chromosome X, replacing an amino acid functionally important for another. A bone marrow transplant saved the life of the patient.

nicholas volker
Figure 2. Nicholas Volker with his book One in a Billion, which tells his story (Source: Rare & Undiagnosed Network)


  • L. Pray. Eukaryotic genome complexity. Nature Education 2008; 1(1):96
  •  Brown. Genomes 3, 3rd edition (2007)
  • Bioinformática UAB
  • E. A. Worthey et al. Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genetics in Medicine 2011; 13, 255-262
  • Main picture: Noticias InterBusca


Hybrids and sperm thieves: amphibian kleptons

In biology a hybrid is the result of the reproduction of two parents of genetically different species, although in most cases hybrids are either unviable or sterile. Yet in some species of amphibians, sometimes hybrids are not only viable, but also become new species with special characteristics. In this entry we’ll show you two cases of amphibian hybrids that form what is known as a klepton and that make the definition of species a little less clear.


A klepton (abbreviated kl.) is a species which requires another species to complete its reproductive cycle. The origin of the word klepton comes from the Greek word “kleptein” which means “to steal”, as the klepton “steals” from the other species to reproduce. In the case of amphibians, kleptons have originated from hybridation phenomena. The amphibian’s potent sexual pheromones and the multispecies choirs in the case of anurans, causes some males and females of different species to try to mate together. Yet hybrids are only viable between closely related species.

Among the different klepton species we can encounter two different methods depending on the type of conception: zygokleptons, in which there’s fusion between the egg and the sperm’s genetic material, and gynokleptons, in which the egg needs the stimulation from the sperm but doesn’t include its genetic material.

The different amphibian kleptons are usually constituted entirely by females (there are usually few or no males) that use the sperm of another species to perpetuate the klepton. As some kleptons depend on various related species, this can promote the creation of “species complexes” in which various similar species present hybridization areas and very complicated relationships among them. Below you’ll find two klepton examples, one in European anurans and the other in American urodeles.


The European water frogs (Pelophylax genus) form what is known as a “hybridogenetic complex” in which the hybrids from different species form kleptons which can’t reproduce among each other but, which must reproduce with a member of one of the parental species, “stealing” or “parasitizing” its sperm in order to survive.

Photo by Bartosz Cuber of two edible frogs (Pelophylax kl. esculentus) in amplexus. This is the best known hybrid both because of its wide distribution, and for being considered a delicacy in France.

In the hybridogenesis of water frogs the genetic material of both parents combines to form the resulting hybrid (zygoklepton). This hybrids (almost always females) will have half their genome from one species and half from the other. Yet, not being able to reproduce with a similar hybrid, during gametogenesis the hybrids eliminate the genetic material from one of the parent species. This way, when reproducing with an individual from the species whose genetic material has been deleted, they will form another hybrid.

Scheme of the genetic composition of the different Pelophylax kleptons. In this hybridogenetic complex four “natural” species intervene: the marsh frog (Pelophylax ridibundus, RR genome), the pool frog (Pelophylax lessonae, LL genome), the Iberian waterfrog (Pelophylax perezi, PP genome)  and the Italian pool frog (Pelophylax bergeri, BB genome).

The edible frog (Pelophylax kl. esculentus, RL genome) comes from the hybridization between the marsh frog and the pool frog. The Italian edible frog (Pelophylax kl. hispanicus, RB genome) stems from a hybrid between the marsh frog and the Italian pool frog. Finally, the Graf’s hybrid frog (Pelophylax kl. grafi, RP genome) originated from the hybridization between the edible frog (in which the DNA of the pool frog is eliminated from their gametes) and the Iberian waterfrog.

Schemes by Darekk2 of the hybridogenetic processes in the different European water frog’s kleptons. The bigger circles represent the individual’s genome and the smaller circles the gametes’ genetic material.

As we can see, the genetic information of the marsh frog is the only one present in all three kleptons. These kleptons delete the genetic material of the species with which they share their habitat from their gametes but keep the genetic material of the marsh frog (R). So for example, the edible frog (P. kl esculentus) deletes form its eggs the DNA of the pool frog (L) with which it encounters and breeds in its natural range, resulting in more edible frogs (RL). The marsh frog seldom reproduces with some of its hybrids and if it does, they produce normal marsh frogs.


