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

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

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Type
Article
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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.

Publication Date
2021-09-03
Online Publication Date
2021-09-03
Acceptance Date
Keywords
31 Biological Sciences, 3105 Genetics, Neurosciences, Intellectual and Developmental Disabilities (IDD), Autism, Pediatric, Brain Disorders, Genetics, Stem Cell Research, Mental Health, Human Genome, Biotechnology, Stem Cell Research - Nonembryonic - Human
Journal Title
Sci Adv
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)