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. Interrogating these phenomena is difficult due to the high complexity of the LCR22s and the inaccurate representation of the LCRs across different reference genomes. Optical mapping techniques, which provide long-range chromosomal maps, could be used to unravel the complex duplicon structure. These techniques have already uncovered the hypervariability of the LCR22-A haplotype in the human population. Although optical LCR22 mapping is a major step forward, long-read sequencing approaches will be essential to reach nucleotide resolution of the LCR22s and map the crossover sites. Accurate maps and sequences are needed to pinpoint potential predisposing alleles and, most importantly, allow for genotype–phenotype studies exploring the role of the LCR22s in health and disease. In addition, this research might provide a paradigm for the study of other rare genomic disorders.