The salamanders of the Ambystoma genus, usually known as mole salamanders, are a genus endemic of North America and are the only living representatives of the Ambystomatidae family. Five of these species form what is known as the “Ambystoma complex”, in which these species contribute to the genetic composition of a unisexual lineage of salamanders which reproduce by gynogenesis (gynoklepton). Based on the mitochondrial DNA of the unisexual populations, it is thought that this complex originated from a hybridization event of about 2.4-3.9 million years ago.

ambystomert complexx
This complex consists of the five following species: the blue-spotted salamander (Ambystoma laterale LL genome, photo by Fyn Kynd Photography), the Jefferson salamander (Ambystoma jeffersonianum JJ genome, photo by Vermont Biology), the small-mouthed salamander (Ambystoma texanum TT genome, photo by Greg Schechter), the streamside salamander (Ambystoma barbouri BB genome, photo by Michael Anderson) and the tiger salamander (Ambystoma tigrinum TiTi genome, photo by Carla Isabel Ribeiro).

In the gynogenesis of this all-female lineage, the egg needs activation by a sperm to start division and development but, it first has to duplicate its genetic material by endomitosis to avoid the formation of an unviable haploid (with half the genetic information) zygote. Yet, as in parthenogenetic reptiles, in the long term the lack of genetic recombination can take its toll on the individuals. That’s why this lineage of unisexual salamanders has the capacity of occasionally incorporating the whole genome from the males of four of the species which constitute the complex (currently the reproduction of streamside salamanders with members of the unisexual lineage hasn’t been documented).

Scheme from Bi, Bogart & Fu (2009) in which we can see the different paths that the gynogenetic mole salamanders can take while reproducing.

These individuals don’t mix the newly acquired genome, they add it. Therefore, among the members of this lineage we can find diploid, triploid, tetraploid and even pentaploid individuals (even if as the ploidy increases the individuals are less apt to survive) depending on how many different genomes the previous generations had incorporated.

mes ibrids
Among the klepton, the most common genome combination is that of triploids based on the blue-spotted salamander and the Jefferson salamander, with the genomes LLJ (left, image by David Misfud) and JJL (right, image by Nick Scobel), even though the number of combinations is incredibly large. For this reason why scientists haven’t been able to decide a valid scientific name for this group of hybrid origins.

Unlike the water frogs, it is very difficult to define a scientific name for the klepton inside Ambystoma, as the genomes of the different species can be found in different combinations and proportions in different unisexual individuals.


The following sources have been consulted during the elaboration of this entry:


Marfan syndrome: how to live of a rare disease

What they have in common the American president Abraham Lincoln, the Greek painter El Greco or the Spanish actor Javier Botet? All of them had or have Marfan syndrome. This is included within rare diseases (less of 1 case per 2,000 inhabitants). In this article I will explain what happens to people who suffer Marfan syndrome, and also one example of people affected and how he has taken advantage of his syndrome.


Marfan syndrome is a rare disease of the connective tissue, it means the tissue that spreads throughout the body and its mission is to join the tissues, fill the gaps between organs…The connective tissue is found in all the body, and the Marfan syndrome’s patients have various problems in multiple organs (bones, eyes, heart, blood vessels, nervous system, skin and lungs).

Its name comes from the French doctor Bernard Jean Antoine Marfan that, in 1896, detected the case of a 5-year-old girl who had disproportionate long arms in relation to her body and finger very thin and long.

It is included within rare diseases because it affects 1 in 5,000 people. A rare disease is one that affects a small number of people compared to the general population.


The clinical features can be grouped mainly in skeletal system, cardiovascular system and ocular system.

The characteristics of the skeletal system are the most visual and among them we find (Figure 1):

  • Dolichostenomelia: disproportionality long extremities in comparison with the length of the trunk. It implies that people are taller than would be expected from their genetic background.
  • Arachnodactyly: thin and long fingers, like spider’s legs.
  • A high, arched palate and crowded teeth.
  • Scoliosis: an abnormally curved spine (S or C).
  • A breastbone that protrudes outward (pectus carinatum) or dips inward (pectus excavatum).
fig caract
Figure 1. A Marfan syndrome’s boy, where we can see pectus excavatum, dolichostenomelia and arachnodactyly (Source: National Marfan Foundation)

The features of cardiovascular system are the main source of morbidity and early mortality. Dilatation of aortic artery is the most common and serious, but also we find tear and rupture of the aorta, mitral or tricuspid valve prolapse…

Finally, within ocular system we have ectopia lentis (a displacement or malposition of the eye’s crystalline lens from its normal location) or myopia. There is also a high risk of retinal detachment, glaucoma and early onset of cataracts.


