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  • Napoleon in Shanghai
    by Will Frehley. If leadership is genetic, what sort of DNA should a charismatic robot have?

Al Gore's DNA

Former vice president Al Gore recently helped launch Navigenics, a new personal genomics service.  According to Gore, "on all these new genetic breakthroughs, there is always some resistance culturally, and then, where there's an evaluation of the inherent value, if the ethics are right, if the surrounding culture is right, then it just breaks through ... I think it's going to be a fantastic success."

Using Navigenics' service, you can determine your projected lifetime risk for certain conditions like heart disease, based on your personal genetic differences.

The Personal Genome Project

Harvard's George Church (with help from Google) plans to identify the genetic variations of 100,000 people (and perhaps eventually 1,000,000 people), and associate their gene variants with their health and family disease history.

According to a recent article in Bloomberg:

By matching genetic data from each person with his or her health history, Church would build a database that would link DNA variations and disease for scientists and drugmakers, the first step in deciding on treatments that can block the mutations or adjust how they work within the body. Church also said he'll explore other human traits under genetic control. Participants will give facial and body measurements, tell researchers what time they get up in the morning, and detail other behaviors, he said.

Previously, it's been difficult for scientists to determine which specific gene variants are responsible for disease, without having this much data to analyze.  There are 3 million "single letter" DNA differences between people (which account for 10% of the total genetic variation).  In order to make statistically valid associations between genetic variation and disease, you need to study the gene variants of hundreds of thousands (if not millions) of people.

Google_dna Google is positioning itself to help consumers keep track of their complex genetic data, and self-manage their electronic healthcare records.  The U.S. Congress is lagging behind the rapid technology advances, and should immediately pass legislation that prohibits any genetic discrimination, especially by insurance providers.

What is a Chimera?

According to the New England Journal of Medicine, a woman named Lydia Fairchild gave birth to her own child in 2002, but genetic tests performed on her skin and hair did not match her child (except to the degree a grandmother might match).

However, DNA from other tissue in Fairchild's body did match her child. Lydia carried two distinct sets of DNA within her body, the defining characteristic of a chimera.

Chimera2_2 The most likely explanation is that Lydia Fairchild herself was a fusion of two sets of chromosomes from her parents, when she was born. Her mother simultaneously ovulated two eggs, which were both fertilized by different sperm from her father.  Then the two eggs fused into a single embryo, which grew up to be Lydia.

In other words, as Lydia Fairchild developed, both types of cells within her participated in constructing her various organs, but not all the DNA was represented in all her organs.  She had two distinct sets of DNA, as if she had twins inside her own body.

So when Lydia Fairchild had a child of her own, the child inherited one set of her DNA, but not the other set.

How many genes does it take to create life?

Mp_3 How many genes does it take to create life? Mycoplasma genitalium bacteria has 485 genes, and this is the fewest for any free-living organism. But 103 of its genes can be individually removed without killing it, so 382 genes seem to be essential for life.

At the J. Craig Venter Institute, scientists are assembling those 382 genes from scratch to synthesize new organisms. Their hope is to insert additional genes along the way, to generate useful bi-products.  Synthetic bacteria with added genes could become "trillion dollar organisms". For example, large vats of "enhanced" bacterium could produce bio-fuels (or any other organic product), and launch entirely new industries.

1000 Genomes Project

An international research consortium has announced it will sequence the complete DNA of 1,000 people.  The goal is to "catalog [DNA] variants that are present at 1 percent or greater frequency in the human population". The project will focus not only on mapping single-letter differences in DNA, but also "structural variants" such as DNA rearrangements, deletions or duplications of segments.

According to ScienceDaily: "It is important to understand the small fraction of genetic material that varies among people because it can help explain individual differences in susceptibility to disease, response to drugs or reaction to environmental factors."

Effects of variations in your DNA

If you like Wikipedia, you'll love the new SNPedia, which lists the effects of variations in your DNA (known as SNPs). Want to know what gene variants you have? Subscribe to 23andme.com. For the intrepid, you can also try the new Personal Genome Explorer.

Dusty old volumes from our Genetic Library

Library It seems that the process of evolution makes good use of old knowledge, stored away in our DNA library.  A new study shows how ancient DNA fragments (which are really just encapsulated knowledge from the pre-historic past) can be revived and applied, to design new forms of life, through changes to the genetic regulatory system.

Apologies for my lack of posts recently.  I'm writing a novel, based on this blog!  Should have something to show for it in the next month or two.

Genome-wide Association Studies (GWAS)

Genome-wide association studies are all the rage now.  With the availability of new gene chips that can Short_tall cheaply and efficiently measure millions of genetic differences between individuals, it's now possible to associate observable traits (among a group of 5,000 or 30,000 or more human subjects) with their specific gene variants.

You need to study a lot of people (a large sample size) before you can confidently determine which gene variant does what.  These new cheaper gene chips allow for such large studies to be run, and the gene variants of thousands of people to be analyzed and compared.

For example, a recent study shows that having a variant of the HMGA2 gene can make you half a centimeter taller or shorter (depending on the HMGA2 variant you possess).

So what's the use of having this information?  Can you change the outcome?  Not really.  Since this is clearly a "development gene", you wouldn't be able to affect the outcome in height after you're fully grown.  You could intervene at an early age, by determining which gene variant you have, and bolstering your size with a regimen of human growth hormone (hGH) if you're not happy with the natural developmental outcome.  But you'd be too young to make that decision for yourself.

Consumer genetics

A number of companies now offer affordable genetic tests for consumers.  DNA Direct offers disease-related gene tests in the $200-$500 range.  And IBM’s popular Genographic Project kit allows individuals to trace their genealogical history for $99.

Now (according to a recent story) a Google-backed company (23andMe) has joined forces with Illumina - a maker of "gene chips" - to identify 550,000 genetic differences between individuals (for around $300-$600).

Mousedna The function of all these genetic differences are not yet known, of course.  But the more people who get measured, the larger the sample size, and the more statistically relevant the results will be.

So what if you send a sample of your blood to 23andMe?  What happens next?  This is my guess.  I'm imagining they'll measure your unique set of 500,000 or 1 million genetic differences, and record them in a database.  Then they will send surveys to everyone in their network (who submitted a sample), to ask about their family history of disease, etc.  Once a million or more people join their network, the correlation between the responses to the survey ("my father had colon cancer") and the specific genetic differences for those response (e.g. "Gene X") will be much easier to accurately judge.

I'm not cynical about this.  I don't think 23andMe will try to sell your personal genetic information.  They are simply trying to learn about diseases correlated with genes (which they plan to share, and thus facilitate treatments).  They will need a lot of data to make the association (since there are so many possible genetic differences).  It's an exciting prospect, but we must ensure that our laws keep up with the science, and absolutely forbid any sort of genetic discrimination on a personal basis.  They data should be kept in an aggregate form.

RNA, it's the new DNA

The central dogma of genetics used to go something like this: Our genes (DNA) are transcribed into smaller pieces (RNA), which are then translated into the proteins that build our body.

Dogma Now it's looking like that old dogma just won't hunt. (Apologies for a bad pun at the expense of the scientific method, that great, messy, wonderful process -- just like democracy!)

Previously, scientists thought each of our genes acted as a blueprint for a single protein.  Then they discovered that single genes may be alternatively spliced into different RNA transcripts, resulting in different proteins from the same gene.  But they still claimed that only 5% of our genetic material was being used to encode for proteins, and the other 95% of the gene was snipped out in the transcription process, relegated to the cutting room floor as junk DNA.

Recently, however, a group of scientists comprising the ENCODE project decided to look more deeply into this puzzle, by examining 1% of our DNA in more detail.  And they found clues for what the other 95% of our DNA does.

According to Thomas D. Tullius, professor of chemistry at Boston University and one of the ENCODE researchers

"There were huge surprises; this research has upset a lot of thinking about how the genome works." ... "There now appear to be thousands of places in the genome that were long thought to be useless or meaningless [junk DNA], but which we now see to have a functional role. But we don't really understand what that role is."

Other interesting findings:

The new work suggests that the "control regions" in the DNA are far more extensive, perhaps embracing more than half of all DNA. Functions thought to be carried out by genes alone now appear to be managed by multiple, overlapping segments of DNA. In addition, other portions of the genome are believed to be on standby, as a toolbag to be utilized as humans evolve.

Dna3_2 The ENCODE project found that much of our DNA doesn't code for proteins at all, but instead is transcribed into specialized microRNA molecules that may be just as interesting as DNA and proteins. These are scnRNAs, snRNAs, snoRNAs, rasiRNAs, tasiRNAs, natsiRNAs and piRNAs.

MicroRNAs seem to act as behind-the-scenes puppetmasters, helping to regulate protein activity. For example

Dave Bartel, of the Massachusetts Institute of Technology ... discovered microRNA genes interspersed among sets of protein-encoding genes called Hox clusters. Hox clusters contain basic instructions about body plans, and the genes within them are arranged in the order in which they influence their owner's shape during development. In short, a Hox gene at one end of a cluster contains the information: “Give this embryo a head”. The gene at the other end says: “And a tail, too”. The role of the interspersed microRNAs is to regulate these high-level commands.

Ronald Plasterk, of the University of Utrecht, in the Netherlands, suggests that microRNAs are important in the evolution of the human brain. In December's Nature Genetics, he compared the microRNAs encoded by chimpanzee and human genomes. About 8% of the microRNAs that are expressed in the human brain were unique to it, much more than chance and the evolutionary distance between chimps and people would predict.

RNA also opens up a mechanism for Intelligent Design because:

small RNAs are active in cells' nuclei as well as in their outer reaches. Greg Hannon, of the Cold Spring Harbor Laboratory in New York State, thinks that some of these RNA molecules are helping to direct subtle chemical modifications to DNA. ... They thus change the effective composition of the genome in a way similar to mutation of the DNA itself (it is such mutations that are the raw material of natural selection)....

RNA could itself provide an alternative evolutionary substrate. That is because RNA sometimes carries genetic information down the generations independently of DNA, by hitching a lift in the sex cells.