19 March 2010

Variability in Transcription Factor Binding Can Make You Look Like a Monkey if You Pay for Expensive Gene Sequencing

The ready availability of gene sequencing promises to bring in a new era in medicine.  But expensive gene sequences may not tell you what you really want to know.  Underlying phenomena such as transcription factor binding, non-coding RNAs, copy number variant, and other more shadowy aspects of gene expression may hold the secret keys to more subtle aspects of why you are the way you are.
"We are rapidly entering a time when nearly anyone can have his or her genome sequenced," said Michael Snyder, PhD, professor and chair of genetics at Stanford. "However, the bulk of the differences among individuals are not found in the genes themselves, but in regions we know relatively little about. Now we see that these differences profoundly impact protein binding and gene expression."

Snyder is the senior author of two papers -- one in Science Express and one in Nature -- exploring these protein-binding differences in humans, chimpanzees and yeast. Snyder, the Stanford W. Ascherman, MD, FACS, Professor in Genetics, came to Stanford in July 2009 from Yale, where much of the work was conducted.

Genes, which carry the specific instructions necessary to make proteins do the work of the cell, vary by only about 0.025 percent across all humans. Scientists have spent decades trying to understand how these tiny differences affect who we are and what we become. In contrast, non-coding regions of the genome, which account for approximately 98 percent of our DNA, vary in their sequence by about 1 to 4 percent. But until recently, scientists had little, if any, idea what these regions do and how they contribute to the "special sauce" that makes me, me, and you, you.

Now Snyder and his colleagues have found that the unique, specific changes among individuals in the sequence of DNA affect the ability of "control proteins" called transcription factors to bind to the regions that control gene expression. As a result, the subsequent expression of nearby genes can vary significantly. _SD

The Stanford team is only scraping the surface of the complexity of gene expression, but they are making progress. For members of the public it would be easy to become obsessed with the marvels of gene sequencing, and to overlook the fact that the gene sequence is just the bare beginning of understanding gene expression. A crucially important beginning, yes, but still a small one.

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Blogger Life & things.... said...

The fact that "The ready availability of gene sequencing" is an eye opener for me. I was under the impression that this sort of thing was only for Bond movies !
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Friday, 19 March, 2010  
Anonymous Anonymous said...

@Life & things...
I think that complete personal sequencing is still kind of expensive and not yet a marketable service since the practical benefits are still in early days but the ability to sequence a genome is getting much less expensive and much faster, with even better techniques coming through the development process.

@Al Fin
Your point about the importance of controling elements associated with genes is dead on. But unfortunately, a lot of the important regulation gets performed during embryonic development or is influenced by surounding tissue so if you want a prehensile tail you are going to need to kick start the process with some tissue engineering using stem cells. A growing understanding of these regulatory elements will make such tissue engineering possible and help create patient specific stem cells and guide their development in desired directions.

One of the interesting things about these control mechanisms is that genes can be tested to see if they behave differently in adult animal models. Previously, if you knocked out a gene in a mouse embryo, you would only know what it did if its loss was not fatal to the embryo. But they are now able to "silence" a gene after the organism has undergone development which can provide more insight into how the gene functions when development is complete.

Saturday, 20 March, 2010  
Anonymous Anonymous said...

P.S. I know you aware of the issue of embryonic and neighboring tissue on gene regulation. I only point it out for the benefit of others who might want to start saving up for their monkey pills. So be warned everyone; you are going to need to budget for some surgeries and other added expenses. Prehensile tails don't grow on trees you know.

Saturday, 20 March, 2010  
Blogger al fin said...

Baron, your point about the prehensile tail is duly noted.

Most human monkeys -- college professors for example -- do not have such obvious visual indicators. You have to listen to them talk to place them in the proper category. Unfortunately, a large proportion of young students lack the experience to categorise the academic monkeys who are teaching them, and end up becoming monkeys themselves.

Sunday, 21 March, 2010  
Blogger Jim Richardson said...

Wow, technology these days. I really do need do a lot of keeping up! I was even astound how many online MBA programs are now available in the internet. It just makes deciding on which program is the best more complicated. This is very interesting. I didn’t know this can be possible now. But I was just wondering why do people need to go for gene sequencing? What is it for? I’m just really curious about it. Thank you for this blog! I’m glad that I came across your site. I’ll be happy to read more interesting articles from you.

Friday, 08 October, 2010  

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