Figure 3. Genomic organization of the Williams syndrome critical region.

The vast majority of Williams syndrome (WS) deletions (~90%) span a 1.55-million base pair (Mb) region encompassing 25–27 protein-coding genes in the Williams syndrome critical region (WSCR) on chromosome 7q11.23, with the remainder being slightly larger (1.83 Mb)³⁹. The larger, less common deletion occurs between low-copy repeats (LCRs) designated as ‘A blocks’, which are present in the great apes, whereas the smaller, more common deletion occurs between ‘B blocks’, which are only present in humans. B blocks originate from a more recent evolutionary duplication event and have a higher sequence identity than A blocks⁴⁰. The WS deletion commonly occurs through non-allelic homologous recombination between B block sequences in direct orientation with respect to each other³⁹; however, recombination between B blocks in an inverted orientation also occurs, resulting in inversion of the intervening chromosome segment⁴². Smaller, atypical deletions occur infrequently but can provide valuable insight into the genotype–phenotype relationship^{59,62,138–140}. Several names exist for many of the genes mapping to WSCR (see ²⁹³and https://www.ncbi.nlm.nih.gov/gene/). ID, intellectual disability.

Note: Figure 3 was drawn by the Nature Reviews Disease Primers art editor and permission for reproduction of the final figure was not granted by the publisher. This material is labeled as Fig. 2 in the published version of the paper DOI: 10.1038/s41572-021-00276-z