From Californians’ DNA, a Giant Genome Project (NYT 28/5/10)
Still in fine fettle at the age of 87, Ruth Young, a retired Oakland school nurse, jumped at the chance, she said, to “spit for the cause.”
Mrs. Young is one of more than 130,000 members of Kaiser Permanente in Northern California who have volunteered to have their DNA scanned by robotic, high-speed gene-reading machines as part of the largest human genome study of its kind ever attempted.
The goal of the study they are participating in is to help scientists uncover the genetic roots of chronic disease and, perhaps, to find out why some people live longer than others.
This month, researchers at Kaiser Permanente in Oakland and the University of California, San Francisco began the highly automated, large-scale process of analyzing that DNA, which is being extracted from tens of thousands of saliva samples donated by Kaiser members in Northern California since 2008.
Each sample of ordinary spit is laden with cells containing the volunteer’s entire set of genes, their genomes, which carry in sequences of DNA the coded instructions for building and maintaining life. The hope for this so-called genome-wide association study is that, when the genes of people with diseases like cancer and multiple sclerosis are compared with the genes of those in good health, computer analysis will pinpoint genes responsible for the illnesses.
With a speed that would have seemed preposterous to contemplate a decade ago, the work of collecting, purifying and digitizing billions of discrete bits of chemical information will be finished in less than 18 months, providing a rich resource for scientists to analyze for decades to come.
Winifred K. Rossi, who is managing the project for the National Institute on Aging, said most genome-wide association studies scan between 5,000 and 8,000 participants, although data from multiple, smaller studies can be pooled to form a larger group. What makes the Kaiser study unique is that members of a single, colossal cohort will have their genomes scanned uniformly, then paired with their medical histories. “It is absolutely the largest study of its kind, and it has enormous statistical power.” Ms. Rossi said.
Mrs. Young, a Kaiser member for 63 years, suffers from arthritic knees and Type II diabetes, which took her father’s life at an early age. “I’m conscientious about my diet, but I do love sweets,” she said.
She had originally been one of nearly two million patients asked in 2007 about participating in the Kaiser study. A huge group of volunteers, ranging in age from 18 to 107, filled out questionnaires. Tens of thousands of them, like Mrs. Young, were asked for specimens.
Following instructions found in a kit mailed to her Oakland home, Mrs. Young deposited the requested spit into a special plastic cup. She sealed it with a blue lid fitted with a built-in preservative and sent it back to Kaiser. Along with her saliva, the samples from the other 130,000 people began arriving in Kaiser’s mailbox.
Experiments like this one underscore how quickly gene-scanning technology is moving from the lab to the home. Last week, officials of the University of California, Berkeley, disclosed that 6,000 incoming freshman and transfer students will be asked to swab their cheeks at home for DNA, to participate in a collective lesson in genetics and a preview of the predicted era when medicine will be tailored to each person’s genetic makeup.
Each student who agrees to participate will be able to tap in a security code on a laptop and check whether they carry gene variants that might affect their ability to process lactose, alcohol or folate, a vitamin found in leafy greens. The Kaiser study participants will not have the same option. Their names are scrubbed from their samples, and only researchers — working with codes instead of names — will be able to link the gene scans to medical histories. Their goal is to discern the larger picture, hoping to spot associations between genes and health that would not show up until very large numbers of individuals are compared at once.
Although this vast experiment has been contemplated for years, it was given a boost last year when Kaiser and the university won a $25 million grant from the National Institutes of Health as part of the stimulus package.
However, the study has begun just as some scientists have started to question the value of these experiments, and when private ventures, like 23andMe, are struggling to find a consumer market for gene tests.
David B. Goldstein, a Duke University researcher, said he believed “interesting and valuable information” would come from the Kaiser study, but he questioned whether it was the most efficient way to gather information about the genetic links to disease. “It’s an awfully expensive study,” Dr. Goldstein said in an e-mail message.
He added, “We have literally hundreds of genome-wide association studies for common diseases, and in most cases we are having trouble making much use of them.” While Dr. Goldstein stresses that discoveries are being made using that technique, he believes that a different approach — sequencing the entire genetic code of fewer patients rather than scanning the genome for variations — “is likely to yield more useful returns.”
For Kaiser, the federal grant is just the beginning of a long-term endeavor.
In the coming years, 400,000 more members will be asked to contribute their DNA to the project when they come in for routine blood work. Kaiser is spending $9 million to build a repository for the blood samples.
“It’s an idea whose time has come,” said Dr. Pui-Yan Kwok, an investigator at the Institute for Human Genetics at the University of California, San Francisco, where the genes are being scanned. “The genotyping technology is here, the electronic medical records are here.”
Using high-precision robots to process each sample, the genomes of 2,500 participants are being analyzed each week. The genetic information will be stored in computers for future studies by scientists all over the globe.
At the same time, Elizabeth Blackburn, a Nobel-prize winning biologist at the university, and her lab will be conducting a mass experiment on a separate set of 100,000 samples of DNA from the Kaiser patients. They will be measuring the length of telomeres — wads of DNA at the top and bottom of every chromosome that, like shoelace tips, keep them from unraveling when a cell divides. Telomere length tends to shorten with age, and shorter telomeres tend to be linked with shorter life spans.
“Telomere length is more reflective of things that happen in your life than the genetic hand you are born with,” said Dr. Blackburn.
She said that the Kaiser patients are a valuable resource for science because their detailed medical histories can be matched with the varied measurements of telomere length and matched to the gene scans that will be done for each participant as well. Her targets are the three top diseases that kill the elderly: cancer, cardiovascular disease and diabetes.
At the Kaiser research lab, a production line of robotic equipment has been set up to process the 130,000 cups of saliva that have been mailed by patients and stored, at room temperature, in racks of cardboard “pizza boxes,” 50 cups to a box. Here, the robots draw out a sample of spit, and chemically process it to extract the donor’s DNA.
One set of Mrs. Young’s DNA will be sent to Dr. Blackburn’s lab, where the length of its telomeres will be measured. A second set will arrive at Dr. Kwok’s newly equipped facility, where the genome of each Kaiser participant will be scanned using an array of robots, each costing about a quarter million dollars.
At Dr. Kwok’s ninth-floor lab, three sets of robots prepare the DNA samples shipped from Oakland. The full complement of DNA from each volunteer is washed over a custom-designed silicon chip about this size of small fingernail. Microscopic wells etched into the chip are each engineered to pluck out one of 675,000 possible gene variants.
“Our biggest fear is a power-failure,” said Dr. Kwok. Each array, filled with 96 processed DNA samples, costs $10,000.