Multiple paralogues and recombination mechanisms contribute to the high incidence of 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder.

Multiple paralogues and recombination mechanisms drive the high incidence of 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder.

The 22q11.2 Low Copy Repeats.

LCR22s are among the most complex loci in the human genome and are susceptible to nonallelic homologous recombination. This can lead to a variety of genomic disorders, including deletions, duplications, and translocations, of which the 22q11.2 deletion syndrome is the most common in humans.

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

Segmental duplications or low copy repeats (LCRs) constitute duplicated regions interspersed in the human genome, currently neglected in standard analyses due to their extreme complexity. Recent functional studies have indicated the potential of genes within LCRs in synaptogenesis, neuronal migration, and neocortical expansion in the human lineage. One of the regions with the highest proportion of duplicated sequence is the 22q11.

Atypical chromosome 22q11.2 deletions are complex rearrangements and have different mechanistic origins.

The majority (99%) of individuals with 22q11.2 deletion syndrome (22q11.2DS) have a deletion that is caused by non-allelic homologous recombination between two of four low copy repeat clusters on chromosome 22q11.

The 22q11 low copy repeats are characterized by unprecedented size and structural variability.

Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The Chromosome 22 LCRs (LCR22s) mediate nonallelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS). However, LCR22s are among the most complex regions in the genome, and their structure remains unresolved.