Arxiu d'etiquetes: translocation

From lab to big screen (I)

A little more than a month for the great gala of the cinema, the Oscars, I present some films related to genetics. There is a variety of feature films, especially sci-fi. For this reason, this is the first of several articles about cinema. In this article I will focus on films based on genetic diseases.

WONDER (2017)

Director: Stephen Chbosky

Cast: Jacob Tremblay, Julia Roberts, Owen Wilson

Genre: Drama

Story line: A 10 years-old boy born with a facial deformity is destined to fit in at a new school, and to make everyone understand he is just another ordinary kid, and that beauty is not skin deep.

Relation with genetics: Auggie suffers Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. This condition affects an estimated 1 in 50,000 people. In most cases, it is due to a genetic mutation of chromosome 5. Specifically, in the gene TCOF1, involved in the development of bones and other tissues of the face.

Video 1. Wonder trailer (Source: YouTube)

JULIA’S EYES (2010)

Director: Guillem Morales

Cast: Belén Rueda, Lluís Homar, Julia Gutiérrez Caba

Genre: Terror

Story line: It tells the story of a woman slowly going blind, the death of her twin sister tries to uncover the mysterious.

Relation with genetics: Both Julia and her sister suffer from retinitis pigmentosa. This disease causes the progressive loss of vision, affecting the retina, which is the layer of light-sensitive tissue in the back of the eye.

The first symptoms tend to be the loss of night vision and difficult to guide in low light. Later, the disease produces the appearance of blind spots in the lateral vision. With the passage of time, these blind spots come together producing a tunnel vision (Figure 1). Finally, this leads to blindness.

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Figure 1. Comparison between normal view and view wtih retinitis pigmentosa (Source: EyeHealthWeb)

The inheritance pattern can be autosomal dominant, recessive or linked to the X chromosome. In the first case, a single copy of the altered gene in each cell is sufficient to cause the disease. Most people with autosomal dominant retinitis pigmentosa have an affected father and other family members with the disorder.

Video 2. Julia’s eyes trailer (Source: YouTube)

MY SISTER’S KEEPER (2009)

Director: Nick Cassavetes

Cast: Cameron Díaz, Abigail Breslin, Alec Baldwin

Genre: Drama

Story line: Sara and Brian Fitzgerald’s life with their young son and their two-year-old daughter, Kate, is forever altered when they learn that Kate has leukaemia. The parents’ only hope is to conceive another child, Anna, specifically intended to save Kate’s life. Kate and Anna share a bond closer than most sisters: though Kate is older her life depends on Anna. Until Anna, now 11, says “no. Seeking medical emancipation, she hires her own lawyer, initiating a court case that divides the family and that could leave Kate’s rapidly failing body in the hands of fate.

Relation with genetics: Leukemias are the first type of cancer in which genetic alterations were described, such as translocations, which are the most frequent (more than 50% of cases). In addition, these have high prognosis and diagnostic value. There are many types of leukemias, therefore it is a diverse group of blood cancers, which affect blood cells and bone marrow. It is the most frequent type of cancer in children; however, it affects more adults than children.

A first classification is based on the lineage: lymphoid (blood-forming cells) or myeloid (cells of the bone marrow). At the same time, you are (lymphoid or myeloid) also classified according to the clinical presentation: acute (symptoms in short period of time and severe symptoms) or chronic (the time is longer).

In adults, acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) are more frequent, while in children it is acute lymphoblastic leukemia (ALL).

Video 3. My sister’s keeper trailer (Source: YouTube)

LORENZO’S OIL (1992)

Director: George Miller

Cast: Nick Nolte, Susan Sarandon, Peter Ustinov

Genre: Drama

Story line: The story concerns 5-years-old Lorenzo, suffering mightily from an apparently incurable and degenerative brain illness called ALD. His parents, an economist and a linguist, refuse to accept the received wisdom that there is no hope, and set about learning biochemistry to pursue a cure on their own. The film becomes an intriguing scientific mystery mixed with a story of pain, grief, and the strain on the two adults.

Relation with genetics: Lorenzo suffers from adrenoleukodystrophy (ADL) or also known as Schilder’s disease. It is a disease that mainly affects boys, since it has a pattern of inheritance linked to the X chromosome. It is in this chromosome where the ABCD1 gene is located, involved in the transport of very long chain fatty acids in peroxisomes (organelles involved in the metabolism of fatty acids).