Marfan syndrome is caused by a change in the gene that controls how the body makes fibrillin (FBN1), an essential component of connective tissue that contributes to its strength and elasticity. This gene is located in chromosome 15 and the severity of the disease depends on the affected part. It means that there aren’t two identical types of Marfan. There are some people who have physical traits more pronounced, and this facilitates the diagnosis. But there are other people that who do not show outward signs.

It has an autosomal dominant inheritance; it means that an altered allele is dominant over the normal allele and it only needs a copy for expressing the disease. It appears in all generations and a child of an affected parent has a 50% probability of suffering this syndrome. However, it can also occur by de novo mutations in the gene FBN1 (spontaneous mutations). The probability of these mutations is low and it is presented in 25% of all cases of Marfan syndrome.


As in most rare diseases there is no treatment, but it can alleviate pain and symptoms caused by the syndrome.

Complications have to anticipate and prevent. The treatment is to act on the cardiovascular effects, mainly to avoid the risk of dilating the aorta.

Doctors do regular cardiological tests, repair or replace large vessels, replace of heart valve, do rehabilitation and orthopedic tests to minimize scoliosis and avoid contact sport.


Throughout history many famous personalities have suffered Marfan syndrome. The tendency of painting elongated humans of Dómenikos Theotokópoulos “El Greco” was due to Marfan syndrome. But it is not the only case known, the musician Niccolò Paganini or the member of the band The Ramones, Joe Ramone, also had it.

Depending on the genetic disease that people suffer, it can be difficult to live with it. But there are some people who have managed to take advantage of it.

This is the case of the Spanish actor Javier Botet. He is known for his role as the Medeiros’ girl in Rec (Jaume Balagueró and Paco Plaza) or mom in Mamá (Andrés Muschietti), among others. His case is complicated, because he has undergone surgery five times. He has taken advantage of his appearance and physical characteristics to characterize diabolic characters (Video 1, not suitable for sensitive people!).

Video 1. Movement test of Javier Botet in Mamá (Source: YouTube)

The example of this guy shows us that we must always see the glass half full and turn the situation around.



How is genetic engineering done in plants?

For years, by crossing, scientists have achieved plants with a desired characteristic after many generations. Biotechnology accelerates this process and allows to catch only the desired genes from a plant, achieving the expected results in only one generation. Genetic engineering allows us to do all this. In this article I will explain what it is and how does it work.


Genetic engineering is a branch of biotechnology that consists in modifying hereditary characteristics of an organism by altering its genetic material. Usually it is used to get that certain microorganisms, such as bacteria or viruses, increase the synthesis of compounds, form new compounds or adapt to different environment.

It is a safer and more efficient tool for improving species than traditional methods (crossing) as it eliminates much of the randomness. On the other hand, modern biotechnology also becomes a new technology that has the power to modify the attributes of living organisms by introducing genetic material prepared in vitro.

It could be defined as the set of methodologies to transfer genes from one organism to another and express them (to produce proteins for which these genes encode) in different organisms of the original organism. DNA which combines fragments of different organisms is called recombinant DNA. Consequently, genetic engineering’s techniques are called recombinant DNA techniques.

Currently there are more plant organisms genetically modified than animal organisms. For this reason I will explain genetic engineering based on plants.


This methodology has 3 key advantages compared with traditional methods of genetic improvement based on hybridization:

  • The genes could come from any specie (for example a bacteria’s gene can be incorporated in soy‘s genome).
  • At genetically improved plant you may introduce a single new gene preserving the remaining genes from the original plant to their offspring.
  • This modification process delays less the deadlines than improvement by crossbreeding.

With this way you can modify properties of plants more broadly, more accurate and faster.

In traditional crossing it generates a hybrid which combines randomly genes of both parental organisms, including the gene of interest encoding the desired trait. In contrast, biotechnology techniques only pass one or few genes which encode a specific trait known. The new plant has all the original genes of the plant and an introduced gene accurately and directed (Figure 1).

Figure 1. (A) Traditional method where, by crossing, a new variety is obtained. This carries the gene of interest (red), but also another genes randomly. (B) With genetic engineering we obtain a new variety of commercial plant with the gene of interest (red) of any other species (Source: Mireia Ramos, All You Need is Biology)


Obtaining a transgenic organism through genetic engineering techniques involves the participation of an organism who gives the gene of interest and a receptor organism who will express the desired quality. The steps and the process techniques are:



This technique is to remove the expression of a gene, replacing it with a mutated version of itself, this being a non-functional copy. It allows the gene is not expressed.


