I’m starting a new company. For now it is called The Geno.me. Our purpose: to develop a highly curated, open-source, easy-to-use Genome Browser that can better help make sense of the mountains of genomic data. We want to make it like GitHub (for those of you who are computer scientists), but for Genomics. Only this way can we truly create an open-source mechanism for attacking the genome.

In the process of coding out our prototype, we’ve discovered so many more issues with the way data is currently stored. You can see a post from a while back where I discuss the incorrect nomenclature of the many monogenic mutations in OMIM. In this current post, I’ll be talking about the issue of gene structures and the way they have been recorded in ENSEMBL.

What are Gene Structures?

On the most basic level, genes are sections of linked nitrogenous bases that are transcribed by RNA polymerase transforming them from DNA to RNA (in humans). Genes are identified as lying within Open Reading Frames (ORFs). Within these ORFs, certain sections of the genes are transcribed into RNA while certain sections are not. Classically, the sections that are transcribed are referred to as exons, and the sections that are not are referred to as introns.

Once the exons are transcribed into RNA, the RNA molecule is then translated into a chain of amino acids. This amino acid chain folds into the proteins that we all know and love. Enzymes, substrates, channels, cell structures, and many more proteins are created in this fashion. The creation process can be summarized as:

DNA (exons, introns) -> Transcription -> RNA  (exons only) -> Translation -> Protein

Congrats. You can now pass Biology 101.

Reality check: For most genes, an ORF contains one more structure besides the exons and the introns – the Untranslated Regions (UTRs). These are regions that are transcribed, but are not translated. See what I did there…I italicized two similar, but importantly distinct words so that we don’t miss this point.

How does ENSEMBL store this data?

Let’s take a gene as a case study: SOD1 (Superoxide Disumtase 1), located on chromosome 21. Here’s an overview of the gene (courtesy of The Geno.me):

In this image, the blue regions represent exons, the gray regions represent introns, and the red regions represents UTRs. In the ENSEMBL structure database, 5 regions are listed. They have grouped the first region (red + blue) into a single entry, as well as the last region (red + blue) into a single entry. They refer to all of them as exons. None of the introns are listed.

While it is very possible to figure out introns based on the location of the exons, this is a mess when dealing with the data. Instead of searching directly for an intron, we must first identify the surrounding exons, etc. The other main problem is that UTRs are not separated from exons! Elsewhere, ENSEMBL lists the positions of the UTRs, but what this means is that in the case of the start and ending exons for this gene, we have to reference many different pieces of data to determine the ultimate structure of the gene! It’s a HUGE headache.

How does The Geno.me fix this problem?

At the genome, we’ve taken care to index every type of gene structure according to its absolute position on the chromosome. In the above picture of SOD1, we count 11 structures (not 5 like ENSEMBL): 2 UTRs, 5 Exons, and 4 Introns. We’ve taken care to do this properly. Introns are structures too.

It’s been exciting building a new genome browser. Anything that annoys us about the old browsers (or quality of data) is within our capacity to correct in a scalable way. If you have any suggestions of features or fixes you’d like added to The Geno.me, please feel free to contact me! The Geno.me is currently in private beta, but if you think your group/lab would be good test dummies for us, go ahead and request an invite.

Consumer genetics is here, and it seems unlikely to disappear anytime soon. In fact, the next generation of consumer genetics products may very well be complete genomic sequencing, as promised by Complete Genomics, and even Illumina.

Although we may be decades away from it (or maybe only years), we will one day be confronted by some form of genetic identity theft. What does this mean, and how will this happen? Let me explain.

How can my genes be stolen?

My genes are unique to me, and there is essentially a 0% chance that anyone else in the world has the exact set of As Cs Gs and Ts as I do (with the exception of identical twins). How could someone possibly steal my genetic profile?

In the not so distant future, any cellular sample may be viable for complete DNA sequencing. For instance, after enjoying a nice lunch at the diner, leaving behind just one strand of hair may be enough for a stalker/mad scientist to determine your entire DNA sequence. They would have the entire blueprint of you.

What can be done with stolen genes?

Okay, so someone may steal and sequence my DNA, but what good does that do them?

Right now, nothing. They might learn that you carry a mutated version of the HFE gene and may potentially have a child afflicted with Hemochromatosis. Even worse, they could find out that there is a 70% chance that you are lactose intolerant!

In the future, the chimeric child of DNA sequencing, Stem Cell Research, Developmental Biology, and Cellular Reprogramming would allow for someone to derive stem cells from your one strand of hair. These stem cells might then be transformed into sperm or egg precursors, and  these cells would essentially allow anyone to have a child with you (without you). Think of the market for a service that advertises to prospective mothers: “Have a baby with Brad Pitt!” It’s actually kind of creepy.