It mainly affects the nervous system and the adrenal glands, which are small glands located in the upper part of each kidney. In this disorder, myelin deteriorates, the coating that isolates the nerves in the brain and spinal cord, reducing the ability of the nerves to transmit information to the brain. In addition, damage to the outer layer of the adrenal glands cause a shortage of certain hormones, resulting in weakness, weight loss, changes in the skin, vomiting and coma.

Video 4. Lorenzo’s oil trailer (Source: YouTube)

REFERENCES

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Metal hyperaccumulation in plants

During million years the evolution leaded plants to develop different strategies to defence from natural enemies, giving rise to an evolutionary weaponry war in which the survival of ones and others depends into the ability to beat the other’s adaptations. It is in that scenario where the high-level accumulation of heavy metals in plants plays an important role.

INTRODUCTION

Boyd (2012) commented that plant defences can be grouped in different categories:

  • mechanic: thorns, coverage, etc.
  • chemical: different organic and inorganic components.
  • visual: crypsis and mimicry .
  • behavioural: related with phenology’s modification.
  • and associative: symbiosis with other organisms, such is the case of the genus Cecropia, which has stablished a symbiotic relationship with ants of the genus Azteca, who protects these plants – to know more: Plants and animals can also live in marriage-.

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Mechanic defence with thorns (Author: Karyn Christner, Flickr, CC).

It is known that chemical defence is ubiquitous, and thus, a lot of interactions among organisms can be explained for this reason. In this sense, some plants contains high levels of certain chemical elements, frequently metals or metallic components, which plays an important role in the defence, these plants are the heavy metal hyperaccumulating plants.

Heavy metal hyperaccumulating plants and their main characteristics

This plants belong to several families, thus hyperaccumulation is an independent acquisition occurring different times during the evolution. In all cases, hyperaccumulation allowed the ability to grow soils with high levels of heavy metals and to accumulate extraordinary amounts of heavy metals in aerial organs. It is known that the concentration of these chemical elements in hyperaccumulating plants can be 100 – 1000 times higher than in non-hypperaccumulating plants.

Generally, chemistry describes heavy metal as transition metals with atomic mass higher than 20 and with a relative density around 5.  But, from a biological point of view, heavy metals or metalloids are elements which can be toxic in a low concentration. Even though, hyperaccumulating plants has become tolerant, i.e., they hypperacumulate this heavy metals without presenting phytotoxic effects (damage in plant tissues due toxicity).

In this sense, there are three main characteristics typically present in all hyperaccumulating plants:

  • Increased absorption rate of heavy metals.
  • Roots that perform translocation more quickly.
  • Great ability to detoxify and accumulate heavy metals in sheets.

Thus, hyperaccumulating plants are prepared to assimilate, translocate and accumulate high-levels of heavy metals in vacuoles or cellular wall. In part, it is due to the overexpression of genes codifying for membrane transporters.

The threshold values that allow to differentiate a hyperaccumulating plant from a non-hyperaccumulating one are related to the specific phytotoxicity of each heavy metal. According to this criterion, hyperaccumulating plants are plants that when grown on natural soils accumulate in the aerial parts (in grams of dry weight):

  • > 10 mg·g-1 (1%) of Mn or Zn,
  • > 1 mg·g-1 (0,1%) of As, Co, Cr, Cu, Ni, Pb, Sb, Se or Ti
  • or > 0,1 mg·g-1 (0,01%) of Cd.

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Minuartia verna, copper hyperacumulating plant (Autor: Candiru, Flickr, CC).

THE ORIGIN OF HYPERACCULATING PLANTS AND THEIR IMPLICATIONS

Till the moment, several hypothesis has been proposed to explain why certain plants can hyperaccumulate heavy metals:

  • Tolerance and presence of metals in soils.
  • Resistance to drought.
  • Interference with other neighbouring plants.
  • Defence against natural enemies.

The most supported hypothesis is “Elemental defence”, which indicates that certain heavy metals could have a defensive role against natural enemies, such as herbivores and pathogens. So, in the case these organisms consume plants, they should present toxic effects, which would lead them to die or at least to reduce the intake of this plant in future. Even though heavy metals can act through their toxicity, this does not guarantee plants will not be damaged or attacked before the natural enemy is affected by them. For this reason, it is still necessary a more effective defence which allow to avoid the attack.

