Two studies published 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.
One was also made possible by some of the $7 billion that US
President Barack Obama directed to the National Institutes of
Health in September from the $7.1 trillion economic stimulus
package.
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.
Recessive genes
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
$US50,000," 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.
