Outside influences on CHD8 variant phenotypes, and more

Myriad contributions: Two new papers describe secondary influences on the autism-like traits that arise from CHD8 gene variants in mice. In the first study, comparing mice with heterozygous versus homozygous CHD8 variants revealed a gene dosage effect on behavior, brain structure and neural activity. The investigators also saw less sex specificity in the homozygous mice. In the second study, researchers sought to understand the heterogeneity of CHD8 variant effects in mice with different genetic backgrounds. They documented a range of pup-dam interactions and linked those to autism-like traits in weaned pups. Thus, genetic background, gene dose and early life experiences all appear to contribute to phenotypic variability in mouse models of autism.

Autism research spotted this week:

• “Risk for autism across generations” Biological Psychiatry
• “Determinants of functional burden pleiotropy and gene dosage responses across human traits” medRxiv
• “SHANK3 mutations disrupt olfactory valence coding across species, with cortical amygdala mechanisms identified in mice” Science Advances
• “NeuroDev: Etiology and experience of neurodevelopmental disorders in Kenya and South Africa” medRxiv
  See also: “African genetics study NeuroDev shares initial findings”
• “Modeling rare coding variation on chromosome X provides insight into the genetics and differential sex prevalence of autism spectrum disorder” medRxiv
• “An X-linked long non-coding RNA, PTCHD1-AS, and the core features of autism” Nature
• “SHANK3-anchored reverse phenotyping identifies a rare-variant-enriched cognitive-motor subgroup of autism” medRxiv
• “Brain charts for neuroanatomical sex differences across the human lifespan” bioRxiv