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

Published version
Peer-reviewed

Type

Article

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Authors

Lombardo, Michael V  ORCID logo  https://orcid.org/0000-0001-6780-8619
Pramparo, Tiziano 
Gazestani, Vahid H 
Hagler, Donald J 

Abstract

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.

Description

Keywords

31 Biological Sciences, 3105 Genetics, Stem Cell Research, Neurosciences, Autism, Genetics, Pediatric, Brain Disorders, Mental Health, Intellectual and Developmental Disabilities (IDD), Biotechnology, Human Genome, Stem Cell Research - Nonembryonic - Human

Journal Title

Sci Adv

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

7

Publisher

American Association for the Advancement of Science (AAAS)
Sponsorship
Medical Research Council (MR/M009041/1)
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