The initial conditions that disrupted neural development are difficult to identify after autism has been diagnosed, but hints might be found in the patterns of gene expression that those conditions leave behind. Kunkel and his team plan to compare the expression profiles in blood samples from families affected by autism with those from healthy controls, searching for differences that might indicate a gene expression 'signature' for the disorder; many genes expressed in the brain are also expressed in blood cells. Patterns of gene expression do not always reflect the final protein composition, however, in part because primary transcripts can be alternatively spliced into several, distinct messenger RNA (mRNA) sequences called isoforms. Kunkel and colleagues propose that atypical patterns of mRNA isoforms expressed in neurons may lead to the abnormal brain development seen in autistic brains. To search for these patterns, they plan to analyze patterns of mRNA isoforms in blood and autopsy brain samples from people with the disorder, focusing on the transcripts expressed in late neuronal development, around the time of autism onset. These studies may lead to a simple test for diagnosing the disorder and may implicate new cellular pathways in autism, opening up new avenues for research.