Monday, August 30, 2010

Accessible Research: What the heck is a microsatellite?

I've fallen off the face of the planet, with respect to my attempts at science blogging, and was jumped back into action today.

For our second installment, let's look at a paper recently published in Genome Biology and Evolution, found here:

What Is a Microsatellite: A Computational and Experimental Definition Based upon Repeat Mutational Behavior at A/T and GT/AC Repeats
Yogeshwar D. Kelkar1,2Noelle Strubczewski2,3Suzanne E. Hile2,3,Francesca Chiaromonte2,4Kristin A. Eckert*,2,3 andKateryna D. Makova*,1,2

This group of researchers aimed to identify what the defining factors of a microsatellite are (i.e when do we start to call something a microsatellite?). Wait a minute, what is a microsatellite? Where are they found? And, why do you care?

A microsatellite is a length of DNA found in your genome (not in the sky) with two important factors: 1. the "satellite" refers to a repeating unit - think of a string of identical beads; and 2. the "micro" part, referring to very short lengths of DNA - think very tiny beads. There are four DNA bases, A, T, G, and C, that can be arranged into these beads. So, so if each "bead" were made of a short stretch of DNA, say, "ACC", then the 6-repeat long microsatellite would be:

 1  2  3  4  5  6 

So what, right? Why do you care about repeats in your DNA? Well, you should care because changes (mutations) in these microsatellites have been, "associated with numerous neurological diseases". One you may have heard of is Huntington's disease, which gets progressively worse and debilitating over a person's lifetime. You can read more about it here

That reminds to me mention something unique about these microsatellites, compared to the rest of our DNA, they mutate very rapidly. This is thought to be because the replication machinery slips and forgets where it was in the repeat, either jumping a step ahead, or back-stepping to effectively increase or decrease the length of the microsatellite.  The replication machinery is always in action because our cells are always being regenerated - think of your hair growing, your skin healing over a wound - all of these things take new cells, and new cells require the DNA to be replicated using this machinery.

But, until recently it wasn't clear when a set of repeats starts to acquire this fast mutation rate, definitive of microsatellites. Do there need to be 3 repeats? 4 repeats? 10 repeats? This can make a big difference to diagnosing a disease related to microsatellites. If 3 repeats are not dangerous, but 4 repeats are, clinicians who can identify 3 repeats may have a head start of preparing their patients for potential treatments, and advise on the potential heritable effects (if the patient is considering having children).

Together the scientists above have combined laboratory experiments with computational predictions to determine that the threshold for a length of DNA to acquire the properties of being a microsatellite (namely the very fast mutation rate) is not a hard-and-fast number, but that it varies, depending on the DNA composing the repeats (beads), and the machinery used during replication. 

This means that, if we know what the DNA code is, and how it is being replicated, we can figure out whether a particular microsatellite has reached the threshold of being "dangerous" or if it is, so to speak, still "benign". 

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