Mitochondria are key suppliers of the energy needed for the multiple functions of our cells.

A team led by CHOP’s Marni J. Falk, MD, has expanded next-generation gene tools designed to sequence nuclear DNA to analyze a separate source of DNA — that found within mitochondria. Mitochondria are key suppliers of the energy needed for the multiple functions of our cells. Mitochondria contain their own DNA, and play a pivotal role in human health and disease.

“A first step in developing treatments for a disease is to understand its precise cause,” said Dr. Falk, director of the Mitochondrial-Genetic Disease Clinic. “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.”

In addition to her role at CHOP, Dr. Falk is also chair of the United Mitochondrial Disease Foundation’s Scientific and Medical Advisory Board.

To create their test— which they call the “1:1000 Mito-Plus Whole-Exome” kit — the researchers adapted an existing sequencing kit from Agilent Technologies, expanding it to encompass the mitochondrial genome.

While individual mitochondrial diseases are very rare, hundreds of causes of mitochondrial diseases are known. Some originate in mutations in DNA specific to the mitochondria, while many other mitochondrial diseases are based in nuclear DNA genes that affect mitochondrial function. The role of mitochondria in human disease has only been recognized since the 1980s, and is based on the pioneering research by CHOP’s own Douglas C. Wallace, PhD. However, many mitochondrial diseases remain poorly understood.

One complicating factor is heteroplasmy — a 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, Dr. Falk’s kit has the sensitivity to detect mitochondrial genome mutations present at levels as low as 8 percent.

The availability of the new test could help to shorten the “diagnostic odyssey” experienced by patients and families seeking the cause of debilitating and puzzling symptoms, said Dr. Falk. “Many families travel from one specialist to another for years, searching for the cause of their rare disease,” she said.

Specific treatments are not always available, but identifying their disease cause may be the first step toward discovering treatments, Dr. Falk noted.

To learn more about Dr. Falk’s research, see the full press release.