Navigation Links
Scientists create 1-step gene test for mitochondrial diseases
Date:1/29/2013

More powerful gene-sequencing tools have increasingly been uncovering disease secrets in DNA within the cell nucleus. Now a research team is expanding those rapid next-generation sequencing tests to analyze a separate source of DNAwithin the genes inside mitochondria, cellular power plants that, when abnormal, contribute to complex, multisystem diseases.

The study team, headed by a specialist in mitochondrial medicine at The Children's Hospital of Philadelphia (CHOP), adapted next-generation sequencing to simultaneously analyze the whole exome (all the protein-coding DNA) of nuclear genes and the mitochondrial genome. "A first step in developing treatments for a disease is to understand its precise cause," said Marni J. Falk, M.D., the director and attending physician in the Mitochondrial-Genetic Disease Clinic at Children's Hospital. "We have developed a one-step, off-the-shelf tool that analyzes both nuclear and mitochondrial DNA to help evaluate the genetic cause of suspected mitochondrial disease."

Falk and colleagues describe their customized, comprehensive test, which they call the "1:1000 Mito-Plus Whole-Exome" kit, in the journal Discovery Medicine, published Dec. 26, 2012. Her co-corresponding author, biostatistician Xiaowu Gai, Ph.D., now of the Loyola University Stritch School of Medicine, collaborated on developing the test while at Children's Hospital.

While each mitochondrial disease is very rare in the population, hundreds of causes of mitochondrial diseases are known. Some originate in mutations in DNA specific to the mitochondria, tiny structures located outside the cell nucleus, while many other mitochondrial diseases are based in nuclear DNA genes that affect mitochondrial function. The role of mitochondria in human disease has been recognized only since the 1980s, based on pioneering research by Douglas C. Wallace, Ph.D., now at Children's Hospital, and a co-author of the current study.

Many mitochondrial diseases remain poorly understood. One complicating factor is heteroplasmya mixture of mutated and normal mitochondrial genomes within the same cells or tissues. In contrast to conventional gene sequencing, which can detect only heteroplasmic mutations that reach levels of at least 30 to 50 percent, the customized kit has the sensitivity to detect mitochondrial genome mutations present at levels as low as 8 percent. To achieve their results, the study team adapted an existing whole-exome sequencing kit from Agilent Technologies, expanding it to encompass the mitochondrial genome.

The availability of the new kit, said Falk, if used for either clinical or research purposes, may shorten the "diagnostic odyssey" experienced by many patients and families seeking the cause of debilitating and puzzling symptoms. "Many families travel from one specialist to another for years, searching for the cause of their rare disease," she says. Specific treatments are not always available, but identifying their disease cause may be the first step toward discovering treatments.

A second recent study by Falk and colleagues reviews progress in diagnosing mitochondrial disease, through their experience at a single center over a rapidly changing three-year period before whole-exome sequencing was generally available. The retrospective review in Neurotherapeutics, published Dec. 27, 2012, covers 152 child and adult patients evaluated at CHOP's Mitochondrial-Genetics Diagnostic Clinic from 2008 to 2011.

"Before 2005, very few individuals could receive definitive molecular diagnoses for mitochondrial diseases, because of limitations in both knowledge and technology," said Falk. "Since that time, the clinical ability to sequence whole mitochondrial DNA genomes has significantly improved the diagnosis of many mitochondrial disorders."

During the study period covered in the review article, the clinic at CHOP confirmed definite mitochondrial disease in 16 percent of patients and excluded primary mitochondrial disease in 9 percent. While many diagnostic challenges clearly remain, Falk says the advent of massively parallel nuclear exome sequencing is revealing increasingly more of the genes in nuclear DNA that affect mitochondrial function, and the precise genetic disorder in a given patient, even if it is novel or uncommon. She added that molecular genetics is yielding a more nuanced understanding of the cellular pathways underlying symptoms in many mitochondrial disorders. "Those pathways offer potential new targets for treating these disorders," said Falk.


'/>"/>

Contact: Dana Mortensen
Mortensen@email.chop.edu
267-426-6092
Children's Hospital of Philadelphia
Source:Eurekalert

Related medicine news :

1. Scientists Complete 1st Map of Emotional Intelligence in the Brain
2. Singapore scientists led by A*STARs GIS identify 4 mechanisms that contribute to gastric cancers
3. National Cancer Centre Singapore scientists discover p53 mutation hinders cancer treatment response
4. HIV-Like Virus Arose in Primates Millions of Years Ago, Scientists Say
5. Scientists Link More Genes to Common Brain Tumor
6. Temple scientists find cancer-causing virus in the brain, potential connection to epilepsy
7. Scientists identify new strategy to fight deadly infection in cystic fibrosis
8. Social Scientists call for more effective teaching in Higher Education
9. UT MD Anderson scientists find protein that reins in runaway network
10. Study Finds Older Male Scientists Likelier to Commit Research Fraud
11. NIH scientists identify protective role for antibodies in Ebola vaccine study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/22/2017)... ... February 22, 2017 , ... The Waismann Method® is providing a ... have recently fallen victim to America’s opioid epidemic. Now, opiate dependent individuals can be ... are free from the shame, stigma, and harmful labeling believed to prevent ...
(Date:2/22/2017)... ... February 22, 2017 , ... Giving patients with ... the emergency room, fewer hospital admissions, and better blood pressure and glycemic control, ... finds. The study can be found here . , The study comes ...
(Date:2/22/2017)... Angeles, CA (PRWEB) , ... February 22, 2017 , ... ... the recent addition of esteemed ophthalmologist, Dr. Steven H. Rauchman, practicing at North ... common in auto accidents, product liability, premise liability and other personal injury cases. ...
(Date:2/22/2017)... ... 22, 2017 , ... The first-ever National Heart Valve Disease ... individuals join together to increase recognition about the risks of heart valve disease ... we mark a nationwide movement to raise awareness about a disease that has ...
(Date:2/22/2017)... ... 2017 , ... Bellus Medical, a leader in medical aesthetics, ... of Platelet Rich Plasma (PRP). PRP systems are used by physicians in areas ... and provide a faster and more efficient healing process. There are many systems ...
Breaking Medicine News(10 mins):
(Date:2/22/2017)... and PUNE, India , February 22, 2017 ... was valued at $3,453 million in 2015 and is projected to reach $5,334 million ... implants segment held nearly two-fifths of the total market in 2015. ... ... ...
(Date:2/22/2017)... , Feb. 22, 2017  Known for selling ... cabinets, the widow of prominent California ... should know something else about the British conglomerate that ... immorally by attempting to steal her late husband,s invention, ... and operated by Dr. Gilbert until his violent death ...
(Date:2/22/2017)... A research report by Arcview Market Research focused on cannabis ... changing landscape of the legal market reveals that regulated cannabis sales ... , a 30% increase from 2015. According to the research ... 2021 representing a 26 percent compound annual growth rate. The use ... Canada is gradually becoming more mainstream thanks ...
Breaking Medicine Technology: