Highly read on www.cell.com 23 Dec–22 Jan

Genetic mutations occur at random, but where in the genome they occur is non-random. Jonathan Sebat at the University of California, San Diego, Jun Wang at BGI-Shenzhen in China and their group report that some regions of the genome mutate a 100 times more frequently than others, and that genes linked to autism have higher than average mutation rates.

To track emerging mutations, the researchers sequenced the complete genomes of ten sets of identical twins with autism spectrum disorder and their parents. The analysis revealed 'hotspots' where new mutations tend to cluster and showed that mutation rates were associated with certain DNA sequences or with specific aspects of how the DNA is packaged. Disease genes — including those implicated in autism — showed high mutation rates, as did those expressed in the brain.

Further study of mutation hotspots could help researchers to identify more genetic risk variants, and to better understand human variability and genome evolution.

Cell 151, 1431–1442 (2012)