It gets worse, and more obsessive. What if said “crazy Brad Pitt fan” decided that  having Brad Pitt’s child was not enough. No. She wanted more…she wants Brad Pitt for a child! Stealing Brad’s DNA, sequencing it, and reprogramming cells with his DNA would allow for the creation of a Brad Pitt embryo. An in vitro fertilization procedure later, and Brad Pitt’s ultimate fan can now also be his mother (to crazy fan: seriously, don’t do this…running a fan website is enough devotion).

Holy $h*t That’s Messed Up! How Can I Prevent This (esp. if I am Mr. Pitt)?

Truthfully, this is not something you have to worry about right now. The technology just is not there yet, although all methods necessary for something like this to happen are either developed or in development.

When we do reach the point where this is a real possibility, I cannot think of any way to stop someone who was committed enough to having your child (or you as their child). Maybe you can hire a personal assistant to walk around and make sure that all strands of hair, saliva and any other DNA containing materials are properly collected and destroyed.

Only with the extreme case of celebrities can I imagine there being a “black market” for stolen DNA, and even then, I doubt demand would be high enough to fuel such an industry. However, I will never say never when predicting the future in this field. To all celebrities out there: Let me know when you get that phone call, “So I’m your mother…sort of.” I give it 5-10 years.

So it’s official, I’m waiting for the Spit Kit to arrive. After some consideration, a group of us decided that 23andMe would be the best service to use to get our genes read (I’m careful not to use the words sequenced so as not to mislead people). I did it in a group of six and got the holiday discount, so it was actually less than $400.

I’ve spent some time at their site recently, and one of the more entertaining objects I have found is their human prehistory animation. Although the video is cute and likely does a good job of giving the non-biology person some bearings in the area, they should be careful with such a video. Some groups (Fundamentalist Christians for example) might view the video as the devil’s propaganda. I recommend taking a look, it’s funny AND educational.

23andMe Prehistory Animation

Nonetheless, I’m really excited to learn more about myself (and my family), despite the possibility of hearing some negative news (nothing I can do about my genetic make-up now…maybe in the future though, who knows). I’m going to be updating the status of my experience along with some advice I have on how to take the data further than the analysis that is given on the 23andMe website.

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You might be genetically inclined to get buzzed from drinking less. A study published on December 8th by researchers from the Earnest Gallo Clinic and Research Center indicates that the SNP rs1051730, is linked to a gene that affects how much alcohol you need to get buzzed.

The study is kind of funny. Participants were subjected to a “10 am 3 drink challenge,” and body sway was measured afterward. It was found that those homozygous for cytosine (C) at this particular locus responded quicker to the alcohol than did those homozygous for thymine (T). In fact, those who responded slower to alcohol (T individuals) were at a higher long-term risk to alcohol abuse.

What does this mean for me? For one thing, I could screen all of my dates in order to determine who would be the cheapest to take out drinking. More importantly, I could choose which combination to give my kid: do I prepare him to be the ultimate binge drinker in college by giving him two copies of the T gene? Or do I lower his risk for alcoholism by giving him two C’s, making him a lush? Such questions are going to plague me in my quest to build the perfect child.

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It’s been all over the news lately that companies are beginning to test peoples’ genes in order to determine whether or not they are predisposed to certain diseases or traits. Atlas Sports Genetics has recently offered a test to determine whether or not a child will be the next olympic gold medalist.

I’ll start by saying that genes do not determine everything. However, they can set limits or give advantages. In testing whether or not a child is athletic, Atlas Sports Genetics is actually testing to see what variation of the ACTN3 gene, which is involved in muscle contractions. One version of the gene has an association with sprint athletes, while the other version of the gene was not seen in these athletes. It is true, the test may prove to be quite telling for these children.

While I am supportive of using this information, I would never use Atlas Sports Genetics. The particular method of testing for this ACTN3 gene involves determining which single nucleotide polymorphism (SNP) your child has at position 66,084,671 of his or her 11th chromosome. Being that there are two copies of the gene, you are actually looking for two polymorphisms. The particular polymorphism is called rs1815739. A detail record of this SNP can be found on SNPedia (along with literally millions of other SNPs).

My problem with Atlas Sports Genetics is that they are charging $150 to test one SNP when you can pay $250 more at 23andMe to get 500,000 SNPs tested. That’s a half of a tenth of a penny more for each extra SNP. Instead of finding out whether or not you have a version of a gene that tenuously suggests you will be a better sprinter, you can also find out whether or not you are predisposed to autism, alzheimers, depression, or other such illnesses. The data from the 23andMe test is so powerful, you can even trace where and when your genes came from.

Even with a positive result from Atlas Sports Genetics, unless you keep your kid away from too much McDonald’s and on a steady diet of your dreams for the gold, he’s probably not going to the olympics. I wouldn’t say that it’s a bad test or a waste of time, but when the service is more cost efficient elsewhere, I can’t keep my mouth shut.

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