Navigation Links
Trisomy 21: How an extra little chromosome throws the entire genome off balance
Date:4/17/2014

Occurring in about one per eight hundred births, Down syndrome - or trisomy 21 - is the most frequent genetic cause of intellectual disability. It results from a chromosomal abnormality where cells of affected individuals contain a third copy of chromosome 21 (1% of the human genome). A study conducted by Stylianos Antonarakis and his team in the Department of Genetic Medicine and Development at the University of Geneva (UNIGE) Faculty of Medicine, published in Nature, shed light on how the extra chromosome 21 upsets the equilibrium of the entire genome, causing a wide variety of pathologies.

Despite much research, the exact mechanisms causing the various symptoms associated with Down syndrome remain a mystery. According to a hypothesis called gene dosage disequilibrium, the presence of a third chromosome 21 could influence the expression of all the other genes in the genome. That is, this extra genetic material could disrupt the process through which information carried in the genes is decoded, therefore modifying the cellular function.

Based on this hypothesis, several research groups have tried, so far without success, to identify changes in gene expression within trisomic cells and link them with symptoms seen in patients. However, as the level of most gene expression varies from one person to another, it is extremely difficult to discriminate between changes exclusively linked to trisomy 21 and those due to natural variation between individuals.

Comparing Identical Twins

At UNIGE, Stylianos Antonarakis's team has the unique opportunity to examine the genomes of two identical twins with the exact same genetic makeup, except for an extra chromosome 21 present in one of them. Indeed, the chromosome 21 distribution error can take place during an early cellular division, after the original fertilized egg splits in two.

To compare gene expression levels between the twins, UNIGE researchers used recent, high-throughput sequencing technologies and other biotechnological tools developed within the Department of Genetic Medicine and Development, or in collaboration with scientists in Strasbourg, Barcelona, Amsterdam, and Seattle. They were thus able to eliminate interindividual variations and identify the changes in gene expression exclusively due to trisomy 21.

Small chromosome, big consequences

The researchers noticed that the expression of genes located on all the other chromosomes (outside of chromosome 21) were disturbed in trisomic cells. We were very surprised by this result, explains Audrey Letourneau, who co-authored this study. It does seem that this extra little chromosome has a huge influence on the entire genome.

Generally speaking, chromosomes are divided into domains that contain genes with rather similar levels of RNA production. RNA is the molecule which transmits the information contained in DNA, before this information is translated into proteins with precise functions. In the twin with Down syndrome, the domains are sometimes over-expressed, and sometimes under-expressed when compared with the healthy twin.

By comparing their results with data previously published by other research groups, UNIGE researchers noticed that this specific chromosomes organization correlates with DNA position in the cell nucleus. Therefore, domains over-expressed in the twin with Down syndrome correspond to portions of DNA known to primarily interact with the nucleus periphery.

This study therefore shows for the first time that the DNA position in the nucleus or the biochemical characteristics of DNA-proteins interactions in the trisomic cells is modified, leading to changes in the gene expression profile. Federico Santoni, who co-authored this study, notes that, These changes do not only affect chromosome 21, but the entire genome. The presence of about 1% of extra genetic material in the trisomic cells hence modifies the function of the whole genome, and disrupts the general equilibrium of gene expression. We could make an analogy with climate change, adds Professor Antonarakis. Even if the temperature rises by only one or two degrees, it will rain a lot less in the tropics, and a lot more in temperate zones. Global climate equilibrium can thus be disrupted by a tiny element.

This study opens the door to a new way of understanding the molecular mechanisms that explain the symptoms of Down syndrome. The UNIGE team will now continue its research to understand molecular mechanisms at stake, and link this disrupted gene expression with the phenotypes associated with Down syndrome. The end goal of this research is to find ways to revert the dysregulation of cellular gene expression back to normal, with the objective to correct the cellular abnormalities in this disease. Progress in this field could also be applied to other diseases with genome imbalance.


'/>"/>

Contact: Stylianos Antonarakis
stylianos.antonarakis@unige.ch
41-223-795-708
Universit de Genve
Source:Eurekalert  

Related biology news :

1. Complex genetic architectures: Some common symptoms of trisomy 21
2. Plant extract offers hope for infant motor neuron therapy
3. Garcinia Cambogia Extract Review Company Garcinia Ex Announces the Launch of its Updated Website
4. A magnetic nanoparticles-based method for DNA extraction from the saliva after stroke
5. Wayne State cholesterol study shows algal extracts may counter effects of high fat diets
6. A universal RNA extraction protocol for land plants
7. Tailored methane measurement services are to be developed for shale gas extraction, municipal waste
8. Study investigates extraordinary trout with tolerance to heavily polluted water
9. Herbal extract boosts fruit fly lifespan by nearly 25 percent, UCI study finds
10. Quit smoking? Vitamin E may give extra boost to heart health
11. Scientists decode genome of painted turtle, revealing clues to extraordinary adaptations
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Trisomy 21: How an extra little  chromosome throws the  entire genome off balance
(Date:6/1/2016)... NEW YORK , June 1, 2016 ... Biometric Technology in Election Administration and Criminal Identification to ... According to a recently released TechSci Research report, " ... Sector, By Region, Competition Forecast and Opportunities, 2011 - ... $ 24.8 billion by 2021, on account of growing ...
(Date:5/16/2016)... , May 16, 2016   EyeLock LLC ... today announced the opening of an IoT Center of ... strengthen and expand the development of embedded iris biometric ... unprecedented level of convenience and security with unmatched biometric ... one,s identity aside from DNA. EyeLock,s platform uses video ...
(Date:5/3/2016)... 2016  Neurotechnology, a provider of high-precision biometric ... Biometric Identification System (ABIS) , a complete system ... ABIS can process multiple complex biometric transactions with ... fingerprint, face or iris biometrics. It leverages the ... MegaMatcher Accelerator , which have been used ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... June, 23, 2016  The Biodesign Challenge (BDC), a ... ways to harness living systems and biotechnology, announced its ... in New York City . ... students, showcased projects at MoMA,s Celeste Bartos Theater during ... , MoMA,s senior curator of architecture and design, and ...
(Date:6/23/2016)... ... ... STACS DNA Inc., the sample tracking software company, today announced that Dr. Hays ... DNA as a Field Application Specialist. , “I am thrilled that Dr. Young ... DNA. “In further expanding our capacity as a scientific integrator, Hays brings a wealth ...
(Date:6/23/2016)... , June 23, 2016  Blueprint Bio, a ... discoveries to the medical community, has closed its Series ... Matthew Nunez . "We have received a ... the capital we need to meet our current goals," ... provide us the runway to complete validation on the ...
Breaking Biology Technology: