2010 June 24 Thursday
More Human Genetic Variation Found Than Expected

Jumping genes are jumping all over human genomes. They are out of control. Though some (probably most) of those jumps to new insertion points do not cause any functional differences.

Scientists are finding more variation in the human genome than they had previously expected, now that new technologies are allowing researchers a closer look at the genomes of many individuals, according to a new study from University of Maryland School of Medicine researchers. The study, to be published in the June 25 issue of the journal Cell, is one of the first to take an in-depth look at transposons, known as "jumping genes."

Transposons are segments of DNA that can replicate themselves meaning that each generation of a human family has more transposons in its genome than its ancestors and move to new sites in each individual person's genome. The researchers examined the genomes of 76 people and found that new occurrences of transposons were surprisingly prevalent. They also found that transposons are very active in lung cancer genomes.

I've never bought the "we are all genetically very similar" argument trumpeted in early announcements of progress in human genome sequencing. We are all too different in too many ways for that to be the case. I expect the discovery of lots of mutations that adapt people to fairly small ecological niches such as adaptations to better metabolize particular types of food.

More advanced genetic sequencing technologies made this new discovery possible. Such advances will continue at a rapid rate until genetic sequencing becomes extremely cheap and most people get full genome sequencing done on them.

"A key part of this study was that we developed new, next-generation sequencing and informatics technologies that allowed us to look at these variants for the first time in many human genomes," says Scott E. Devine, Ph.D., an associate professor at the University of Maryland School of Medicine and a research scientist at the school's Institute for Genome Sciences.

More data, faster and cheaper. That's the way it is going in genetics.

If you can spare $10k you can get yourself sequenced. Though note that today's sequencing technologies won't catch all the large copy variations. You'll be able to get a much better sequence of your full genome in a few years.

Technological advances in DNA sequencing have made it possible to examine transposons in greater detail, Dr. Devine adds, and also have cut the cost of sequencing a human genome from millions of dollars just a few years ago to as little as $10,000 now.

The cheaper sequencing gets the more that sequencing data will be correlated with intellectual characteristics, physical appearances, and other characteristics. Some time in the next 10 years the amount of information available from sequencing will become great enough to make it worthwhile for individuals to pay to get sequenced.

We might each have our own unique jumping gene difference.

Transposons, or "jumping genes," make up roughly half of the human genome. Geneticists previously estimated that they replicate and insert themselves into new locations roughly one in every 20 live births.

New results, published in the June 25, 2010 issue of Cell, suggest that every newborn is likely to have a new transposon somewhere in his or her genome.

"Now it looks like every person might have a new insertion somewhere," says senior author Scott Devine, PhD, associate professor of medicine at the University of Maryland School of Medicine's Institute for Genome Sciences. "This is an under-appreciated mechanism for continuing mutation of the human genome."

Here's where I think one of the biggest payoffs will come in the next 10 years from all the DNA sequencing work: figuring out the mutations that make each tumor spread.

Devine's team also showed that transposons frequently jump to new locations during the process of tumor formation. Surveying 20 lung tumors and comparing their genomes against the normal tissues they came from, the team found that six tumors had new transposon insertions that were not present in the normal adjacent tissues.

Cheap DNA sequencing will enable the sequencing of each tumor's cells. Treatments will become customized to aim at the mutations found in each tumor. Personalized cancer treatment will be the order of the day. Viruses or other packages will carry pieces of DNA or RNA into cancer cells to silence cancer-promoting genes or to order only cells with cancer-causing mutations to commit suicide.

Crowd sourcing with self-reported health data compared with genetic testing data can speed up discovery of genetic associations.

MOUNTAIN VIEW, CA (June 24, 2010) 23andMe, Inc., a leading personal genetics company, announced today that it has published the first data to come out of its novel participant-driven research program. The results, available online in the journal PLoS Genetics, replicate several known genetic associations, validating 23andMe's methodology and ushering in an era of more efficient genetic research.

"This paper announces and validates a revolutionary way of conducting scientific research," said Anne Wojcicki, 23andMe President and Co-Founder. "In this paper we confirm that self reported data from our customers has the potential to yield data of comparable quality as data gathered using traditional research methods. We are excited about moving scientific research forward, faster," continued Wojcicki.

Imagine how much faster the associations between genetic sequences and human differences will be accelerated once millions of genetic differences are know for each of tens and hundreds of millions of people.

By Randall Parker    2010 June 24 10:23 PM   Entry Permalink | Comments (1)
2008 July 23 Wednesday
Myopathy From Statins Due To Rare Gene

Statin drugs (e.g. Lipitor, Crestor, Pravachol) are widely used to lower cholesterol but occasionally cause worrisome side effects including muscle pain and weakness. A discovery shows that a genetic test could reveal high risk people who can avoid muscle problems by refraining from statin drug use.

The researchers, funded by the British Heart Foundation (BHF), found a variation in the DNA code of a gene called SLC01B1 was responsible for 60% of the myopathy cases in people taking high dose statin therapy.

SLC01B1 regulates the uptake of statins into the liver, and the genetic variant seems to affect its function, causing higher levels of the statin to be present in the blood.

Only about one in 10,000 patients taking a standard dose of statins develops myopathy, and the risk remains very low even if they carry the rogue gene.

This one genetic variant does not explain all cases of muscle problems in response to statin drug use.

Many drugs have failed in advanced stage clinical trials because they caused dangerous and even deadly side effects in small but significant portions of drug trial participants. The continued decline in the costs of genetic testing will allow many of those side effects to be traced back to genetic variants found in some but not all people. So drugs which would otherwise fail clinical trials will instead emerge with restrictions on the genetic profiles of potential users.

The ability to identify who will have dangerous side effects from drug use will enable more drugs to reach the market. Also, research on genetic profiles and drug efficacy will also reveal genetic profiles that work better or worse with particular drugs. The matching of genetic profiles to drug choices will some day become commonplace.

By Randall Parker    2008 July 23 11:06 PM   Entry Permalink | Comments (1)
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