Featured Research

from universities, journals, and other organizations

Novel test streamlines testing for Huntington Disease

Date:
February 13, 2013
Source:
Elsevier Health Sciences
Summary:
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.

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by Elsevier Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mohamed Jama, Alison Millson, Christine E. Miller, Elaine Lyon. Triplet Repeat Primed PCR Simplifies Testing for Huntington Disease. The Journal of Molecular Diagnostics, 2013; DOI: 10.1016/j.jmoldx.2012.09.005

Cite This Page:

Elsevier Health Sciences. "Novel test streamlines testing for Huntington Disease." ScienceDaily. ScienceDaily, 13 February 2013. <www.sciencedaily.com/releases/2013/02/130213082445.htm>.
Elsevier Health Sciences. (2013, February 13). Novel test streamlines testing for Huntington Disease. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2013/02/130213082445.htm
Elsevier Health Sciences. "Novel test streamlines testing for Huntington Disease." ScienceDaily. www.sciencedaily.com/releases/2013/02/130213082445.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins