Published March 11, 2010
Two studies published on Wednesday show it is possible to sequence the entire gene maps of families with inherited diseases and pinpoint the offending bit of DNA.
The studies, which would not have been possible a year or two ago, are the first real delivery of the promised transformation of medical science from the Human Genome Project's mapping of the human genetic code.
And in that study, the genetic researcher was himself one of the patients.
Dr. James Lupski of the Baylor College of Medicine in Houston has a recessive genetic disease called Charcot-Marie-Tooth syndrome. It affects the nerves stretching from the spinal cord to the arms, legs and feet.
Lupski has been experimenting on himself and his own family for years.
"We tried every other method for 25 years to find out which mutation was important," he said in a telephone interview.
"With this methodology we were able to do it. This is the first time whole genome sequencing has applied to actually find the cause of a disease."
Lupski had been taking blood samples from his grandparents, parents and siblings for years. He got close but the research was considered too risky for funding by the National Institutes of Health.
"He was only able to complete this study because of the stimulus money that we got," said Dr. Story Landis, director of the National Institute of Neurological Disorders and Stroke.
Her institute designated Lupski's project for about half a million dollars of the money that Obama directed to the NIH.
Lupski's team used a gene sequencer from Carlsbad, California-based Life Technologies to read the entire DNA code in the samples from Lupski and three of his siblings who have the syndrome, his parents and four other siblings who do not.
"It is a recessive disease and neither of my parents have the disease. Each of us who has it got one mutant allele (gene) from my mom and one mutant allele from my dad," he said.
Researchers know about 40 different genes that can cause Charcot-Marie-Tooth. But in each family, only one of these genes is involved.
The sequencing revealed a gene called SH3TC2, the researchers reported in the New England Journal of Medicine. Other groups are already working on a drug that may affect that gene, Lupski said.
The researchers also found that family members who inherited just one faulty copy of the gene had a predisposition to carpal tunnel syndrome, in which a nerve in the wrist can get pinched.
As prices are coming down on the cost of sequencing a human genome, more such research will be possible.
"We estimate that the entire effort would currently cost less than $50,000," the researchers wrote.
In a second study, Jared Roach of the Institute for Systems Biology in Seattle and colleagues sequenced the entire genomes of a family of four affected by two recessive genetic diseases — Miller syndrome, which can cause facial disfigurement, and primary ciliary dyskinesia, a lung disorder that raises the risk of respiratory infections because the hairlike extension on cells called cilia fail to move properly.
"Our results demonstrate the unique value of complete genome sequencing in families," they wrote in the journal Science.
They used a sequencer made by another one of the companies exploiting genomic sequencing, Complete Genomics based in Mountain View, California.