The number of genetic variants which are related to risk of multiple sclerosis has just doubled. Given the continued rapid rate of decline in the costs of genetic testing and genetic sequencing the corresponding explosion in genetic discoveries as in this report should not come as a surprise.
Dr. John Rioux, researcher at the Montreal Heart Institute, Associate Professor of Medicine at the Université de Montréal and original co-founder of the International Multiple Sclerosis Genetics Consortium is one of the scientists who have identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of a very debilitating neurological disease. Many of the genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.
The research, involving an international team of investigators led by the Universities of Cambridge and Oxford, and funded by the Wellcome Trust, was published today in the journal Nature. This is the largest MS genetics study ever undertaken and includes contributions from almost 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.
That many of these genes play a role in immune function adds support for the theory that M.S. is either an auto-immune disorder or some other malfunction of the immune system.
At least 29 new genetic associations were added to the existing 23 known genetic associations with M.S.
In this multi-population study, researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.
It used to be the case that just finding one genetic association was a big discovery. Now a single study turns up at least 29 associations and 5 more suspected associations. That's what happens when the volume of data that can be collected goes up by orders of magnitude due to due to orders of magnitude declines in genetic sequencing costs.
Another recent study on genetic influences on intelligence provides another illustration of how cheap DNA testing technology has made large scale searches for genes that each play small roles in some attribute or disease.
Rapid advances in technology have improved the efficiency and dramatically lowered the cost of genome-wide scans like the one conducted by Deary and colleagues.
“We now have the tools to look at large numbers of genes in large numbers of people at the same time,” says Julio Licinio, MD, of Australia’s National University Canberra.
The brain gene scan for intelligence only used 3500 subjects. Since the genes contributing to intelligence are suspected of being large in number with each playing only a small role it is necessary to use hundreds of thousands or millions of people to identify each of the genes that contribute to intelligence. But given the continued rapid decline in genetic technology that scale of research is going to become possible in a few more years. Our Dark Ages of understanding of human genetics is about to come to an end.
DURHAM, N.C. – New genomic analyses suggest that the most common genetic variants in the human genome aren't the ones most likely causing disease. Rare genetic variants, the type found most often in functional areas of human DNA, are more often linked to disease, genetic experts at Duke University Medical Center report.
We all carry at least hundreds of rare genetic variants. So one has to read "rare" to mean that each rare variant is not covered by large numbers of people even though the total number of rare variants is very high.
These results make sense because any genetic variant that makes a big negative impact on health will usually get selected out of a population before the variant spreads to large numbers of progeny.
The study was published in the American Journal of Human Genetics on March 31.
"The more common a variant is, the less likely it is to be found in a functional region of the genome," said senior author David Goldstein, Ph.D., director of the Duke Center for Human Genome Variation. "Scientists have reported this observation before, but this study is the most comprehensive effort to date using annotations of the functional regions of the human genome and fully sequenced genomes."
Goldstein said that "the magnitude of the effect is dramatic and is consistent across all frequencies of variants we looked at." He also said he was surprised by the notable consistency of the finding. "It's not just that the most rare variants are different from the most common, it's that at every increase in frequency, a variant is less and less likely to be found in a functional region of the DNA," Goldstein said. "This analysis is consistent with what appears to be a growing consensus that common variants are less important in common diseases than many had originally thought."
This makes the discovery of the genetic variants that impact disease risks much harder to do. The number of disease-risk influences is much larger. Each variant has very few people carrying it. So there's less of a mutual benefit when each harmful variant is found.
This result is an argument for allowing the general population to spend their own money to get themselves genetically tested and sequenced. They can then submit their own genetic test results and disease history to medical genetics research groups for study. To discover all the genetic variants that influence disease risks will require most of the population to get themselves genetically tested and then to share their genetic test results with medical genetics researchers.
A collaborative team of scientists and physicians at the Medical College of Wisconsin and Children's Hospital of Wisconsin uses genetic sequencing to identify and treat an unknown disease.
For the one of the first times in medical history, researchers and physicians at The Medical College of Wisconsin and Children's Hospital of Wisconsin sequenced all the genes in a boy's DNA to identify a previously-unknown mutation. The team was able not only to identify the mutation, but to develop a treatment plan using a cord blood transplant, and stop the course of the disease.
The poor little 3 year old, Nicholas Volker of Monona, Wisconsin, had already undergone 100 (!) operations for his disease. After sequencing his genome and spending 3 months looking for potential candidate mutations the researchers narrowed in on a mutation, decided on a cord stem cell transplant, identified a compatible donor, and did the transplant. Now the little kid is at home and eating a normal diet without further symptoms of bowel disease. Amazing.
This result is a sign of the times. Where sequencing a full genome took years and hundreds of millions of dollars back in the 1990s it now takes at most a couple of tens of thousands of dollars for a fast sequencing. The trend on DNA sequencing costs is down, down, down. In the next few years costs will drop below $1000.
If you want to be an early adopter of genetic testing technology you ought to think seriously about getting yourself tested in 2011. The early adopter phase for genetic testing won't last more than another year or two. The full genome sequencing early adopter phase will probably run a few years longer. I'm planning to get full genome sequencing done in 2013 or 2014.
The cost of genome sequencing has now fallen far enough that scientists are able to sequence the entire genome of people with rare genetic diseases to identify their causes.
James Lupski, a physician-scientist who suffers from a neurological disorder called Charcot-Marie-Tooth, has been searching for the genetic cause of his disease for more than 25 years. Late last year, he finally found it--by sequencing his entire genome. While a number of human genome sequences have been published to date, Lupski's research is the first to show how whole-genome sequencing can be used to identify the genetic cause of an individual's disease.
The project, published today in the New England Journal of Medicine, reflects a new approach to the hunt for disease-causing genes--an approach made possible by the plunging cost of DNA sequencing. Part of a growing trend in the field, the study incorporates both new technology and a more traditional method of gene-hunting that involves analyzing families with rare genetic diseases. A second study, the first to describe the genomes of an entire family of four, confirmed the genetic root of a rare disease, called Miller syndrome, afflicting both children. That study was published online yesterday in Science.
For some genetic diseases there's not just one mutation that causes them. Lupski got 2 different rare mutations from his parents. Several other mutations are known to cause his neurological disorder Charcot-Marie-Tooth.
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.
At what price would you get your full genome sequenced? Your answer probably depends in part on what you expect you'll be able to do with the information in your daily life. The identification of genetic sequences that determine the ideal diet would certainly make a full genome sequencing worth at least $250 to me.
The sequencing of Lupski's genome turned up hundreds of thousands of genetic differences not yet identified in other humans. As the total pool of fully sequenced genomes grows the number of new mutations found will decline with each new genome added.
On a more philosophical note, the whole genome sequencing provided Lupski clues to what makes an individual.
"My genome has 3.5 million differences from the reference genome (sequenced in the original human genome project)," he said. "I have hundreds of thousands of differences from all the other genomes that have been sequenced. I expect that to hold true for others. Everyone is truly unique."
Led by scientists at the Seattle-based Institute for Systems Biology, the study, published Thursday, March 11, 2010 in Science Express, sequenced the entire genome of a family of four—the parents, daughter, and son. By comparing the parents' DNA sequences to those of their children, the researchers estimated with a high degree of certainty that each parent passes 30 mutations—for a total of 60—to their offspring.
Scientists long had estimated that each parent passes 75 gene mutations to their children.
Most of these new mutations probably have no functional significance. But trying to tease out which mutations cause differences in our health or abilities is really hard to do for most mutations. If a mutation causes only a small difference in health or ability and very few people carry it then it is hard to compare people to detect a difference caused by that mutation.