Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fishing for microdeletions that predispose an embryo to develop cancer syndromes in later life

11.03.2009
Researchers have used a common laboratory technique for the first time to detect genetic changes in embryos that could predispose the resulting children to develop certain cancer syndromes.

Current preimplantation genetic diagnosis techniques can detect mutations in very small bits of genes or DNA, but, until now, it wasn't easy to detect deletions involving whole genes or long sections of DNA in embryos.

The study, published online today (Wednesday 11 March) in Europe's leading reproductive medicine journal Human Reproduction [1], uses a technique called fluorescent in situ hybridization (FISH) to detect losses of small parts of whole chromosomes (microdeletions) in a single cell from an embryo. The work opens the way to test for microdeletions in patients with other genetic conditions as well as the two cancer predisposition syndromes treated in this study. [2]

Professor Joris Vermeesch, coordinator of the Genomics Core and head of Constitutional Cytogenetics, and Evelyne Vanneste, a PhD student, both at the Center for Human Genetics, University Hospital Leuven (Belgium), and their colleagues used FISH to carry out PGD in embryos from three couples where the women carried microdeletions for either neurofibromatosis type 1 (NF1) or Von Hippel-Lindau disease (VHL). As a result, the woman with the VHL mutation gave birth to healthy twins from embryos selected using FISH PGD.

Neurofibromatosis type 1 (also known as Von Recklinghausen disease) is a common inherited condition with an incidence at birth of one in 3,000-3,500. NF1 patients develop tumours of the nervous system, pigmented patches of skin and can have lower IQs. In 95% of people with NF1, a mutation is found in the NF1 gene, which is a tumour suppressor gene; but five per cent of NF1 patients have microdeletions of the gene, and large microdeletions can result in more severe symptoms.

Von Hippel-Lindau (VHL) disease is a rarer cancer syndrome, occurring in about one in 36,000 births. Symptoms of the disease include benign tumours of the central nervous system and benign and malignant tumours of organs such as the kidneys, adrenal glands and pancreas. It is an inherited condition caused by a mutation in the VHL tumour suppressor gene.

The strands of DNA that twist together to form the double helix structure are made up of lots of small sections called nucleotides. The nucleotides are made up of the four DNA bases – adenine, thymine, guanine and cytosine (or A,T,C,G). Mutations that can be detected by the conventional PCR (polymerase chain reaction) technique used in PGD are usually mutations of a single nucleotide or base. A deletion or microdeletion normally involves the loss of larger numbers of nucleotides.

Prof Vermeesch explained: "Current techniques using PCR to detect abnormalities in embryos can detect one base, nucleotide or letter change in the DNA, but they cannot be used when a person has a loss of the whole gene or a lot of letters – a microdeletion. Patients with these cancer predisposition syndromes, and some other conditions, usually carry only a single microdeletion. Now, for the first time, we have used FISH to detect these microdeletions in the embryo and thus can help carriers to create offspring without those anomalies.

"Importantly, microdeletions are not so rare in neurofibromatosis type 1. It is also becoming clear that genomic disorders caused by microdeletions, duplications and copy number variations are much more frequent than previously thought. The techniques we have used in this study will help a wide range of microdeletion carriers."

For each of the three women, the researchers created probes that could be used to identify NF1 or VHL deletions in the embryos. The embryos were obtained from the women using normal assisted reproduction techniques. They took two cells from each embryo and performed FISH to probe them for the microdeletions. Only embryos that FISH had identified as being healthy, without any microdeletions, were transferred to the women's wombs.

Ms Vanneste explained that although they had to make FISH probes specific to each woman, the NF1 microdeletions found tended to recur. "Therefore, most NF1 patients with a deletion carry the same deletion and our FISH PGD conditions can be rapidly replicated and re-used in other deletion carriers. It seems likely that the number of families that can benefit from FISH PGD will increase in years to come and we are continuing to help more families using this approach. However, for each condition a new probe has to be made. This is time-consuming, but we are currently developing tools to identify all similar genetic imbalances with a single technology."

[1] Preimplantation genetic diagnosis using fluorescent in situ hybridization for cancer predisposition syndromes caused by microdeletions. Human Reproduction. doi:10.1093/humrep/dep034

[2] PGD can be carried out already to detect a genetic susceptibility for some cancers, but only if the specific mutation is know (e.g. to detect the BRCA1/2 mutations that can lead to breast cancer developing). The majority of these cases involve a change in a single nucleotide, not a microdeletion.

Emma Mason | EurekAlert!
Further information:
http://www.eshre.com

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>