For the past two decades, autism researchers have tried to dissect autism’s vast diversity by way of a ‘genetics-first’ approach: They study groups of autistic people with similar single-gene mutations or chromosomal alterations, who also often share physical and behavioral traits.
But many similarities exist across people with different chromosomal alterations — including copy number variants (CNVs) or structural variants that duplicate, delete, insert or invert large chunks of genes. For example, autism, intellectual disability and motor issues all characterize the neurodevelopmental syndromes associated with duplications in chromosome 15 (dup15q), ring-like rearrangements of chromosome 14 (ring 14) and a range of alterations in a chromosomal region called 8p.
A new organization seeks to build knowledge around these commonalities among people with different CNVs. Called the Commission on Novel Technologies for Neurodevelopmental Copy Number Variants, or the CNV Commission for short, the group was co-founded in 2020 by the leaders of three family groups affected by three rare chromosomal variants: the Dup15q Alliance, Ring 14 USA and Project 8p.
The CNV Commission has convened a team of scientists and published its road map in the American Journal of Human Genetics this month.
This interview has been edited for length and clarity.
Spectrum: How did the CNV Commission get started?
Vanessa Vogel-Farley: We all knew researchers doing fantastic work related to copy number variants and structural variants, but there was no new blood coming in. Our three groups were awarded a Rare As One grant from the Chan Zuckerberg Initiative to bring together the best minds to get their insight into how they would approach this.
Yssa DeWoody: It culminated in a big conference in July 2021. The scientists met the day before a joint family conference among our three organizations, so they were able to not only have their time together to lay out the steps in this road map, but also to stick around and meet the families.
S: The rationale for a genetics-first approach was that it can help minimize the heterogeneity that confounds autism research. By looking for commonalities among people with different CNVs, are you walking that approach back in some ways?
YD: ‘Lumpers’ versus ‘splitters’ is a classic problem. At some point, there’s good to be had by looking at pheno