Individuals with autism frequently display accelerated brain growth during infancy and a larger brain size that is also associated with increased symptom severity. Given the widely documented heritability suggesting that autism is predominantly a genetic condition, and the well-established link between autism and abnormally accelerated brain-growth patterns, genes involved in brain growth are excellent candidates for better understanding autism.

James Sikela and his team at the University of Colorado, Denver identified one such candidate, the DUF1220 protein domain. Protein domains are conserved segments of a protein that typically carry out important biological functions. Sikela’s team found that DNA sequences that encode DUF1220 domains show the largest human-specific increase in copy number of any gene sequences in the human genome. In addition, the number of DUF1220 copies in the genome closely parallels differences in brain size among primates and humans. However, due to their high copy number (more than 270 copies) in people, DUF1220 domains have not been directly investigated in previous genome-wide studies searching for important autism genes.

As part of Sikela’s interest in the genetics of autism, his team has been measuring the number of copies of DUF1220 found in the genomes of individuals with autism. They found in 2014 that that increasing copy number of the DUF1220 subtype CON1 is associated in a linear dose-response manner with increasing severity of each of the three primary symptoms of autism: impaired social reciprocity, impaired communicative ability and increased repetitive behaviors¹.

Sikela and his team believe that this discovery represents a new direction for studies aimed at understanding the genetic factors contributing to autism severity. They plan to expand on these findings by investigating the association between DUF1220 CON1 copy number and autism severity in a larger, independent autism sample, and by investigating its involvement in multiplex compared with simplex cases of autism.