For first time, Seattle team cracks genome of entire family
The people who have had their genetic blueprints fully deciphered wouldn't fill a typical coffee shop. Now, Seattle scientists have ushered a family of four into that elite group.
Seattle Times science reporter
Miller syndromeWhat is it? An extremely rare syndrome caused by a recessive gene passed along by parents.
Characteristics: Underdeveloped cheekbones, abnormally small jaw, cleft palate, cup-shaped ears, drooping of the lower eyelids. Patients also can have incomplete limb development, webbing of fingers or toes, absence of certain fingers and/or toes. It does not affect intelligence.
Treatment: Surgeries may be necessary depending on the severity.
Source: The National Craniofacial Association
The people who have had their genetic blueprints fully deciphered wouldn't fill a typical coffee shop.
Now, Seattle scientists have ushered a family of four into that elite group.
It's the first time researchers have sequenced the entire genetic makeup — called a genome — for all members of a family, said project leader David Galas of the Institute for Systems Biology (ISB), a nonprofit research center in Seattle's Fremont neighborhood.
Comparing genomes between the parents and their offspring allowed the researchers to quickly identify the gene responsible for Miller syndrome, an extremely rare disorder that afflicts both of the children.
It's an approach Galas predicts will be widely used in the future to help ferret out the genetic roots of diseases as complex as Alzheimer's and diabetes.
"Looking at families will give a real boost to our power to identify ... the various genetic contributions to disease," he said. "My guess is this will just explode in the next two to three years."
The research, published online Wednesday by the journal Science, also foreshadows another impending explosion: the soon-to-be-routine use of genome sequencing in research and medicine.
"A couple of years ago, we wouldn't have imagined being able to do this," said Dr. Richard Lifton, of Yale University School of Medicine, who was not involved in the project.
It took 13 years and an investment of nearly $1 billion to sequence the first human genome in the early 2000s. When the Seattle team launched its analysis in 2009, the cost had plummeted to $20,000 per genome. The lab work took a month.
Today, the price is approaching $10,000. Lifton predicts $250 genomes within five years — cheaper than many medical tests.
But he cautions that the technology is moving faster than scientists' ability to extract useful information from the 25,000 genes and 6 billion bits of biochemical data that make up every human genome.
Until recently, only about 20 human genomes had been fully sequenced, all from healthy people. ISB's family genomes, and the genome of a prominent geneticist with a rare nerve disease reported this week by scientists at Baylor College of Medicine, are the first efforts to begin searching for useful medical insights in the genomes of people with illness.
University of Washington pediatrics professor Dr. Michael Bamshad, a co-author of the study, had been working with the family at the heart of the new analysis. While both parents are healthy, the two now-adult children have the drooping eyelids, small cheekbones and other facial and limb deformities characteristic of Miller syndrome.
The children's stepfather is a geneticist at the University of Utah and a co-author of the study. In an interview with The Salt Lake Tribune, Debbie Jorde, the children's mother, said the family wanted to help others by sharing their genetic information.
Her son is now 29 and suffers from chronic back pain. Her daughter is 33. The siblings have undergone a combined total of 50 surgeries, the Utah paper reported.
Experts have long known that Miller syndrome is genetic. But they had never been able to pinpoint the gene. Having genomes from all the family members allowed the Seattle team to focus on identical genetic sequences in the two children. That helped shrink the genetic haystack from thousands of genes to four likely targets.
"If you have both the parents and the kids, you can lay it all out," Galas said.
A UW team was actually first to identify the Miller syndrome gene, working with genetic material from the same children. Instead of searching the entire genomes, the UW scientists analyzed a smaller subset of DNA. But they kept their findings secret from their ISB collaborators, to ensure that each team zeroed in on the same gene independently.
Having their genomes sequenced hasn't led to any new treatments for the children, Bamshad said.
The lack of cures and therapies arising from the original human-genome program has been a disappointment to many. But as more genomes are sequenced and studied in detail, scientists will learn more about how diseases work and how to short-circuit them, Galas said.
Comparing genome sequences, particularly among family members, will be a powerful way to search for the multiple genes believed to play a role in many medical problems, from heart disease to rheumatoid arthritis, Galas said. He and his co-workers plan next to sequence genomes from extended families with a high rate of Alzheimer's disease.
ISB's co-founder, Leroy Hood, was a pioneer of genome sequencing. The automated DNA sequencers he developed in the 1990s revolutionized the field.
But those machines are now as obsolete as electric typewriters. Rather than invest in new-generation machines that will themselves be outdated soon, the ISB team opted to outsource their genome sequencing to Complete Genomics, one of several commercial enterprises poised to start cranking out genetic sequences.
The ISB family project was the California company's first customer, said Chief Executive Clifford Reid. He expects his "factory" to soon begin producing 500 genomes a month. Most will initially go to research labs. But as prices fall, Reid expects to get orders from companies that offer full genome sequencing direct to the public.
Sandi Doughton: 206-464-2491 or firstname.lastname@example.org
Information in this story, published Mar. 10, was corrected Mar. 19. The genome of the prominent geneticist was reported by scientists at the Baylor College of Medicine. A previous version stated the scientists were from Baylor University.
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