Atypical genomic cortical patterning in autism with poor early language outcome.

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Lombardo, Michael V  ORCID logo
Pramparo, Tiziano 
Gazestani, Vahid H 
Hagler, Donald J 

Cortical regionalization develops via genomic patterning along anterior-posterior (A-P) and dorsal-ventral (D-V) gradients. Here, we find that normative A-P and D-V genomic patterning of cortical surface area (SA) and thickness (CT), present in typically developing and autistic toddlers with good early language outcome, is absent in autistic toddlers with poor early language outcome. Autistic toddlers with poor early language outcome are instead specifically characterized by a secondary and independent genomic patterning effect on CT. Genes involved in these effects can be traced back to midgestational A-P and D-V gene expression gradients and different prenatal cell types (e.g., progenitor cells and excitatory neurons), are functionally important for vocal learning and human-specific evolution, and are prominent in prenatal coexpression networks enriched for high-penetrance autism risk genes. Autism with poor early language outcome may be explained by atypical genomic cortical patterning starting in prenatal development, which may detrimentally affect later regional functional specialization and circuit formation.

31 Biological Sciences, 3105 Genetics, Autism, Stem Cell Research, Biotechnology, Neurosciences, Mental Health, Stem Cell Research - Nonembryonic - Human, Intellectual and Developmental Disabilities (IDD), Pediatric, Genetics, Human Genome, Brain Disorders
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Sci Adv
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American Association for the Advancement of Science (AAAS)
Medical Research Council (MR/M009041/1)