Belinda Ghillino asked:
Can chromosomes be repaired? My daughter has Angelman Syndrome, and I was very excited to hear that there might be "tools" to repair this.
We put this question to geneticist and Naked Scientist, Kat Arney...
Kat - Angelman syndrome is a really fascinating genetic disorder. I mean obviously if you're a family thatís affected by it itís probably more distressing than fascinating.
But itís something called an imprinted disorder. So normally, we get one set of all our genes from mum, one set of genes from dad, and they're both pretty much the same. Both copies of the genes are working; the genes that make your hair, your eye colour, all this kind of thing. Both copies, mum and dadís copies, are both working. With certain genes, there are about 100 genes in humans, itís either mum or dadís version that works depending on the gene, and the other one is always switched off. And itís always very stereotypical. At certain genes for example, there's a particular growth factor and that is always dadís version that is on in your cells. Particularly, these genes seem to be relevant in development in very early life.
Angelman syndrome is a disorder where this process has gone wrong. Basically, the copy thatís meant to be on is not working and there's no backup, whereas if you have two copies of every gene youíve got a backup. So, there's been a lot of discussion with some of the new genetic technologies that are coming online, these things called gene editing techniques. There's a very famous one called CRISPR, which listeners might have heard of, where you can actually directly tinker with the chromosomes - you can change bits in the DNA.
The problem with something like Angelman syndrome is that itís a developmental disorder. Itís something that really starts from when the baby is growing in the womb and continues on into life. Itís going to be very hard, even if you could repair the DNA. Itís debatable as to whether you could actually repair or turn back the clock and turn back the problems that itís caused with the growing child.
Chris - So, you're saying there are two problems. One is that youíve not just got to deal with what is causing this disorder but then youíve got to contend with the fact that youíve got an accrued problem already under your belt.
Kat - Exactly. So, if you have say, a genetic problem that means you donít make insulin or an enzyme in your pancreas, or an enzyme in your body or your stomach or something like that, maybe you could change the DNA in just those cells and you would start making the enzyme again, and you would be well. But for a lot of the developmental disorders where theyíve started almost from the fertilised egg and through development, those kinds of things are going to be hard to reverse.
Although there are some intriguing examples we probably donít have time to talk about where there may be things that could help. But I think that gene editing for developmental disorders and those big chromosome disorders is going to be tough.
So in such cases, it would appear necessary to do the gene repair before, at, or shortly after fertilization in order for the therapy to take effect. Atomic-S, Sat, 25th Apr 2015
That's right; this is the concept of pre-implantation genetic diagnosis and repair. Intervention at the early-embryo stage would make it easy to correct all of the cells so that their developmental fates were normal; otherwise there might be developmental consequences of the abnormality that would not be reversible later, even with gene correction at that stage. For instance, if a gene caused a malformation, putting the gene right after the body had mal-formed would be like slamming the stable door after the horse has bolted. chris, Sat, 25th Apr 2015