CARLSBAD, CA – In a scientific coup that could mean leaps for personalized medicine, two Baylor College of Medicine scientists have sequenced an individual's genome and identified the specific causative mutation associated with Charcot-Marie-Tooth Disease (CMT).

The disease is one of the most common inherited neurological disorders currently affecting 1 in 2,500 individuals in the United States. The scientists used genomic analysis technologies from Life Technologies Corp.

In a paper published today by The New England Journal of Medicine, geneticists Richard Gibbs and James R. Lupski, MD, asserted they used whole genome sequencing for the first time to identify the cause of an inherited disease.

Gibbs and Lupski worked together at Baylor's Human Genome Sequencing Center (HGSC), and used the Applied Biosystems SOLiD System, an ultra high throughput next-generation genomic analysis platform, to find the mutation implicated in CMT.

Lupski, who has been affected by the motor and sensory nerve function disorder since his early childhood, identified the genetic variant within his genome. Lupski, who comes from a family of 10 where he and three of his eight siblings have been affected by CMT, has been searching for the genetic mutation causing his disease for more than 20 years.

The discovery of the mutation is being hailed as groundbreaking because it demonstrates the power of DNA sequencing to pinpoint the cause of genetic disease and ultimately lead to the development of new therapies.

CMT primarily affects the human body's peripheral nerves, which exist outside the brain and spinal cord and supply the muscles and sensory organs in the limbs. Individuals with CMT may have weak lower leg and foot muscles, which may affect stride or result in foot deformities. It is not uncommon for muscle weakness to also occur in the hands, resulting in difficulty with fine motor skills. The severity of CMT varies in different individuals and even among family members with the disease.

Technology assist

Gibbs and Lupski used the SOLiD System to generate comprehensive sequence data of Lupski's entire personal genome, enabling the scientists to identify the key DNA mutations connected to Lupski's type of CMT. The platform's ability to achieve the life science industry's highest accuracy at a minimum depth of genome coverage demonstrates proof-of-principle for whole genome sequencing as a medical diagnostic for human disease. Based on the success of this research collaboration between Life Technologies and the HGSC, scientists at Baylor will now begin to apply this methodology to the discovery of rare genetic variants in the other 12,000+ genetic diseases.

"I've dedicated most of my career to understanding the genetic basis of CMT for very personal reasons," said Lupski. "By having a better understanding of this disease, my hope is that we – the healthcare industry and individuals affected by CMT – will be able to better mitigate its consequences."

"Translational research studies uncovering novel genetic information are maximized through collaborative efforts between industry and the research community," said Gibbs, director of Human Genome Sequencing at Baylor College of Medicine. "I believe the CMT research enabled through our relationship with Life Technologies represents the best demonstration of disease-related data to date."

"The elucidation of this genetic mutation using high-throughput sequencing is a powerful statement about the use of advanced genome analysis technologies as a discovery and diagnostic research tool and will help accelerate the promise of personalized medicine," said Shaf Yousaf, president of Genomic Analysis for Life Technologies. "There is tremendous opportunity to apply this research as proof-of-principle and rapidly advance the discovery of other rare genetic variants associated with disease."