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Neurodevelopmental disorders: 2021 update.

Alfonsa Zamora-Moratalla1, Maria Martínez de Lagrán1, Mara Dierssen1,2,3

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Summary

Understanding the causes of neurodevelopmental disorders (NDDs) is key. Advances in genomics and modeling tools are revealing genetic factors and neuropathological mechanisms for NDDs like autism spectrum disorder.

Keywords:
ASDAutism spectrum disorderMicrobiomeNeurodegenerative disordersNext generation sequencingPreterm birth

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Neurodevelopmental disorders (NDDs) encompass a range of conditions including autism spectrum disorder (ASD), developmental delay, intellectual disability (ID), and attention-deficit/hyperactivity disorder (ADHD).
  • Determining the etiology and risk factors for NDDs remains a significant challenge in the field.
  • These disorders are characterized by neurodevelopmental dysfunction, cognitive impairments, and a high prevalence of neuropsychiatric outcomes.

Purpose of the Study:

  • To summarize recent advances in understanding the genetic architecture and neuropathological mechanisms of NDDs.
  • To highlight the role of emerging technologies in NDD research.
  • To provide insight into the developmental origins and molecular pathology of neurodevelopmental disorders.

Main Methods:

  • Analysis of large-scale human genomics and sequencing studies.
  • Investigation of genomic DNA methylation patterns (episignatures) and polygenic risk.
  • Recognition of the contribution of de novo somatic mutations.
  • Advancements in modeling tools for NDDs.
  • Application of in vivo gene editing and single-cell RNA-sequencing (scRNA-seq).

Main Results:

  • Genomic studies are revealing diverse mechanisms underlying NDDs, including unique episignatures and polygenic contributions.
  • The role of de novo somatic mutations in neurodevelopmental diseases is increasingly recognized.
  • New modeling tools and advanced molecular assays are improving the resolution of genetic and neuropathological investigations.

Conclusions:

  • Genomic insights are beginning to elucidate the genetic architecture of NDDs.
  • Advanced modeling tools and techniques like scRNA-seq are crucial for understanding NDD origins and mechanisms.
  • Progress in these areas promises to enhance our comprehension of neurodevelopmental disorder neuropathology.