Scientists like to warn you not to talk about “the gene for” a particular disease or trait.
But such scalding is not always very effective. We like simple explanations, so we like to find simple connections between genes and phenotypes.
Which is why a new paper is important. The authors, a large Turkish-American collaboration, found that mutations in a gene, WDR62, are associated with severe brain malformations in 9 patients. But what’s interesting is that it doesn’t cause any particular malformation.
If you have two faulty copies of this gene, your brain won’t be normal, but what goes wrong varies widely amongst different people. Although the 9 cases had some features in common, such as microcephaly (small head and brain), in other respects they differed greatly.
As the authors put it, mutations in WDR62 cause
a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients… had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities.
These are distinct entities, in the sense that you can have any one of them, without having the others. And they are different brain changes. What the authors mean is that everyone assumed that, because they’re different, they must have different genetic causes. They’ve just shown that this is wrong.
So what is WDR62 “for”? Experiments in mice showed it to be involved in the migration of new neurons from their origin to their final location in the brain. So it’s “for” correct neuronal placement, although how it works remains unclear.
WDR62 ought to remind us that there’s a long and winding road from gene to phenotype, and that the same gene can, when mutated, cause very different symptoms. This is especially interesting in the light of recent evidence showing that the same mutations can cause a range of behavioural disorders from autism to ADHD to schizophrenia.
Bilgüvar K, et al (2010). Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature, 467 (7312), 207-10 PMID: 20729831