It is the opposite of the knock out process. A gene is replaced by a modified version of itself, which produces a variation in the resulting function of it.

In medicine, the knock in technique has been used as a strategy to replace or mutate genes that cause diseases such as Huntington’s chorea, in order to create a successful therapy.


Firstly, you have to check the characteristic of interest comes from a gene, as this will be easier to transfer to a living organism that does not.


It is a complex process, but outline the steps are the following:

  • Extract DNA
  • Find a gene among the genes of this DNA
  • Sequence it
  • Build the recombinant vector

The DNA of interest is inserted into a plasmid, a circular DNA molecule with autonomous replication. The plasmids of bacterial origin are the most used (Video 1).

Video 1. “Clonación de un gen en un plásmido vector”. Explaining the use of plasmids as a vector in the process of cloning (Source: YouTube)

The development of these techniques was possible by the discovery of restriction enzymes. These enzymes recognize specific sequences and cut the DNA by these points. The generated ends can be sealed with ligase enzyme and to obtain a new DNA molecule, it called recombinant DNA (Figure 2).

Figure 2. (1) Plasmid’s DNA (2) DNA from another living organism (3a, 3b) The restriction enzyme cuts DNA (4) The restriction enzyme recognizes AATT sequence and cuts between A and T nucleotides (5) The two DNAs are contacted with the purpose of forming recombinant molecules (6) A ligase enzyme joins the DNA ends (Source: GeoPaloma)


If we know the gene sequence we can compare this sequence with known gene sequence through bioinformatics, provided to determine which gene looks and assign a possible function. So when we have predicted the function of cloned gene we confirm it in vivo, usually transferring it to a model organism.


We can add (promoter, introns…) or mutate sequences inside the encoding region.


When we have finished the gene building with the desired gene and the promoter, the recombinant DNA is inserted into the cells of the living organism that we want to modify.


When we already have the GMO (Genetically Modified Organism) it is analysed from the molecular and biological point. In the molecular analysis it must demonstrate if you have one or more copies of the transgene or how and what tissues the gene is expressed. In the biological analysis it looks if it achieves the objective for which it was designed.



Nutritional genomics: À la carte menu

When Hipprocrates said “let food be your medicine and medicine be your food” he knew that food influences our health. And it tells us that nutritional genomics, which I will discuss in this article; a new science appeared in the post genomic era as a result of the sequencing of human genome (all DNA sequences that characterize an individual) and the technological advances that allow the analysis of large amounts of complex information.   


The aim of nutritional genomics is to study the interactions of genes with elements of the human diet, altering cellular metabolism and generating changes in the metabolic profiles that may be associated with susceptibility and risk of developing diseases.

This study wants to improve the health and to prevent diseases based on changes in nutrition. It is very important not understand nutritional genomics how that specific food or nutrients cause a particular answer to certain genes.

When we talk about diet we have to distinguish between what are nutrients and what are food. Nutrients are compounds that form part of our body, while foods are what we eat. Food can take many nutrients or only one (such as salt).


Within nutritional genomics we find nutrigenomics and nutrigenetics, but although their names we may seem to mean the same is not the case (Figure 1).

Nutrigenomics is the study of how foods affect our genes, and nutrigenetics is the study of how individual genetic differences can affect the way we respond to nutrients in the foods we eat.

Figure 1. Schematic representation of the difference between nutrigenomics and nutrigenetics (Source: Mireia Ramos, All You Need is Biology)


Nutrients can affect metabolic pathways and homeostasis (balance) of our body. If this balance is disturbed chronic diseases or cancer may appear, but it can also happen that a disease, which we have it, be more or less severe. It means that impaired balance can give the appearance, progression or severity of diseases.

The aim of nutrigenomics is that homeostasis is not broken and to discover the optimal diet within a range of nutritional alternatives.

Thus, it avoids alterations in genome, in epigenome and/or in expression of genes.


Free radicals are subproducts that oxidise lipids, proteins or DNA. These can be generated in mitochondria, organelles that we have inside cells and produce energy; but we can also incorporate from external agents (tobacco, alcohol, food, chemicals, radiation).

In adequate amounts they provide us benefits, but too much free radicals are toxic (they can cause death of our cells).

