Genetic basis of phenotypic variability in 16p11.2 deletion or duplication

Evan Eichler and his colleagues are investigating the genetics underlying the variability of disease associated with deletion or duplication of chromosomal region 16p11.2. They plan to look for high-impact risk factors for autism in participants with variants both within and outside the 16p11.2 region.

Their investigation will include a systematic characterization of additional large copy number variants — duplications or deletions of DNA segments. The researchers also aim to characterize rare and disruptive mutations in autism candidate genes and differences in the breakpoints — the locations where 16p11.2 deletion or duplication occurs — among the participants.

Eichler and his team hypothesize that individuals carrying additional disruptive or larger mutations will have more severe outcomes compared with those carrying only the deletion or duplication.

This finding could explain why some individuals carrying the 16p11.2 deletion are severely afflicted with autism, mental retardation and seizures, whereas others can be relatively high‐functioning and live more normal lives.

The results have the potential to improve diagnosis, counseling and management of autism and to provide insight into its genetic basis. In addition, the research will generate a genetic resource for better tracking of the samples from the Simons Variation in Individuals Project and assist in the correct interpretation of functional datasets generated from these samples.