Functional assessment of the "two-hit" model for neurodevelopmental defects in Drosophila and X. laevis.

ABSTRACT: We previously identified a deletion on chromosome 16p12.1 that is mostly inherited and associated with multiple neurodevelopmental outcomes, where severely affected probands carried an excess of rare pathogenic variants compared to mildly affected carrier parents. We hypothesized that the 16p12.1 deletion sensitizes the genome for disease, while "second-hits" in the genetic background modulate the phenotypic trajectory. To test this model, we examined how neurodevelopmental defects conferred by knockdown of individual 16p12.1 homologs are modulated by simultaneous knockdown of homologs of "second-hit" genes in Drosophila melanogaster and Xenopus laevis. We observed that knockdown of 16p12.1 homologs affect multiple phenotypic domains, leading to delayed developmental timing, seizure suscep

SUBMITTER: Pizzo L 

PROVIDER: S-EPMC8049494 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature