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Complex mosaic structural variations in human fetal brains.

Shobana Sekar¹, Livia Tomasini², Christos Proukakis³

¹Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

Genome Research

|October 30, 2020

Summary

This summary is machine-generated.

Mosaic structural variants (SVs) are present in developing human brain cells, originating from replication errors during mid-neurogenesis. These SVs, though rare, impact a significant portion of the genome, potentially influencing cell function.

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Area of Science:

Genetics
Neuroscience
Developmental Biology

Background:

Somatic mosaicism, including single nucleotide variants (SNVs), is common in human brain cells.
Previous research quantified mosaic SNVs but not structural variations in the fetal brain.

Purpose of the Study:

To investigate the presence and characteristics of mosaic structural variants (SVs) in the developing human brain.
To determine the origin and potential functional impact of these mosaic SVs.

Main Methods:

Clonal sequencing of human fetal brain cells.
Identification and breakpoint resolution of kilobase-scale mosaic SVs.
Reanalysis of public single-nucleus data from adult brain neurons.

Main Results:

Four mosaic SVs were discovered and validated in fetal brains, characterized by deletions and rearrangements, often with microhomologies at breakpoints.
One SV originated around 14 weeks postconception and was found in multiple clones.
No large-scale mosaic copy number variants (CNVs) were detected in fetal brains, but extrachromosomal circular DNA was observed in adult neurons.
Mosaic SVs affect a substantial number of genomic bases, comparable to SNVs.

Conclusions:

Mosaic structural variants exist in the developing human brain, likely arising during mid-neurogenesis.
These SVs, while less frequent than SNVs, have significant genomic impact and may influence neuronal function.