In contrast, according to a more modern hypothesis, the “Joint effects”, heavy metals could act along with other defensive organic components giving rise to a higher global defence. The advantages of inorganic elements, including heavy metals, are that they are not synthetized by plants, they are absorbed directly from the soil and thus a lower energetic cost is invested in defence, and also they cannot be biodegraded. Even though, some natural enemies can even avoid heavy metal effects by performing the chelation, i.e., using chelators (substances capable of binding with heavy metals to reduce their toxicity) or accumulating them in organs where their activity would be reduced. This modern hypothesis would justify the simultaneous presence of several heavy metals and defensive organic components in the same plant, with the aim to get a higher defence able to affect distinct natural enemies, which would be expected to do not be able to tolerate different element toxicity.

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Thlaspi caerulescens, zinc hyperaccumulating plant (Autor: Randi Hausken, Flickr, CC).

On the other hand, it has been shown that certain herbivores have the ability to avoid the intake of plants with high levels of heavy metals, doing what is called “taste for metals“. Although this is known to occur, the exact mechanism of this alert and avoidance process is still uncertain.

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Solanum nigrum, cadmium hyperaccumulating plant (Autor: John Tann, Flickr, CC).

Additionaly, even tough heavy metal concentration in plant are really high, some herbivores manage to surpass this defense by being tolerant, i.e., their diet allows them to intake high dosis of metals and, thus, consume the plant. This could lead to think some herbivores could become specialist in the intake of hyperaccumulating plants, and, thus, this type of defence would be reduced to organisms with varied diets, which are called generalists. It has been demonstrated to not be true, as generalists herbivores sometimes present a higher preference and tolerance for hyperaccumulating plants than specialist organisms.

For all these reasons, it can be said that evolution is still playing an important role in this wonderful weaponry war.

Difusió-anglès

 REFERENCES

  • Boyd, R., Davis, M.A., Wall, M.A. & Balkwill K. (2002). Nickel defends the South African hyperaccumulator Senecio coronatus (Asteraceae) against Helix aspersa (Mollusca: Pulmonidae). Chemoecology 12, p. 91–97.
  • Boyd, R. (2007). The defense hypothesis of elemental hyperaccumulation: status, challenges and new directions. Plant soil 293, p. 153-176.
  • Boyd, R. (2012). Elemental Defenses of Plants by Metals. Nature Education Knowledge 3 (10), p. 57.
  • Laskowski, R. & Hopkin, S.P. (1996). Effect of Zn, Cu, Pb and Cd on Fitness in Snails (Helix aspersa). Ecotoxicology and environmentak safety 34, p. 59-69.
  • Marschner, P. (2012). Mineral Nutrition of Higher Plants (3). Chennai: Academic Press.
  • Noret, N., Meerts, P., Tolrà, R., Poschenrieder, C., Barceló, J. & Escarre, J. (2005). Palatability of Thlaspi caerulescens for snails: influence of zinc and glucosinolates. New Phytologist 165, p. 763-772.
  • Prasad, A.K.V.S.K. & Saradhi P.P. (1994).Effect of zinc on free radicals and proline in Brassica and Cajanus. Phytochemistry 39, p. 45-47.
  • Rascio, N. & Navari-Izzo, F. (2011). Heavy metal hyperaccumulating plants: How and why do they do it? And what makes them so interesting?. Plant Science 180 (2),p. 169-181.
  • Shiojiri, K., Takabayashi, J., Yano, S. & Takafuji, A. (2000) Herbivore-species-specific interactions between crucifer plants and parasitic wasps (Hymenoptera: Braconidae) that are mediated by infochemicals present in areas damaged by herbivores. Applied Entomology and Zoology 35, p. 519–524.
  • Solanki, R. & Dhankhar, R. (2011). Biochemical changes and adaptive strategies of plants under heavy metal stress. Biologia 66 (2), p. 195-204.
  • Verbruggen, N., Hermans, C. & Schat, H. (2009). Molecular mechanisms of metal hyperaccumulation in plants. New Phytologist 181 (4), p. 759–776.
  • Wenzel, W.W. & Jockwer F. (1999). Accumulation of heavy metals in plants grown on mineralised soils of the Austrian Alps. Environmental pollution 104, p. 145-155.

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.

WHY IS IT CALLED THAT?

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.

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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.

WHAT ARE THE FEATURES THAT CHARACTERIZE THEM?

  • 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

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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…

WHICH IS THE ROLE OF GENETICS?

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.

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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.

NONDISJUNCTION

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.

TRANSLOCATION

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.

MOSAICISM

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.

HAVING A CHILD WITH DOWN SYNDROME

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).

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

REFERENCES

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