When Geneticists Unite

I've just realized (read: decided not to ignore) the fact that I haven't posted in many months. Going nearly five months between updates is not a very good start at attempting to become a blogger/science writer. So today begins attempt #6 at writing about science and to get the ball rolling on this website. This week I'm attending the American Society of Human Genetics (ASHG) annual conference. In a stroke of luck the conference is being held in downtown Baltimore so I get to sleep in my own bed and walk to work all week - heaven.

Clearly there are a lot of geneticists here, with too many opinions sometimes. And although there are countless seminars and talks and symposiums at this year's event, I feel there has been a very clear message broadcast as the 'unofficial' theme: communication. I'm not sure that was intended or not, but many investigators and clinicians (even patients) are stressing the importance of more communication between researchers and community. Taking that to heart I've decided to provide a little update about my experience at the conference and 'communicate' some of the coolest things I've stumbled upon while here. So without further ado I'd like to present my first offering.

Enter Mr. Robot:

I'm sorry for the potato - quality image. I still don't know how to use my phone's camera appropriately even though I've had it for four years or so. Regardless, this robot runs automated PCR assays for companies and university laboratories. (If you don't know what PCR is, please read my previous post on the subject called The Next Revolution in Genetics). The company (Hitachi) selling these bots is from Japan and they have been using these guys for several years now. Each eyepiece contains a small camera and its hands are quite dexterous, yet sturdy and completely automated. The representative I was speaking with said they were looking to enter the American market and in a few years it is conceivable that many major universities and companies, which run thousands of PCR reactions, will be using these to provide faster and cheaper sample processing. I have mixed feelings about this technology. Clearly it's bad-ass and the robot is friendly-looking enough. In fact it reminds me a little bit of WALL-E. But I can't help but wonder how many lab techs and post-bacs (or even post-docs) will be facing an even more competitive environment where jobs are no longer needed to run large research and gene-sequencing initiatives. It's a changing world. 

The Next Generation - The Genome vs. The Exome

Most people know what the genome is. Simply, the genome is the collection of your DNA's entire genetic sequence. From the sequences that make up your genes, to the regulatory elements that govern how your genes are expressed, and finally the long stretches of DNA that have few genes but which are still vitally important structural elements. Your genome is the complete package of DNA that is found in nearly every cell of your body (mature red blood cells do not have a nucleus and little to no DNA).  

What you may not be as familiar with is the exome. The exome is a little trickier to identify, but when analyzed it can provide important clues into your health and where/when specific genes are expressed.  When a gene from your DNA is expressed, an RNA copy is made. RNA is a nucleic acid, similar to DNA, and acts as a middle man between DNA and ultimately the proteins that are created. All proteins are coded for by DNA genes, and all proteins arise from the edited RNAs that carry the 'message' of your DNA to the machinery that makes the proteins. (There are many additional types of RNAs that don't code for proteins but that is a story for another post.) The RNA, called messenger RNA or mRNA, is edited and processed, not unlike editing down a blog post from a draft to something (hopefully) legible. The cell then reads the processed mRNA to create our proteins. The exome is all of the RNAs expressed at a specific point of time in a specific tissue. For instance, the exome of your neurons would be all those RNAs found in your neurons at the time when it was collected. The exome gives us insight into the exact library of genes that have been turned on specifically in the neurons....or within a tumor...or any other type of tissue being tested. 

Our bodies have tens of thousands of genes (~25-30,000 protein-coding genes and another 10-20,000 non-protein coding genes that code for additional RNAs). Amazingly, our bodies have evolved to be masters of efficiency. We simply don't need to express every gene/protein in every cell of our body. Proteins required for the function of the heart, and not at all for the function of the liver, are simply not expressed in the liver. There are liver proteins found in the liver but not in the heart. And even though every cell in our body has the complete DNA 'blueprints' for the entire body, tissues and specific types of cells are good at maximizing and expressing only those genes and proteins essential for its own normal function. By sequencing our exome in a particular tissue, we get a specific answer on what exactly is going on with our expressed genes in said tissue. This also allows us to cancel out all the other background genetic 'noise' that isn't important. 

Many genetic mutations arise de novo - meaning they are brand new to an individual and not inherited from parents. Many disease are caused by de novo mutations, including cancers. Clinicians can make use of this by comparing and contrasting normal tissue in your body with diseased tissue (there are many ways to make this comparison, sequencing the genomes vs the exome is only an example). Companies can sequence your genome from your blood immune cells (in which case your entire genetic sequence is known) and then sequence your exome from a cancerous tissue (in which only those genes expressed in that particular cancer tissue are sequenced). Then, the results can be matched together and mutations potentially identified. In the dawn of personalized medicine, this allows clinicians to zero in on whether your genome has a mutation in an important gene....ideally tailoring a therapy specifically for you. Whole genome sequencing can also tell us whether a variation in your DNA is the result of inheritance from mom or dad, or one that developed de novo when you were growing in the womb. 

Below is a genetic testing kit that I got this morning from Centogene - a biomedical company based in Germany. Clinicians can order a genetic sequencing test of either your genome or your exome to identify variations in your genetic sequence that may influence disease: such as in the BRCA1 gene.  

And here is a picture of where your blood is dropped and dried and sent for analysis (note the circles):

This genetic test requires only 50 micro liters of blood (literally just a few drops) and costs only $2000. To put that in perspective, ten years ago sequencing of one individual cost millions of dollars. So the technology and the cost are both dramatically improving and I thought it would be good to show that we are very close to knocking on the door of the $1,000 genome (the gold standard). 

Now back to where communication comes in. Many patients and those outside of science confuse the genome with the exome (for good reason as they are very related), or what a genetic test can definitively tell you. It's the job of scientists, doctors, and those in medicine to clarify these differences so that patients know exactly what they are getting. It's also our job to show politicians on the Hill just how advanced technology is, why a new age in medicine is on the horizon, and why we need to continue to propel this forward with increased funding and discussion with all members of the community. 

And to put a cherry on top, below is one last photo from the event so far. I'm a sucker for the stress-ball giveaways from the vendors. I have a large collection of them at work (I don't know why...maybe I'm stressed?). This is a picture of the one that is by the far the best I've ever received - a squishy sperm cell. Who wouldn't want that on their work desk?