Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deletions and duplications in the exome can help pinpoint cause of unexplained genetic diseases

02.06.2014

Analysis of genetic variation in the exome, the DNA sequence of genes that are translated into protein, can aid in uncovering the cause of conditions for which no genetic cause could previously be found, and this can directly impact clinical management, the annual conference of the European Society of Human Genetics will hear today.

Dr Jayne Hehir-Kwa, Assistant Professor of Bioinformatics in the Translational Research group, Department of Human Genetics, Radboud UMC, Nijmegen, The Netherlands, will describe results from her group's study that set out to determine whether copy number variants (CNVs), large genomic deletions or duplications, can contribute to diseases other than intellectual disability.

The role of CNVs in intellectual disability is well known, but their implication in other conditions is less so. "There are, for example, case reports describing deletions in blindness, but no-one has determined the full extent of CNVs in other patient groups," Dr Hehir-Kwa will say.

The team screened 600 patients for which no diagnosis or causal mutation could be found using current whole exome sequencing (WES) methodology, and looked genome-wide for a causal deletion or duplication. It is, they say, the first time anyone has screened systematically for a disease mechanism in such a large and diverse patient group, including five heterogeneous conditions – intellectual disability, deafness, blindness, metabolic disorders, and movement disorders.

"For these patient groups, targeted gene approaches have been traditionally used for mutation screening and hence the contribution of CNVs to these disease groups has never been established and genome-wide testing rarely applied," says Dr Hehir-Kwa. "Our results show that CNVs are a relatively common, clinically-relevant event."

CNVs were found in patients with many different kinds of disorders, for example retinitis pigmentosa (blindness), Usher syndrome (deafness), Bethlem/Ulrich myopathy (a congenital form of muscular dystrophy), hypotonia-cystinuria syndrome (a neonatal-onset metabolic disorder) and X-linked immunodeficiency (an inherited disorder of the immune system).

"Although WES is not perfect in terms of completely cataloguing genomic variation, our work has shown that it can play an important part in diagnosis. In addition to helping us devise better clinical management strategies for patients, it also affects their prognosis and provides information which can aid us with reproductive counselling for affected individuals," says Dr Hehir-Kwa. "As a result, we are now offering the CNV screening performed in our study as a standard diagnostic procedure in exome analysis for patients where the genetic cause of their condition has not been found previously."

The diagnostic yield differs between the different disease categories, the researchers say. Traditional screening for genetic mutations can explain 27% of intellectual disability, 52% of blindness, and up to 20% of individuals with mitochondrial and movement disorders. "This means that between 48-80% of patients screened with WES are not given a genetic diagnosis. By looking for CNVs in the exon regions of these undiagnosed patients we estimate that we can find such a diagnosis in about a further four percent.

In particular, the blindness conditions seem to have the highest yield of CNVs – up to seven percent," says Dr Hehir-Kwa. "I would like to see screening for more types of genomic variants become standard procedure in genetic diagnostics. The genome of an individual can contain all kinds of different variants, in all shapes and sizes, and it is important that we take all these variations into account." WES, when offered as a first tier diagnostic test, can give a high diagnostic yield, and the result is faster diagnostics at lower cost.

"The more complete and thorough we can make such a diagnostic test, the more accessible we make genetic testing for the public. However, clinical health care professionals need to be well informed about the different genetic disease mechanisms to provide the best possible counselling for patients," Dr Hehir-Kwa will conclude.

Mary Rice | Eurek Alert!
Further information:
https://www.eshg.org/

Further reports about: CNVs Genetics Human blindness deafness diagnosis disability diseases disorder disorders duplications genomic metabolic variants

More articles from Life Sciences:

nachricht Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland

nachricht Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Data use draining your battery? Tiny device to speed up memory while also saving power

The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.

Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Data use draining your battery? Tiny device to speed up memory while also saving power

14.12.2018 | Power and Electrical Engineering

Tangled magnetic fields power cosmic particle accelerators

14.12.2018 | Physics and Astronomy

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>