Evan Eichler and his colleagues at the University of Washington aim to perform the systematic discovery of single nucleotide variations (SNVs), insertions and deletions in DNA (indels) and structural variations within 160 genomes from 40 families in the Simons Simplex Collection (SSC).

The researchers selected families that have available DNA from both parents as well as one child with autism and one unaffected sibling. They selected individuals with autism in whom no obvious candidate mutation has been discovered by the sequencing of exomes — the coding portions of genomes — or analysis of copy number variations, which are deletions or duplications of large DNA segments.

The researchers aim to focus on validating all spontaneous, or de novo, genetic variation and publicly disseminating all data, including on inherited mutations. They plan to process data using a hybrid computational annotation model that entails the calling of SNVs, indels and CNVs. They will use an intersection of more routine genetic callers as well as more computational-intensive approaches, developed in the Eichler laboratory, that increase sensitivity for variant detection in complex regions of the genome. They aim to validate all de novo variants using a well-established protocol for targeting small segments of DNA (molecular inversion probes) for SNVs and indels, and a longstanding technique for measuring copy number by the intensity of probes in specific regions of the genome (array comparative genomic hybridization).

The team plans to publicly disseminate data via the National Database for Autism Research using standards previously established for the SSC exome-sequencing project.