Antioxidants neutralize free radicals. But where can we get these antioxidants? There are foods that contain them, as Table 1 shows.

Table 1. Example of antioxidants and some foods where we can find them (Source: ZonaDiet)

The way we cook food or cooking is important for avoid to generate free radicals. In barbecues, when we put the meat on high heat, fats and meat juices fall causing fire flames. This produces more flame and it generates PAHs (a type of free radicals). These adhere to the surface of the meat and when we eat it can damage our DNA.


Epigenome is the global epigenetic information of an organism, ie, changes in gene expression that are inheritable, but they are not due to a change in DNA sequence.

Epigenetic changes may depend on diet, aging or drugs. These changes would not have to exist lead to diseases as cancer, autoimmune diseases, diabetes…

For example, with hypomethylation, in general, cytosines would have to be methylated are not. What does it mean? Hypomethylation silenced genes and then, they cannot be expressed. Therefore, we need methylated DNA. A way of methylate DNA is eating food rich in folic acid.


There are agents (UV rays) that activate pathways that affect gene expression. Occurring a cascade that activates genes related to cell proliferation, no differentiation of cells and that cells survive when they should die. All this will lead us cancer.

It has been found that there are foods which, by its components, can counteract activation of these pathways, preventing signal transduction is given. For example curcumin (curry), EGCG (green tea) or resveratrol (red wine).



The fear of getting older

When we are children we look forward to the day of our birthday. That day is own, friends and family give us presents and we blow the candles hoping that all our wishes will fulfil. Over the years gifts decrease and we value that they remember us. But that special day is linked to the fear of getting older. In this article I will talk about what is aging and its genetics.


Rembrandt Harmensz van Rijn (1606 – 1669) was a Dutch painter and etcher. He is considered one of the greatest painters and printmakers in European art. He liked painting self-portraits (Figure 1). There are a lot of his self-portraits and we can look the course of time in his face and his aging.

Figure 1. Self-portraits by Rembrandt (Source: El Mundo)

We relate the word aging with the verb gain (gain experience, gain weight, gain wrinkles) and the verb lose (lose hair, lose loved ones, lose abilities). But what is aging?

Aging is a process that there is a deterioration of homeostatic mechanisms. Homeostasis is a system in which variables are regulated so that internal conditions remain stable and relatively constant (pH, oxygen pressure…). All organs and systems of our body are part of homeostatic mechanisms.

Then, as we age, in our organism the following occurs: decrease the organic functions, as with the stomach, which works worse and it is more difficult to digest; and it is more difficult to adapt, most old people are more easily dehydrated. All this is linked to a tissue atrophy and decrease cell turnover, since the balance between cells that form and cells that are destroyed is lost with age.

Aging is a physiological process, not a disease, although in this physiological situation there is more pathological events.


Sometimes when we talk about aging is easily confused with the term senescence. Aging refers to the whole body, while senescence is the aging process at the cellular and organic part.

When a cell suffer a senescent stimulus occurs an arrest cell cycle and DNA damage. It means that cell stops growing because its DNA is damaged. The diminution of cellular proliferation, for example in bone marrow it can cause anaemia.

Tissue cells can enter senescence due to UV radiation and a series of proteins are generated, activating macrophage recruitment of immune cells. These macrophage cells, as part of the immune system, are responsible for removing other harmful cell to the body. Then they kill senescent cells and leave holes, which are covered by new cells. This is what happens in normal skin.

If this process occurs in an old skin, some senescent cells can not die because there are not enough macrophages. Then the tissue will be thinned by their inability to form new cells.


There are a number of factors, including genetic and epigenetic factors that contribute to aging (Figure 2):

  1. Genomic instability: there has to be balance between DNA damage and repair pathways. It has to repair DNA to not have a senescent phenotype in the cell.
  2. Telomere attrition: they are the ends of chromosomes and will shorten after each cell division. When they are very short the cell dies.
  3. Epigenetic alterations: how environment influences in gene expression.
  4. Loss of proteostasis: changes in degradation capacity of proteasome, a complex which eliminates unneeded or damaged proteins.
  5. Deregulated nutrients sensing: the elderly do not control well their desire to eat, or they eat too much or they eat very little. They have not a good sensitivity to signals of satiety and appetite. The same applies to the sensation of thirst. The elders never thirst and this can cause dehydration.
  6. Mitochondrial dysfunction: mitochondria provide energy for cellular activity.
  7. Cellular senescence: cell damage processes occur.
  8. Stem cell exhaustion: stem cell formation decreases. In muscle cells there are not new cells to repair muscle fibres and muscle is becoming smaller, causing the person is getting weaker.
  9. Altered intercellular communication: different cellular pathways do not work well.
hallmarks aging
Figure 2. The 9 hallmarks of aging (Source: The Hallmarks of Aging)

You can propose a number of alternatives or interventions in each of the above factors that could lengthen the average life of the organism, but still not have the tools necessary to assess all factors that may be involved in aging, although much has been achieved in recent years.

