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Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

Amy Lin1, Christopher R K Ching1,2, Ariana Vajdi1

  • 1Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California 90095.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|May 25, 2017
PubMed
Summary
This summary is machine-generated.

Brain structure varies with 22q11.2 gene dosage. Deletions and duplications impact intracranial volume, gray/white matter, and cortical surface area, influencing neurodevelopmental disorder risk.

Keywords:
autism spectrum disorderchromosome 22copy number variantneurodevelopmentpsychosisstructural neuroimaging

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Reciprocal chromosomal rearrangements at 22q11.2 are linked to neurodevelopmental disorders.
  • 22q11.2 deletion is a major genetic risk for schizophrenia, while duplication is linked to autism.

Purpose of the Study:

  • To investigate the effects of 22q11.2 gene dosage on human brain structure.
  • To establish the first evidence of gene-dose-dependent brain phenotypes in this region.

Main Methods:

  • Studied 143 human subjects: 66 with 22q11.2 deletions (22q-del), 21 with 22q11.2 duplications (22q-dup), and 56 controls.
  • Analyzed intracranial volume, gray/white matter volume, cortical surface area, and thickness.
  • Utilized novel subcortical shape analysis.

Main Results:

  • Gene dosage positively correlated with intracranial volume, gray/white matter, and cortical surface area (deletion < control < duplication).
  • Gene dosage negatively correlated with mean cortical thickness (deletion > control > duplication).
  • Observed widespread cortical surface area changes and localized thickness differences, extending to subcortical regions like the hippocampus, caudate, and amygdala.

Conclusions:

  • The 22q11.2 locus exhibits gene-dose-dependent effects on brain morphology.
  • Copy number variation at 22q11.2 impacts brain structure early in development, affecting cortical surface area most broadly.
  • Findings highlight the role of 22q11.2 in typical brain development and neurodevelopmental disorders.