Wiring the Brain

Source Why are some brain disorders so common? Schizophrenia, autism and epilepsy each affect about 1% of the world’s population, over their lifetimes. Why are the specific phenotypes associated with those conditions so frequent? More generally, why do particular phenotypes exist at all? What constrains or determines the types of phenotypes we observe, out of all the variations we could conceive of? Why does a system like the brain fail in particular ways when the genetic program is messed with? Here, I consider how the difference between “concrete” and “emergent” properties of the brain may provide an explanation, or at least a useful conceptual framework There is now compelling evidence that disorders like epilepsy, schizophrenia and autism can be caused by mutations in any of a very large number of different genes (sometimes singly, sometimes in combinations). This is fundamentally changing the way we think about these disorders. It is no longer tenable...

This post first appeared as part of a SpotOn NYC special event on Communication and the Brain (March 2013), on nature.com.   When I started the Wiring the Brain blog a few years ago, it was with the intention of writing mainly for students, scientists and clinicians in the fields of genetics and neuroscience. Many of the posts deal with advances in our scientific understanding of the causes of neurodevelopmental and psychiatric disorders. Perhaps because of that, or just due to general interest in the broader themes, the blog has also become widely read by non-specialists. This presents some exciting opportunities to write in a different way and to convey the excitement of the field of neurogenetics to the general public, but also raises some particular challenges. The biggest difference I have found is that the assumption of a shared, global perspective is not always valid. When writing for scientific colleagues there is an implicit expectation of a c...

In Part 1 of this blog, I considered the various definitions of the term epigenetics and the confusion that can arise when they are conflated. Molecular epigenetic mechanisms modify chromatin structure and provide a means to stabilize a particular profile of gene expression. They also allow that profile to be passed on to a cell’s descendants, through mitosis . For this reason, epigenetic profiles have been called “heritable” (meaning through cell division). It is easy to see how that definition can be extrapolated to the idea that epigenetics could provide a means of heredity from one generation to the next. This idea has attracted substantial interest, with many people seeming to think it overturns classical genetics (the inheritance of characters based on DNA sequence), and rehabilitates Lamarckian evolution by supplying a respectable molecular mechanism. This view has gained particular prominence of late in the study of behaviour and psychiatry, with th...

“You keep using that word. I do not think it means what you think it means”. The insightful Inigo Montoya. Epigenetics is a word that seems to have caught the public imagination. This is especially true among those, both in science and without, who decry what they see as genetic determinism or at least an overly “genocentric” point of view. Our genes are not our fate, because epigenetics! Such-and-such disorder is not really genetic, because epigenetics! Acquired characteristics can be inherited, because epigenetics! The trouble with epigenetics is that the word means very different things in different contexts. Each of them may be quite valid, but when these meanings are conflated or when the intended meaning is not specified, the word becomes dangerously ambiguous. This is especially evident in the fields of behavioural and psychiatric research where the term is much abused, often, it seems to me, to give an air of mechanistic truthiness to ideas that a...

This is a modified version of a letter published in Trends in Genetics: Kevin J. Mitchell (2012). Genetic entropy and the human intellect. Trends in Genetics, 14 th December 2012. Two articles by Gerald Crabtree float the notion that we, as a species, are gradually declining in average intellect, due to the accumulation of mutations that deleteriously affect brain development or function [ 1 , 2 ] . The observations that prompted this view seem to be: (i) intellectual disability can be caused by mutations in any one of a very large number of genes, and: (ii) de novo mutations arise at a low but steady rate in every new egg or sperm. He further proposes that: (iii) genes involved in brain development or function are especially vulnerable to the effects of such mutations. Considered in isolation, these could reasonably lead to the conclusion that mutations reducing intelligence must be constantly accumulating in the human gene pool. Thankfully, these f...