There is an interesting new paper out in Genome Research from Eric Lai’s lab (Miura et al. 2013) that finds many genes have much longer 3’UTRs than previously annotated. Sometimes these extended 3’UTRs look constitutive, other-times they have found alternative gene isoforms with 3’UTRs that terminate transcription (on average) several kb further downstream.
In some ways this isn’t too surprising, having spent a lot of time these past years gazing at the UCSC genome browser, it is clear that 3’UTRs keep getting longer and longer. For those in the lncRNA field, this presents some difficulties in determining whether an RNA downstream from a 3’UTR in the sense direction is an independent transcript with it’s own start site, a processed RNA from the 3’UTR, or part of the UTR but for some reason transcription joining the two hasn’t been found. Generally transcripts downstream from a 3’UTR that pass whatever cuttoffs a study imposes will look like (and be called) long noncoding RNAs (lncRNAs). Continue reading
So the ENCODE consortium, which aims to catalogue all the functional elements in the human genome, have just published their results to-date in 30 articles in Nature, Genome Research and Genome biology. As far as I can tell all the papers are open access so anyone can read them. A reasonably useful place to start is Nature’s ENCODE explorer.
To date I have only read a few of the new ENCODE papers (and no doubt will be busy reading more over the next week or two) but here are some of my initial thoughts.
1. As far as biology goes, the new ENCODE results don’t provide a lot of big novel insights. Many of the conclusions in ENCODE 2012 are the same as those from the ENCODE pilot paper in 2007, except now they are over all the genome, not just 1%. Continue reading
After reading Mike Snyder’s recent (and very cool) mega-omics-on-self paper, it dawned on me that I am not the only Mike Clark working in genomics. As I’m sure my scientific (but more beardy) doppelganger can no doubt vouch, this happens all the time when you have a common name (there were, I believe, three Mike Clarks at my high school).
The Stanford Mike “Geneticist extraordinaire” Clark also does some science-based blogging and earlier this year outlined why he is going to get his exome sequenced. It’s a persuasive piece which I encourage everyone to read, although for many people the actual outcome to the question “should I have my genome sequenced?” may be more determined by legal and insurance implications, than whether or not they would like to know their genetic code. In my opinion, Standford Mike’s first reason of curiosity (both from a personal and scientific point of view) is reason enough, but I also think the potential medical benefits of knowing your genome are going to become progressively larger. As Standford Mike says:
“Moreover, as more and more information regarding the genetic causes of various traits and diseases are discovered, my exome sequence will always be at hand for me to cross-reference. Imagine that tomorrow a study is released identifying a gene that tells you with complete confidence whether or not you’ll get type 2 diabetes. I would check that gene in my own exome for mutations immediately!
That may sound unrealistic, but when it comes to conditions like cancer, these kinds of studies come out all the time. I may identify a random mutation in a gene that pre-disposes people to getting a particular type of cancer in my own genome, and then I will know that I need to have my doctor monitor for that. Having worked closely on brain cancer for a few years, it struck me that the reason it’s the deadliest type of cancer is because by the time we detect it, it’s already at a very advanced stage. But if we have a gene or set of genes that we know predisposes people to get malignant brain tumors, we could look in our own exomes for mutations in those genes and then get ourselves MRIs starting at a particular age to try to detect them earlier and hopefully allow effective, long-term treatment.”
Something quite similar to this came out of the Mike Synder mega-omics-on-self data, where they predicted an increased risk of diabetes based on his genome and then during the course of the study observed the onset of diabetes. Blood glucose tests are cheap and type-2 diabetes is reversible with lifestyle changes (as Mike found) so this was a clear example of the benefit of monitoring yourself for diseases you have a predisposition to.
Myself and some other members of the Mattick Lab caught up with Mike Synder at HGM earlier this year, unsurprisingly the subject of sequencing your own genome/exsome was the main topic of conservation. While chatting about a particular phenotype I have but which is not found elsewhere in my family Mike suggested I should get my genome sequenced, something which is quite tempting. So what does everyone else think, do you want your genome sequenced?
As you may have heard, Eduard Khil AKA Mr Trololol died a few days ago. Thanks to Martino, the Mattick lab will always have his music
etched burned into our neurons. The lab just doesn’t sound the same without hearing his vocalizations emanating from the office one, two or perhaps three times a day. So thanks for the memories Eduard, rest in peace.
The extent of the genome that is transcribed (known as pervasive transcription) and the amount of “dark matter” RNA (uncharacterised and/or function unknown transcripts) produced by the cell has ignited a few controversies over the years.
This month marks 2 years since the last salvo from the pervasive transcription ‘skeptics’, van Bakel et al, 2010, was published in PLoS biology. van Bakel claimed, amongst other things, that previous studies had overestimated the pervasiveness of transcription due to false positives, that the small percentage of RNA “dark matter” in their RNA sequencing datasets supported this conclusion and that much of the low level transcription found in intergenic regions were probably transcriptional bi-products (ie: some sort of noise, be it technical and biological).
We were critical of many aspects of this study in a reply we published in PLoS in 2011 (further info here). Now that another year has past it’s probably worth seeing how their conclusions are holding up. Continue reading
Some praise for Dr Mercer’s work on the blogosphere (Dr. Mary Mangan @ Open Helix Blog). Video Tip of the Week: Mitochondrial transcriptome GBrowser
Perhaps something like Chromozoom might make it easier to visualize transcriptomic data for smaller genomes. Did I just criticize our own work? SNAP!
Oh, get a grip is long or large? Why don’t I strap on my large RNA helmet and squeeze down into a long noncoding RNA and fire off into noncodarnia, where large RNAs grow on long RNAs….. arghh
Oh, get a job? Just get a job? Why don’t I strap on my job helmet and squeeze down into a job cannon and fire off into job land, where jobs grow on little jobbies