Showing posts from February, 2012

Nerves of a feather, wire together

Finding your soulmate, for a neuron, is a daunting task. With so many opportunities for casual hook-ups, how do you know when you find “the one”?

In the early 1960’s Roger Sperry proposed his famous “chemoaffinity theory” to explain how neural connectivity arises. This was based on observations of remarkable specificity in the projections of nerves regenerating from the eye of frogs to their targets in the brain. His first version of this theory proposed that each neuron found its target by expression of matching labels on their respective surfaces. He quickly realised, however, that with ~200,000 neurons in the retina, the genome was not large enough to encode separate connectivity molecules for each one. This led him to the insight that a regular array of connections of one field of neurons (like the retina) across a target field (the optic tectum in this case) could be readily achieved by gradients of only one or a few molecules.

The molecules in question, Ephrins and Eph rec…

I’ve got your missing heritability right here…

A debate is raging in human genetics these days as to why the massive genome-wide association studies (GWAS) that have been carried out for every trait and disorder imaginable over the last several years have not explained more of the underlying heritability. This is especially true for many of the so-called complex disorders that have been investigated, where results have been far less than hoped for. A good deal of effort has gone into quantifying exactly how much of the genetic variance has been “explained” and how much remains “missing”.

The problem with this question is that it limits the search space for the solution. It forces our thinking further and further along a certain path, when what we really need is to draw back and question the assumptions on which the whole approach is founded. Rather than asking what is the right answer to this question, we should be asking: what is the right question?

The idea of performing genome-wide association studies for complex disorders…