Collaboration rapidly connects fly gene discovery to human disease
A collaborative study by scientists at Baylor College of Medicine (BCM) and the Montreal Neurological Institute of McGill University, and published March 20 in the online, open access journal PLoS Biology, has discovered that mutations in the same gene that encodes part of the vital machinery of the mitochondrion can cause neurodegenerative disorders in both fruit flies and humans.
Vafa Bayat in Dr. Hugo Bellen's lab at BCM, examined a series of mutant fruit flies for defects leading to progressive degeneration of photoreceptors in the eye. They identified mutations in the fruit fly gene that encodes a mitochondrial enzyme known as the mitochondrial methionyl-tRNA synthetase (Aats-met). These mutations also shortened life span and caused other problems, including reduced cell proliferation.
Mitochondria are the power plants of the cell, and have their own mechanism for producing proteins, separate from the main cellular protein-producing machinery. Defects in genes that encode mitochondrial proteins have been previously associated with human metabolic and neurological disorders.
Dr. Bayat, a recent graduate from the Program in Developmental Biology at BCM, searched the medical literature for genetic neurological disorders that were thought to be caused by defects in the region of our genome that contains the human version of the Aats-met gene, MARS2. One such disease, Autosomal Recessive Spastic Ataxia with frequent Leukoencephalopathy (ARSAL), had already been mapped to this region of the genome by Dr. Bernard Brais and his colleagues, but the precise gene responsible was not known. Ataxias such as ARSAL are progressive neurodegenerative diseases that cause coordination problems, leading to modified gait and speech as well as other problems.
Dr. Isabelle Thiffault from the Montreal team identified complex rearrangements of the genetic material in the MARS2 gene of ARSAL patients. These unusual rearrangements resulted in reduced levels of the MARS2 enzyme, reduced synthesis of proteins by the mitochondria, and impaired mitochondrial function. As with the fruit fly mutants, the patients' cells also had increased levels of reactive oxygen species, which can damage cells and their genetic material, and slow cell proliferation.
"We found the same defect in the mitochondrial respiratory chains in the human cells, which produced a lot of reactive oxygen species," said Dr. Bayat. "When we feed the fly larvae antioxidants, they suppress the degenerative phenotypes in flies." The ability of antioxidants to counteract the negative consequences of the mutant gene in flies raises the possibility that a related approach might have beneficial effects in human patients, though this remains to be determined.
"While the discovery of mutations in fly genes has been linked to human disease before, it has often taken many years to decades to accomplish this," said Dr. Bellen. "This was a relatively quick process. In summary, we have shown that you can use flies to identify fly mutants with neurodegenerative phenotypes and that these mutants can assist in the identification of human disease genes."
More information: Bayat V, Thiffault I, Jaiswal M, Tétreault M, Donti T, et al. (2012) Mutations in the Mitochondrial Methionyl-tRNA Synthetase Cause a Neurodegenerative Phenotype in Flies and a Recessive Ataxia (ARSAL) in Humans. PLoS Biol 10(3): e1001288. doi:10.1371/journal.pbio.1001288
Provided by Public Library of Science
- Nna proteins play role in catastrophic neuron death in mice, flies -- and perhaps people Jun 24, 2010 | not rated yet | 0
- Cell's 'battery' found to play central role in neurodegenerative disease Jan 17, 2012 | not rated yet | 0
- Genetic map reveals clues to degenerative diseases Aug 24, 2011 | not rated yet | 0
- 'Drunk' fruit flies could shed light on genetic basis of human alcohol abuse Oct 20, 2006 | not rated yet | 0
- A fly lamin gene is both like and unlike human genes Jun 13, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | not rated yet | 0 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The use of genome-wide analysis (GWA), where the entirety of an individual's DNA is examined to look for the genomic mutations or variants which can cause health problems is a massively useful technology for diagnosing disease. ...
Genetics May 16, 2013 | not rated yet | 0
DNA databases might help identify victims of crime and human trafficking, but how do we safeguard the personal privacy of innocent victims and family members? A new report online May 15 in the Cell Press journal Trends in ...
Genetics May 15, 2013 | not rated yet | 0
An increasing number of U.S. children are experiencing gastrointestinal issues that require interventions to resolve, according to research presented at Digestive Disease Week (DDW).
12 hours ago | not rated yet | 0 |
The latest makeover to a massive psychiatric tome honored by some, reviled by others and even called the "Bible" of mental disorders is being released Saturday with a host of new changes.
10 hours ago | not rated yet | 0
A new case of the deadly coronavirus has been detected in Saudi Arabia where 15 people have already died after contracting it, the health ministry announced on Saturday on its Internet website.
10 hours ago | not rated yet | 0
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
20 hours ago | 5 / 5 (1) | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
21 hours ago | 5 / 5 (1) | 0 |
A ground-breaking advance in colonoscopy technology signals the future of colorectal care, according to research presented today at Digestive Disease Week(DDW). Additional research focuses on optimizing the minimal withdrawal ...
12 hours ago | 5 / 5 (2) | 0