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Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

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Large-scale genetic mapping for human brain asymmetry.

Zhiqiang Sha¹, Clyde Francks²

¹Language & Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands.

Handbook of Clinical Neurology

|March 12, 2025

Summary

Recent studies link specific genes to human brain asymmetry and handedness, primarily active during early development. Understanding these genetic links may offer insights into neurodevelopmental and psychiatric disorders.

Keywords:

Brain asymmetry Chirality Gene expression Genetic association Genomics Hemispheric specialization Laterality Microtubules Neurodevelopment

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Area of Science:

Neuroscience
Genetics
Developmental Biology

Background:

Left-right brain asymmetry is crucial for cognitive functions like language and motor control.
Alterations in brain asymmetry are observed in psychiatric conditions.
Recent genetic studies have identified specific genes associated with brain asymmetry and handedness variations.

Purpose of the Study:

To summarize recent advances in identifying genes linked to human brain asymmetry.
To explore the developmental origins and cellular mechanisms of brain asymmetry.
To investigate the connection between genes influencing asymmetry and psychiatric/neurologic disorders.

Main Methods:

Large-scale genome-wide association studies (GWAS) in large participant cohorts (16,000 to over 1.5 million).
Analysis of gene expression patterns during embryonic and fetal development.
Review of genetic associations with psychiatric and neurologic conditions.

Main Results:

Identification of specific genes influencing human brain asymmetry and handedness.
Implicated genes are often most active during early brain development.
Several identified genes encode microtubule or microtubule-associated proteins, crucial for cytoskeleton structure.
Associations found between polygenic risk for autism and schizophrenia and structural brain asymmetry.

Conclusions:

Genes affecting brain asymmetry are primarily active during early development, influencing the brain's left-right axis.
Understanding these genetic mechanisms is key to deciphering the etiology of neurodevelopmental and psychiatric disorders.
Further research into developmental pathways may help define subtypes of brain disorders based on hemispheric specialization.