Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel test streamlines testing for Huntington Disease

13.02.2013
High level of sensitivity and specificity reduces need for additional testing, reported in the Journal of Molecular Diagnostics

A new test may help to streamline genetic testing for Huntington Disease (HD) by generating accurate results, avoiding unnecessary additional testing, and improving turnaround time.

The test, which uses chimeric or triplet repeat primed PCR (TP PCR) methodology, yielded results that were 100% concordant with standard genotyping methods in an analysis of 246 samples. The high sensitivity and specificity of the test could reduce the number of false negative results and facilitate both diagnosis and prognosis by correctly sizing the genetic abnormality characteristic of HD.

Huntington disease (also known as Huntington's disease or Huntington's chorea) is an inherited and progressive neurodegenerative disorder that typically becomes apparent during a person's thirties or forties. With time, HD patients develop diminished muscle coordination that is evident in walking, speaking, and swallowing and undergo changes in personality and thinking ability. A mutation in the Huntingtin gene leads to an abnormal number of repeats of a sequence of three nucleotides known as CAG. Based on the number of CAG repeats, a person may be deemed to be normal (10-35 repeats), at low risk (36-39 repeats), or at high risk (greater than 40 repeats) of having or developing HD symptoms. That is why accurately determining the number of CAG repeats is so important.

In this study, 246 samples that had been previously analyzed by other methods were tested with the new method (TP PCR). The samples included 14 DNA reference samples from the Coriell Cell Repositories, three samples from the College of American Pathologists 2002 Survey, and 229 samples from individuals tested at ARUP Laboratories for clinical purposes by standard technologies, explained lead investigator Elaine Lyon, PhD, Medical Director of Molecular Genetics, ARUP Laboratories and its Institute for Clinical and Experimental Pathology, and Department of Pathology, University of Utah, Salt Lake City, UT. Normal samples were included as well as those with a wide range of CAG repeats. The samples were blinded and analyzed.

The results showed that TP PCR correctly sized 240 of the 246 samples. All of the 100 samples in the normal and low risk groups were correctly sized. In the 146 samples of those known to be affected by HD (those with > 39 CAG repeats), the results for 140 correctly matched that found with other methods whereas the number of CAG repeats differed by ±1 in 6 samples, a difference said by the authors to be within the precision of the method at higher repeat numbers. Up to 101 CAG repeats could be accurately sized with this test. Even samples that were found to be challenging to analyze with other methods could be assessed solely and accurately by TP PCR.

Another advantage of this new method is its ability to identify true homozygous normal samples, thus avoiding further testing. With other methodologies, if a sample appears homozygous for the normal allele, additional testing, often with Southern blot analysis, is still recommended because of the risk of false negatives. "Southern blotting is expensive, labor intensive, requires high concentrations of DNA, and can delay turnaround time," says Dr. Lyon. However, when HD is suspected in children, Dr. Lyon and colleagues recommend that even with TP PCR, apparently homozygous samples should undergo further testing.

TP PCR uses a forward and reverse chimeric primer to amplify from multiple priming sites within the trinucleotide repeat. TP PCR produces a characteristic ladder on a fluorescence electropherogram that allows the rapid and inexpensive identification and quantification of expanded repeats. Major peaks and minor peaks (stutters) representing CAG repeats can be analyzed and sized automatically using commercially available software.

David Sampson | EurekAlert!
Further information:
http://www.elsevier.com

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>