22q11.2 Low Copy Repeats Expanded in the Human Lineage

Area of Science:

• Genomics
• Human Evolution
• Primate Genetics

Background:

• Segmental duplications, or low copy repeats (LCRs), are complex genomic regions.
• Genes within LCRs are implicated in human brain development and evolution.
• The 22q11.2 locus contains eight LCRs (LCR22s), and rearrangements cause 22q11.2 deletion syndrome.

Purpose of the Study:

• To investigate LCR22 haplotype variability in non-human primates.
• To address sequence gaps in primate reference genomes using novel assembly techniques.
• To understand the evolutionary history of LCR22 expansion.

Main Methods:

• De novo assembly of the LCR22 region in non-human primates.
• Utilized optical mapping techniques for high-resolution genome analysis.
• Compared assembled sequences with existing reference genomes.

Main Results:

• Identified a conserved, ancient LCR22 haplotype across chimpanzees, bonobos, and rhesus monkeys with no intra-species variation.
• Discovered and corrected assembly errors and gaps in primate chromosome 22 reference sequences.
• Demonstrated that LCR22 expansion is a human-specific event.

Conclusions:

• The expansion of LCR22 is unique to the human lineage, potentially contributing to human evolution.
• Optical mapping provides a powerful tool for resolving complex genomic regions like LCR22.
• These findings pave the way for LCR22-specific functional studies and understanding 22q11.2 deletion syndrome variability.