Professor Judith Rapoport describes gene expression as messy and inconsistent, which is explicit from a recent schizophrenia study.
Well I don’t know if you want to go there, because among geneticists now that are very excited with knock-in knock-down, various sort of functional measures, gene expression is considered very messy, and so it’s very hard to know what’s going on in gene expression.
We compared a whole genome expression scan of our schizophrenic patients with their healthy siblings, which means they were totally well-matched for ethnicity of background, and so on, and there were 1500 genes that were either substantially higher or lower – 1500. That’s one problem.
So, that’s with white cells, but still highly significant. We also looked at the gene expression – we have a whole bunch of patients with a part of the chromosome missing called VCFS or 22Q11, it’s called, the Velocardiofacial Syndrome or DiGeorge Syndrome, and four of our schizophrenic patients had that. And that’s a big hint for schizophrenia, because people with this deletion have 26 times the rate of schizophrenia as normal. Schizophrenia is one percent of the population, and if you have an identical twin with schizophrenia, your rate of having it is 50 percent. That is the biggest risk factor known, but the VCFS deletion on chromosome 22 is a twenty-six-fold risk, the highest risk known. So we looked at the gene expression for those patients and controls, and we found two things, one we expected that you only have half the expression in that rate because you only have one copy of the gene, and so the gene expression was low for those patients. But we also found that, outside of that region, there were genes on other chromosomes that are way high and way low, which means that there are regulatory elements that were either suppressing or increasing genes all over the genome.
So gene expression is so complicated for all those reasons, to say nothing of the fact that different parts of the brain express genes differently. And what’s more, at different ages, studies with rats show there are all sorts of genes that are only turned on at certain times during development, and they can go on at a certain age, go off, and then go on again at aging. So, although expression is interesting, its immediate application for finding out the things we want to know – it looks way below things like copy number, variance, or sequencing. I think most geneticists would agree with me on that.