However, the interpretation of what is pathological and what is not supposed one of the main challenges to solve.


  • F. Rodier, J. J. Campisi. Four faces of cellular senescence. Cell Biol. 2011; 192(4), 547-56
  • Daniel Muñoz-Espín, Manuel Serrano. Cellular senescence: from physiology to pathology. Nat. Rev. Molecular Cell Biology 2014; 15, 482-496
  • C. López-Otin, M. A. Blasco, L. Partridge, M. Serrano, G. Kroemer. The Hallmarks of Aging. Cell 2013


21st March: world Down syndrome day

21st March is the World Down Syndrome Day. This syndrome is a chromosomal combination that has always been part of the human condition. It exists in all regions of the world, and usually it has variable effects on learning styles, physical characteristics or health. It affects 1 in 700 children, making it the most common chromosomal abnormality and the first cause of mental disability. With this article I want to introduce a little more this syndrome.


Its name comes from the English doctor John Langdon Down who described a group of patients with intellectual disabilities and similar physical characteristics, in 1866. These patients had Down syndrome.

However, already existed artworks with people with Down syndrome (Figure 1), but Langdon Down was the first one to group them in a subcategory within individual with cognitive impairment.

quadre oli
Figure 1. “The Adoration of the Christ Child” (1515). This oil painting, made by a follower of Jan Joest van Kalkar, shows two people with Down syndrome (Source: Arte y síndrome de Down)

It is called syndrome because the affected people express a known set of symptoms or signs that they may appear together, although its origin is unknown. Even though physical features are common, each person with Down syndrome is a unique individual and can present the characteristics in different degrees or not.


  • Diminished muscle tone
  • Small ears
  • Slanting eyes
  • Short nose
  • Flat back of head
  • Single crease in the palm of the hand: simian crease: complete fusion between heart line and headline (Figure 2)
  • Tendency to obesity
Figure 2. (1) Common lines, like M, and (2) simian crease, complete fusion between heart line and headline (Source: Incidencia de nacimientos pretérmino y de término con peso bajo al nacer y existencia de línea Sydney)

When they are children present retardation in reaching capabilities as sitting independently, wandering, first words…


In 1959, Jérôme Lejeune, a French doctor, saw that people with Down syndrome had 47 chromosomes in each cell instead of 46. This extra chromosome was 21 (Figure 3). The article  Why I look similar to my parents? reminds us what a chromosome is.

Figure 3. Male karyotype, person with Down syndrome (Source: Mireia Ramos, Cerba Internacional SAE)

So, Down syndrome or trisomy 21, is a result of an extra chromosome. But having and extra copy of chromosome 21 can be given by three phenomena.


It is the major cause and represents 95% of cases. It is produced by an error in the process of cell division. It means that when parent’s cell divides there is an error, and the son inherits two copies of chromosome 21 instead of one.

Then the son has 3 chromosomes 21: 1 comes from one parent and 2 come from the other parent, which are transmitted together.


During the process of cell division of one parent, a chromosome 21 joins with other chromosome, usually a chromosome 14.

Then the son has 3 chromosomes 21: one comes from one parent and two come from the other parent.

It represents 4% of cases, and it is important to identify it to avoid passing the translocation to another child, if the couple wants another child.


It is the least common cause because it represents 1% of cases. After fertilization nondisjunction occurs, but not in all cells. This causes cells with 46 chromosomes and cells with 47, forming a mosaic.

Cells with 47 chromosomes have an extra chromosome 21.


It has been found that the age of the mother is related to have a child with Down syndrome, i.e., the risk of having a baby with Down syndrome is greater among mother age 35 and older.

Trisomy 21 is the most trisomy accepted by nature, so in pregnancy test doctors always study it. If they detect a foetus has Down syndrome, the couple can choose to go ahead or to stop pregnancy.

People with Down syndrome are increasingly integrated into our society. Their IQ is 45-48, when the standard range is around 100, but with a special school integration support is highly beneficial and IQ can go up to 70.

