Family DNA Maps May Speed Disease-Gene Discoveries, Doctors Say
March 11, 2010, 6:28 AM ESTBy Jason Gale and Rob Waters
March 11 (Bloomberg) -- Fewer genetic mutations are inherited than scientists previously thought, according to two family-based studies that promise to speed the discovery of so- called disease genes.
Two U.S. research teams conducted independent, genome-wide studies to pinpoint the mutations responsible for three rare diseases. The approach, detailed yesterday in the New England Journal of Medicine and Science, is being used to find genes that may mitigate inherited disorders and offer hope for people with conditions such as Huntington’s disease.
Comparing the genetic blueprint of parents and their children can narrow the hunt for disease-causing genes to a handful of candidates rather than the thousands that are identified when a genome is analyzed in isolation, said Leroy Hood, a researcher who helped sequence the first family genome at Seattle’s Institute for Systems Biology. San Diego-based Illumina Inc. can sequence a human genome for less than $10,000.
“There will be an explosion of family sequencing that will identify disease genes,” Hood, 71, said in a telephone interview yesterday. “My prediction is that in 10 years or so, most of us will have our genome sequences done as part of our medical records and it will be an important part of predictive medicine.”
Writing in the journal Science yesterday, Hood and colleagues showed how parents with no genetic abnormalities carried recessive genes that resulted in their son and daughter being born with two rare conditions: Miller’s syndrome and primary ciliary dyskinesia.
60 Mutations
By comparing the DNA sequences of all four family members, the authors found that the parents gave 30 mutations each, for a total of 60, to their children, the researchers. Earlier studies had estimated that parents pass 75 gene mutations each to their children, with many of those changes not having any consequence.
“The mutation rate was less than half of what we’d thought,” said co-author Lynn Jorde, professor and chairman of human genetics at the University of Utah, in a statement.
The number of gene mutations each parent passes to their child probably varies depending on how old the parents are, particularly the father, said Chad Huff, a researcher in Jorde’s lab.
Hood and colleagues are now sequencing 100 genomes from U.S. families that have Huntington’s, an incurable, degenerative neurological condition that’s passed from parent to child through a mutation. The scientists are looking for a gene that may modify, delay or change the course of the disease. Analysis of the data will begin in a few months, he said.
‘Simple Protein’
“Suppose this modifier gene made a simple protein that was secreted into the blood and that was what delayed the disease, then you could manufacture that protein and give it to people with Huntington’s disease,” Hood said. “That’s the kind of idea that you could think about.”
The Human Genome Project, completed in 2003, cost about $3 billion, according to the University of Utah School of Medicine.
Plummeting costs mean DNA sequencing will soon become routine in medical diagnoses, shedding light on the genetic characteristics of inheritable diseases, Richard P. Lifton, chairman of the genetics department at Yale University School of Medicine in New Haven, Connecticut, wrote in an editorial in the New England Journal of Medicine yesterday.
Nerve Disorder
In the same journal, Richard A. Gibbs, professor of molecular and human genetics at Baylor College of Medicine in Houston, reported single-gene mutations responsible for an inherited nerve disorder known as Charcot-Marie-Tooth disease afflicting his colleague, James R. Lupski, and three of Lupksi’s seven siblings.
The authors studied 10 Lupski family members to understand the genetic cause of the disease, previously linked with dozens of errant genes.
“This is just one of a series of events that indicates a revolution in the way that we are doing genetics,” said George M. Church, professor of genetics at Harvard Medical School, in a telephone interview. “It’s signaling the early arrival of inexpensive DNA sequencing.”
Eric Topol, professor of translational genomics at the Scripps Research Institute in San Diego, plans to publish his own family genome study within a few months, and will focus future research on low-frequency insertions and deletions responsible for human-genome structural variance. He said he expects “an accelerated pace of discovery.”
“Until now, it was overestimated how many mutations occur from one generation to the next,” Topol said in a telephone interview. “It’s nice to know that it’s really de minimis. These mutations can be good or bad, but perhaps more likely to be bad.”
--Editors: Kristen Hallam, Angela Cullen
To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net; Rob Waters in San Francisco at rwaters5@bloomberg.net.
To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net.
