Genes dysregulated in the blood of people with Williams syndrome are enriched in protein-coding genes positively selected in humans.

Williams syndrome is a complex condition resulting from the heterozygous deletion of nearly 30 genes in chromosome 7. However, precise genotype-to-phenotype mappings are not available for most of its distinctive features. Because WS entails changes in the expression patterns of multiple genes outside the WS region, it can be expected that many other genes besides the deleted genes contribute to this condition. In this paper, we hypothesise that genes that have changed recently in our history could account for some key aspects of the WS phenotype, because of the robust link that exists between human evolution and complex, human-specific diseases. Supporting this view, we have found that protein-coding genes that are dysregulated in the blood of subjects with WS are significantly enriched in protein-coding genes that have been positively selected in our species compared to extinct hominins. These genes play biological roles and are expressed in body regions of relevance for the WS phenotype. We conclude that the genes we highlight in the paper should be regarded as important etiological factors of the WS clinical profile.