Nowadays, more and more companies offering workplaces for them and this should not surprise us, because after all they only have an extra chromosome (Figure 4).

Figure 4. Keep calm it’s only and extra chromosome (Source: Pinterest)




“I am your father… or not”

Do you remember what Darth Vader told to Luke Skywalker? Well, in Spain, more 25% of cases about paternity tests cannot tell it. As the saying goes: “children of my daughter, my grandchildren will be; but children of my son, I don’t know”. In this article I am going to talk about paternity tests and their evolution.


The objective of paternity tests is prove whether two individuals are biologically parent and child.

There are many reasons to want to do a paternity test (Figure 1), either for personal purposes as legal, such as causes of filiation (to know who is your father), challenging results, unrecognized children…

Figure 1. Doubts about paternity (Source: Infogen)

Time ago women claim these test, but nowadays there are many men who request them to avoid pay maintenance after a divorce or infidelity.


The argument about who is the father of an individual is not recent, we find paternity disputes record on time of Roman Empire.

The methods to solve these disputes have changed. Firstly, the tests were bases on the physical appearance. It is true that behind the resemblances there is inheritance, but the ignorance of the transmission mechanism little objectivity when comparing them were useless.

 At 20s, blood groups allowed exclude paternity. It means that if the child is blood type B, the father may not be A if mother is 0, as shown in Table 1. The blood group of the mother will do the blood group of the child, because we believe that the mother has given birth to the child and is therefore not questioned her motherhood.

taula grups sanguinis
Table 1. Determining blood groups of children according blood group of parents (Source: Mireia Ramos, All You Need is Biology)

Although blood group could exclude paternity, courts did not admit as an evidence time ago. It is what happened to Charlie Chaplin when Joan Barry accused him to be the father of her child. Blood test excluded Chaplin as a father because his blood type was different, but the court did not accept this test. Finally, Chaplin paid the maintenance of Barry’s child. This case promoted passing new laws and forensic tests.

chaplin judici
Figure 2. Trial of Chaplin and Barry (Source: GettyImages)

Nowadays paternity tests are based in a genetic study, with the objective to allow know if there is genetic relationship between father and child by the similarity that must exist between the two samples. So, it allows to confirm or to refuse paternity. But these test not only use to validate that legal father is biological father too.


The identification of individuals based on the study of DNA can be made from any biological sample (blood, buccal mucosa, hair, urine, teeth or even degraded organic material). This is the reason why this analysis is not only useful for the study of paternity and other kinship, but also used in forensic studies, historical research and anthropological studies.

DNA testing is done by analysing genome sequences highly variable, i.e., between individuals of a population may have different forms called alleles. What we analyse to determine paternity are what we call genetic polymorphisms, namely, that the people there are two or more ways (allelic variants) for a gene. These polymorphic variants are inherited and, therefore, the son will present a combination of certain polymorphisms that will be inherited from their parents.

In paternity we analyse repeat polymorphism, i.e., varies the number of times we have repeated the sequence. This sequence has an identifiable physical location and it calls genetic marker.

For each marker a person has two alleles, one comes from the mother and the other comes from the father. This combination of alleles that we receive from our parents is genotype.

To understand this better let’s look at Figure 3. The numbers under each individual display their genotype. This genotype is composed of two alleles, each allele indicates the number of repeats polymorphism.

Figure 3. Difference in the interpretation of a paternity test, where the supposed father and the child coincide (case A), respect a paternity exclusion (case B) (Source: DNAProfile)

Once we have the results for different markers analysed we proceed, finally, to determine paternity or not. If the supposed father is consistent with the child must do a study biostatistician to estimate the probability of paternity, namely, look how many men could randomly matched with the child. But if the supposed father and the child do not coincide we establish an exclusion, and the result is unquestionable.


  • Lorente J.A., Lorente M. El ADN y la identificación en la investigación criminal y en la paternidad biológica. Editorial Comares
  • E. Huguet, Á. Carracedo, M. Gené. Introducción a la investigación biològica de la paternidad. Promociones y publicaciones universitarias 1988
  • Infogen
  • Pruebas de paternidad: información básica
  • DNAProfile


Why I look similar to my parents?

The reason of the similitude with our parents is genetics. This science studies the inheritance; it means how offspring resemble their parents, the diseases that are transmitted from generation to generation… It is biology’s discipline growing quickly and it affects biology, healthy and society in general. In this article I am going to talk about what is genetics and the DNA’s discovery.


