Dr. Gudrun Moore discusses her studies of key genes involved with fetal growth and their regulation. This short take was shot during a break at Keystone Symposia’s meeting on Environmental Epigenomics and Disease Susceptibility held in March 2011 in Asheville, North Carolina.
Imprinted Genes and Fetal Growth
As I am fundamentally interested in looking at very small babies and why and which genes are involved in the absence of growth in ____ around growth restriction. So we have been over the last 15 years really looking at imprinted genes, which of course, have a huge epigenetic profile because the majority of the control of the imprinted genes is through epigenetics.
And we’re looking at these genes particularly in terms of how they affect growth in utero, so we’ve been collecting big cohorts of placenta samples with maternal and paternal DNA because to look at epigenetics, you have to have DNA really from both parents, and then we’re analyzing the expression of these imprinted genes and seeing how they correlate with medical premises, such as birth weight, head circumference and other factors such as the maternal weight and the paternal weight.
We’re particularly interested in which genes are involved in growth, and there’s going to be thousands, so the imprinted genes in the mouse appear to be very closely linked with growth, so we’re looking at the orthologous genes in the human is a good handle on looking at specific genes, particularly those that are going to be epigenetically regulated. And of course, I think that growth will have quite a large epigenetic part to it, so this is a really good handle for that, so those are the questions we’re looking at.
“…we start to understand how we can actually help those individuals with these disorders through epigenetic therapeutics, which I think will definitely happen, maybe in the next five to ten years.”
Well, it really depends how important epigenetics is, and I guess that’s what we’re establishing across the whole field at the moment. I’m particularly interested in looking in the human to see how important it is in humans. It’s very clearly it’s fairly important in the mouse. The human is a bit more sophisticated in its behavior, I think, and some of the genes that are imprinted in the mouse are not imprinted in the human or some of the epigenetic events that happen in mouse models are not happening in the human, but it may be that in the human particularly I think growth will be a big issue, big medical issue, but I think that behavior and brain development is going to be very important epigenetically in the human, and of course, mental retardation and associating neurological problems are huge in man and pose a huge healthcare burden.
So if a large part of this is epigenetic, and we start to understand how we can actually help those individuals with these disorders through epigenetic therapeutics, which I think will definitely happen, maybe in the next five to ten years, then I think that’ll be how epigenetics helps in medicine in man.
We have been quite fortunate in research we’ve done recently that’s sort of flagged up one imprinted gene that appears to be potentially a biomarker for growth. And we’re looking in maternal blood, where the lady is pregnant, to see whether we can use this marker as an indicator of growth. So we would look up moms that are pregnant who have normal birth size babies and compare them with moms who are pregnant that end up having growth restricted babies and see whether this marker is different in their bloods. And it could then be used down the line as a marker for growth. Whether it will happen that way, I don’t know, but I think that this sort of approach is going to be used by others for other diseases not just growth for cancers and possibly neurological disorders, but careful experimentation needs to be done within the same families for the same disease phenotypes, and that’s more challenging in man.