NeuroDev research maps beforehand unseen genetic variation in Africa
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euroDev launched in 2018, with the goal of gathering information from more than 5,000 participants in South Africa and Kenya, including 1,800 children with developmental differences. The preprint shares data on the first wave of participants, which includes 521 children with neurodevelopmental conditions, along with 739 of their parents and 255 unrelated, neurotypical children.
Each child underwent a four-hour evaluation, and all participants provided genetic samples for whole-exome sequencing. Many South African families also shared photos of their children. For some conditions, these pictures are the first photographed cases in people with African ancestry.
What they’re doing is an extraordinary heavy lift and is very interesting,
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Daniel Geschwind
The NeuroDev children with neurodevelopmental conditions had more rare genetic variants than people with the same conditions in other ancestral groups, the results show, likely due to Africa’s greater genetic diversity and underrepresentation in databases.
Nearly all of the children with neurodevelopmental conditions met the criteria for intellectual disability or developmental delay, and roughly half met the criteria for autism. Children in about 22 percent of families had a genetic diagnosis, with known pathogenic or likely pathogenic variants. An additional 4 percent had variants of uncertain significance in genes linked to neurodevelopmental conditions.
Another 16.5 percent had variants of uncertain significance with no known links to neurodevelopmental conditions. The lack of population-level data makes it difficult to know whether the variants are pathogenic or benign, says Emily O’Heir, a NeuroDev investigator and genomic variant analyst at the Broad Institute.
The team submitted those 80 cases to the database MatchMaker Exchange. The database matched 32 of them to other reported cases, and the NeuroDev team is now collaborating on multiple reports describing new potential gene-disease links.
“That was a very good move,” says Daniel Geschwind, professor of neurology, psychiatry and human genetics at the University of California, Los Angeles, who was not involved in the work. “These may or may not be pathogenic. Time will tell.”
Geschwind says it would be interesting to compare the NeuroDev results with available data on African Americans with autism, including his own work. Even the groups from Kenya and South Africa were strikingly different from each other, he says, likely because of how participants were recruited.
“What they’re doing is an extraordinary, heavy lift and is very interesting,” Geschwind adds.