The genetic information is inherited to the offspring by genes, which are the storage unit of this information. They are located inside the chromosomes and they occupy specific positions. The number of chromosomes is constant inside species, but different between other species.

In humans the number of chromosomes is 46. In each cell we have 46 chromosomes, which 44 are autosomal, i.e., not a chromosome sexual and 2 chromosomes sexual. The total of 46 chromosomes is the human genome.

Our genome consist of 2 sets of 23 chromosomes counterparts. This means that each set have the same characteristics respect the other set and one comes from our mother by ovum and the other one comes from our father by sperm (Figure 1). Inherit each set of our progenitor is the reason why we resemble they, but also is via that we inherit some genetic diseases.

Figure 1. Human female karyotype, i.e., the graphical representation of chromosomes. They are placed in pairs sorted and size, from the largest to the pair smaller, plus the sex chromosomes (Source: Mireia Ramos, Cerba Internacional SAE)


Genes are parts of DNA (deoxyribonucleic acid), comprising by the join of small molecules that called nucleotide. These nucleotides contain a pentose (compound of 5 carbon), a phosphate and a nucleobase (organic compound with an atom of nitrogen) (Figure 2). There are 4 nucleobase: two purines (adenine and guanine) and two pyrimidines (thymine and cytosine). These nucleobases distinguish each nucleotide and their arrangement constitutes the genetic code.

Sin título1
Figure 2. Details of the chemistry of DNA (Source: Eduredes: Los ácidos nucleicos)

But all knowledge about DNA and genes is recent. The structure of DNA was discovered by James Watson and Francis Crick in 1953 in Cambridge (Figure 3). Previously, other scientists had done studies to try to determine the similarity between relatives, but it was not until this discovery it was understood that there was chemistry behind it.

Figure 3. Francis Crick (right) and James Watson (left) with the construction of the structure of DNA (Source: The DNA store)


Watson, an American 23 year-old biologist, and Crick, an English 35 year-old physicist, worked in the Cavendish Laboratory in Cambridge. They spent many months building models of molecules and comparing them to the information they had, but still they couldn’t find the correct structure of DNA.

In the King’s College of London, the physicist Maurice Wilkins and Rosalind Franklin, another physicist with knowledge in crystallography. She took X-ray pictures of DNA (Figure 4).

Figure 4. The four people who contributed to the discovery of DNA (Source: Biology: The people responsible for the discovery of DNA)

Watson and Crick, after present a wrong model of the triple helix, told Maurice Wilkins about what they were trying to do and he showed them a new and better X-ray picture of DNA, which had been taken by Rosalind Franklin, without her permission. This was the picture number 51 to help them solve the mystery (Figure 5).

photo 51 explanation
Figure 5. Explanation of picture 51 that used Watson and Crick (Source: Seguramente estaré equivocado: La “fotografía 51”)

When the university’s Cavendish Laboratory was still at its old site at nearby Free School Lane, the pub was a popular lunch destination for staff working there. Thus, it became the place where Francis Crick interrupted patrons’ lunchtime on 28th February 1953 to announce that he and James Watson had “discovered the secret of life” after they had come up with their proposal for the structure of DNA. This day is called for someone the 8th day of Creation.

The 25th April 1953 it published their article with 900 words in Nature (Figure 6). Three years earlier had published law Chargaff, which was one of the foundations to apply the theory of the double helix of DNA. This law establishes the complementarity of the bases in DNA, i.e., adenine (A) pairs with thymine (T) and the same with guanine (G) and cytosine (C) (Figure 2). So the amount of purine (A and G) is equal to the amount of the pyrimidine (T and C).

Figure 6. Article published in the journal Nature, which shows the picture 51 (Source: The DNA store)


It has been argued that the discovery of DNA as well as our understanding of its structure and function may well be the most important discovery of the last century. The effect of the discovery of DNA on scientific and medical progress has been enormous, whether it involves the identification of the genes that trigger major diseases or the creation and manufacture of drugs to treat these devastating diseases. In fact, the identification of these genes and their subsequent analysis in terms of therapeutic treatment has ultimately influenced science and will continue to do so in the future.

While the discovery of DNA has been a significant one in the twentieth century, it will continue to revolutionize medicine, agriculture, forensics, paternity and many other important fields in society today. DNA research encompasses an evolving area of progress and continued funding and interest in its relevance will likely fuel new discoveries in the future.