Dr. Janine LaSalle covers the epigenetics involved in autism-spectrum disorders. 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.
Epigenetics in Autism-Spectrum Disorders
I’ll start with saying I kind of joked that I’ve been in epigenetics before it got trendy, so I came from being in the imprinting x-inactivation field, so I got interested in imprinting back in the early ‘90s. At the time it was that quirky exception that geneticists could say, “Okay, that only applies to imprinting and x-inactivation. But I think what’s exciting about epigenetics now is that it’s impacting everything – everywhere. So I think the rest of the community is starting to appreciate that the whole genome has affected epigenetics at some level, and that genes can be impacted by environmental factors, and that could have long-lasting effects through epigenetics.
So it’s exciting for me to see this field blossom from being, again, sort of quirky exceptions to weirdos like me that wanted to work on it, to something that is really relevant to understanding disease processes. I think, you know, understanding the human genome has been great for knowing the basic code, but clearly there’s a lot more complexity on top of that, and that’s where epigenetics comes in.
I also think it’s great that epigenetics can really bridge so many different disciplines, and that’s where my research is starting to go now is I’m kind of like a kid in a candy shop of saying all these collaborations with epidemiologists, toxicologists, people in nutrition, understanding how genes can interact with these fields through epigenetics.
So we’re very interested in human neurodevelopmental disorders, and definitely ones on the autism spectrum, and we’d love to get at the big puzzle of autism, but it is a big complex question. So the strategy in my lab has been taking for really the past decade is to use genetic disorders that affect epigenetic pathways where you know the gene that causes it, and to use that towards trying to understand the big confusing question of autism.
So, for instance, Retts Syndrome is one where when the gene for that was found in 1999, and I just jumped on it because this is the gene is MECP2, which encodes a protein that binds to methylated DNA, so it’s definitely an epigenetic reader in the brain. And it was just fascinating how this human disorder could have this mutation in this gene that we thought we knew what was going on before, and it’s still a really interesting question to follow that.
Also the imprinting regions, like chromosome 15q113, which has the imprinted disorders of Angelman and Prader-Willi, now also it’s showing up in a lot of copying and variation, so autism is one of the most common copy number variation, also for schizophrenia and epilepsy. So it keeps coming up again, and again. So there’s something about these imprinted regions, especially in the developing brain that’s particularly interesting.
So we’re really trying to understand mechanisms of these known pathways, and then using that to try to figure out: Can we then generate hypothesis for what may be going on with autism?
“…understanding the human genome has been great for knowing the basic code, but clearly there’s a lot more complexity on top of that, and that’s where epigenetics comes in.”
So eventually what I’d like to get from these is not only understanding the complexity of the epigenetic mechanisms, but using that to help potentially diagnosis of autism, also maybe finding genes, if we know the genes that are epigenetically regulated. I guess the hope with epigenetics is it could be reversible. So, you know, if you have a genetic mutation it’s kind of hard to fix that, but if it’s an epigenetic change, you could potentially find a drugable target through epigenetics.
Well, I mean, I think prevention is a big thing that we can also think about. So, I mean, obviously most of, I think, U.S. medicine is geared towards treatment and coming up with a drug to treat something, but one of the epidemiology studies that I wasn’t involved in but I collaborate with them at the MIND Institute, so actually Rebecca Schmidt, who’s here, and Irva Hertz-Picciotto, are showing that folate is protective for autism in the same way that it is for neural tube defects, and that’s exciting from the epigenetic perspective because this is methyldonors that contribute to DNA methylation.
It was striking to me when I kind of saw this data, it’s like, wow, if, you know, it turns out I think 30 percent of women were taking prenatal vitamins pre-conception, and if you could just even double that by sort of a public health message of prevention, you know, it could be preventing more autism cases in the future.
So, I mean, I think that’s the nice interface, too, is that not only could we – there’s sort of a long pipeline for developing medicines, but prevention is something you can do for the next generation of pregnancies, and hopefully help.