Human genetics: Fruits of exome sequencing for autism

http://www.nature.com/nrg/journal/v13/n6/full/nrg3248.html?WT.ec_id=NRG-201206

A role for de novo mutations in ASD has been suggested by previous studies of copy number variation and smaller-scale exome sequencing studies. In the recent studies, Iossifov et al. sequenced 343 family 'quads' (the parents of a single child on the autism spectrum and its unaffected sibling), and Sanders et al. also included 200 quads in the 238 families they sequenced. O'Roak et al. selected 189 trios (a child with ASD and its parents), and Neale et al. also sequenced 175 trios. Although the details differ among the four studies, the findings reveal several shared patterns and interesting leads.

Each of the studies identified de novo mutations that are predicted to disrupt gene function in some of the affected children: the total haul is 127 gene-disrupting mutations. Although only a proportion of these would be expected to be causal — Iossifov et al. estimate 65 of them — it is particularly noteworthy that six genes were found to have a gene-disrupting de novo mutation in more than one individual with ASD, and many others genes are 'hit' by missense mutations more than once. These will be important leads for follow-up work.

Iossifov, I. et al. De novo gene disruptions in children on the autistic spectrum. Neuron 74, 285–299 (2012)