Genet Med. 2025 Oct 21:101614. doi: 10.1016/j.gim.2025.101614. Online ahead of print.
ABSTRACT
PURPOSE: The genomic architecture of 22q11.2 Deletion Syndrome (22q11.2DS) has primarily been studied in White populations, despite evidence suggesting a lower prevalence in Black individuals. This study aims to improve our understanding of the population-specific organization of 22q11.2 genomic structures.
METHODS: Optical mapping data from 106 genomes, representing various Black and White individuals, were analyzed to assess the structure and variation of the 22q11.2 low copy repeats (LCR22s).
RESULTS: Extensive variability in copy number and orientation of LCR22 elements was observed between Black and White genomes. Several novel copy number variants (CNVs) and haplotype configurations were identified, some being private or more prevalent within specific groups. Notably, CNV diversity was particularly striking among Black genomes. Comparisons of Black and White families with de novo 22q11.2DS probands revealed unique non-allelic homologous recombination (NAHR) scenarios, with Black families exhibiting recombination patterns not previously observed.
CONCLUSION: Perhaps the unique and highly variable LCR22 haplotype configurations in Black individuals contribute to the lower observed prevalence of 22q11.2DS by inhibiting the likelihood of NAHR, the mechanism that leads to the syndrome.
PMID:41137608 | DOI:10.1016/j.gim.2025.101614
