We additionally analysed 5,819 homozygous deletions to search for gene knockouts occurring naturally in human populations. Among these we identified 240 genes (corresponding to 204 individual deletion sites) that, on the basis of the observation of homozygous losses in normal individuals, seem to be ‘dispensable’ (Supplementary Table 6). Most of the underlying deletions were found in more than one human population, and for only one (0.5%) we observed evidence for the putative involvement of uniparental disomy in the homozygosity (Supplementary Note). The majority (>80%) of these homozygous gene losses were novel compared to a previous analysis based on DGV variants19, or recent clinical genomics studies (Supplementary Note). As expected, genes affected by homozygous loss were not highly conserved and were relatively tolerant to other forms of genetic variation (RVIS = 0.74 compared to OMIM disease genes showing RVIS = 0.43; P = 9.4 × 10−25; Mann–Whitney test). Moreover, the set was functionally enriched for glycoproteins (Benjamini–Hochberg corrected P-value = 1.6 × 10−3, EASE (Expression Analysis Systematic Explorer) score) and genes harbouring immunoglobulin domains (Benjamini–Hochberg corrected P-value = 1.0 × 10−5, EASE score).
