Leaky genes
I just read something incredibly exciting that I want to share with you. The reference can be found at: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=379123&action=stream&blobtype=pdf
While geneticists know that genes can be imprinted and turned off, they don't know why it happens. Dr. Beaudet and Dr. Jiang out of Baylor suggest that the purpose of imprinting is to allow a greater range of expression of certain traits. This would allow many more differences between individuals. Imagine all of the different shades of gray versus just black and white and a single gray.
So, a healthy normal person has these imprinted genes because it allows the species to demonstrate a wider range of traits. So, if something horrible were to happen and different traits are necessary to survive, then there would be some people in the species who would be able to survive.
You know how we have been told that maternal genes have been silenced and that in the absence of the paternal genes, the PWS child must do without? Well, that may not be true. Evidently the maternal genes are not truly silenced but are often leaky.
More importantly, there is a genetic theory (unproven) that suggests that these genes may be turned on again (at least partially) in response to environment. The rheostat model suggests that a silenced gene can become activated, possibly even within the lifetime of a single individual.
If this is the case, it should be possible to "cure" PWS children by providing them with environmental stimulation that would turn on these silenced genes (at least partially). I would suggest that the necessary stimulation would resemble the physical therapy and occupational therapy and movement and talking and sensory stimulation that we are providing our children from a very young age.
This may be one explanation for the impressive outcomes that are being seen in this new generation of PWS kids.
So, as I understand it, it would apply to those genes that are turned off. A UPD child would have two sets (2X maternal) of "turned off" genes and a deletion child would have one set of "turned off" genes (1x maternal).
A UPD chile would theoretically have twice as much material to work from. If they got 20% read through/leakiness on each of their turned off genes (2x maternal) they would get a total of 40%, whereas a deletion child would be forced to pull the full 40% from the single turned off gene. So, in that way a UPD child would have an advantage. The UPD child would also have the advantage in that they have the correct amount of all of the genes that have not been silenced, where as a deletion child has the daddy's contribution deleted and must make due with what the mama contributed.
The disadvantage for a UPD child is that they have other genes (those that are not turned off) that are duplicated and they are getting a double dose of some genes that they were meant to get a single dose of. Those double doses may be somewhat harmful although, you could hypothesize that the same mechanism could work in reverse and these genes could be dialed back.
As for the cure. My boy is PWS by deletion and I think more about that than I do UPD. As I see it, nothing can bring back the genetic material he has lost. So, then, why don't we give up? We don't give up because we are banking on the fact that the human genome, brain, and body is incredibly redundant and is capable of adapting and responding to external stimuli.
How can the body adapt? One way is to compensate with other parts. PWS kids have low tone and so they have to develop greater strength to compensate for teh tone. PWS kids have more hunger and so they have to develop greater willpower to compensate for the hunger.
The rheostat theory provides another way of looking at it. Instead of just compensating for teh problem with other parts of the body, we may be actually turning the quiet gene back on. We may be teaching the body that it actually needs that gene in teh current environment and therefore teh gene should not be silenced. How much could the gene be dialed up? It isn't known. The paper I cited came out in 2002, and so it is a relatively new idea in genetics. But, remember, the idea of gene silencing is also relatively new and certainly you could argue that it is not well understood.
Dr. Beaudet, in his paper, makes the argument that many of these silenced genes can be described as regulating growth and behavior. He goes on to hypothesize that growth and behavior are the two things that an organism must be able to most quickly modify to adapt to a changing environment and survive. Therefore the silencing and dialing up and down of these genes allows a theoretically wider ranger of behavior and better adaptability should the environment dramatically change. Otherwise, why silence one gene (either the maternal or paternal)? Why not let both work and let the body deal with excess genetic product. After all, most genes are able to be regulated without having their partner silenced...
Long answer, but I think yes, a cure. Although, to be fair, cure is too strong of a word. Perhaps it is better to say that through environmental intervention we may be able to normalize our children's genetic material!
Also see TMG/Methylation
Also see http://www.geneimprint.com.
