The Unsilencing of a Gene

As many of you know, I love genetics. So when I was perusing Nature on my iPad this morning (working on my New Year's resolution), I went straight for the article with the word "allele" in the title. (An allele is a version of a gene; we all inherit two alleles of each gene -- one from our mother and one from our father. This concept is very important for the article I read.)

The article was about a drug that was found to "unsilence" an allele in mice, serving as treatment for a disease called Angelman syndrome, a severe neurodevelopmental disorder. 

Normally, we have two potentially active alleles of each gene. However, in a particular gene called Ube3a, only the maternal allele "works" due to a process called imprinting. The paternal allele is effectively silenced. So if the maternal gene is mutated or dysfunctional in some way, then the gene product of Ube3a doesn't get made -- there is no functional paternal allele to take over. The result is Angelman syndrome, according to this article. 

So researchers looked at 2,306 different molecules (yes, that number is right) to see whether any of them would "unsilence" the paternal allele. One -- an anticancer drug called a topoisomerase inhibitor -- did. The scientists eventually found another topoisomerase inhibitor that worked even better, and tested it in vitro (in culture) and in vivo (in living mice). In both cases, the Ube3a gene was activated in the target neurons. 

While this type of treatment has a long way to go before it is approved for use in humans, this research study does offer hope to some people. (Angelman syndrome is estimated to affect 1 in 15,000 births, according to the Nature article.) 

This article also contains many concepts that I learned in my genetics course. Which made it easier to understand, of course, and also reminded me that what we learned was significant and will be important in my future as a physician-scientist.

Background: image of a rat neuron.

A Good-Natured Resolution

I'm not much for making New Year's resolutions. They seem to stick for about a month, and then ... not so much. But this year, I decided to try what so many millions of people do and make my own resolution, one that hopefully I can (and will want to) keep. There is some additional incentive, other than just meeting a goal -- I invested money in this resolution up front, so I'm betting on that keeping me motivated. 

So what do I want to do? It's not your typical resolution. My goal is to read Nature every week. (Well, not ALL of it, but a good bit of it.) For those of you unfamiliar with this magazine, it's a weekly publication, and is one of the premier scientific journals in the world. Because of its prestige, its articles are only available to its paid subscribers. Countless times I have stumbled across a Nature article on PubMed and salivated over the abstract ... but I had to move on, because there was no way for me to read it. 

Thanks to some Christmas money from my grandma, problem solved! I subscribed the day after Christmas, and will be getting both the print edition, as well as online access going back more than a dozen years. (And of course, there is a Nature app for the iPad!) A subscription -- even a student subscription, which is half the regular subscription price -- cost a pretty penny ($99 students / $199 everyone else). But I think it will be worth it. After all, how can any self-respecting MD/PhD-wannabe NOT be subscribed to Nature? My point exactly. 

Assuming that I do follow through with this "resolution," I hope to post here about some of the things I read. There are very technical articles, of course, but also editorials, features, and other types of material in the magazine. I look forward to my year of Nature, and to writing about what I learn.

And as you may have noticed, I have made a new "discovery" related to blogging, as well. With the iPad blogging app I have (BE Write HD), you can set backgrounds for your blog posts. It took a bit of researching as far as how to reduce an image's opacity so that it would work as a background (I downloaded a photo editor app, PhotoForge2, for that). But I've got it figured out now.

And so here you have in the background a cell -- soon to become two cells -- in anaphase of mitosis. Pretty cool, eh?

Gene-ious!

Geneticists, and scientists in general, may not exactly have a reputation as having a sense of humor. But, I argue, many of them truly do. I have evidence to prove it, which I will present in this post. I stumbled across this evidence when searching for an appropriate name for my iPad. I simply Googled "funny gene names," and came up with a list of sometimes hilarious, sometimes poignant, sometimes culturally referenced, names for genes of various organisms (especially my dear Drosophila melanogaster). Here are some of my favorites, taken from a couple of Web sites that I found: jpetrie.myweb.uga.edu/genes.html, www.curioustaxonomy.net/gene/fly.html, and tinman.nikunnakki.info/browser. I hope they bring a smile to your face, as they did to mine.

These are all from Drosophila melanogaster:

Gene name	History behind name
18wheeler	This gene is expressed in 18 stripes in developing larvae.
agnostic	Agnostic flies fail to learn odors in certain temperatures. Agnostic people also have problems making up their minds.
amontillado	Mutant larvae do not hatch. In Edgar Allen Poe's short story "The Cask of Amontillado," a man who is still alive is walled in.
brokenheart	A mutation in this gene causes a defect in heart development.
cheap date	These mutants are very sensitive to alcohol.
cleopatra	In these mutants, an interaction with the asp gene is lethal. Queen Cleopatra supposedly committed suicide with a poisonous asp.
clown	Mutants' eyes are red and white.
coitus interruptus	Mutant males literally engage in withdrawal during copulation (it lasts about 60% of the normal 20 minutes).
dachshund	Flies have crippled legs, resembling this dog species.
dreadlocks	The connections between nerve cells of these flies are not correct, and the result resembles the hairstyle of the same name.
drop dead	These mutants' brains deteriorate rapidly; they begin to walk in an uncoordinated way and then die.
dunce	These flies have impaired learning.
glass-bottom boat	These flies' larvae are transparent.
grim, reaper	These two genes together mediate programmed cell death (apoptosis) in the fruit fly.
groucho	Mutants have a greater-than-normal number of bristles (like Groucho Marx).
icebox	Female icebox mutants do not care about courting males.
ken and barbie	Both male and female mutants lack external genitalia (like Ken and Barbie).
limo	This gene is involved in protein transport.
lot	A Biblical reference: mutants like salt more than usual.
lush	Mutation causes increased desire for alcohol.
out cold	Mutants lose coordination when the temperature falls, and eventually become paralyzed.
sarah	Mutants are practically sterile (another Biblical reference, to Sarah, Abraham's wife).
stuck	Mutant flies get stuck in females.
swiss cheese	Mutants have holes in their brains that resemble swiss cheese.
van gogh	Swirling wing hair patterns resemble van Gogh's paintings.
yuri	Mutants have difficulty with gravity. The gene was found on the 40th anniversary of Yuri Gagarin's historic space flight.

Thanks to the tinman Web site I referenced above for these gene names and explanations; visit the site for more. Fun stuff!