Figure 2

The array of mouse and human deafness loci and genes. An analysis of the distribution of identified mouse and human non-syndromic sensorineural genes or loci and their overlap, on the basis of the identification of conserved orthologous genes or conserved map positions (in the case of loci for which the underlying gene has not been identified). A large number of human sensorineural genes (14) or mapped sensorineural loci (29) have been identified for which there is no mouse counterpart (right side of the figure). A corresponding situation exists for the mouse (left side of the figure). There are 18 loci in three classes, however, for which common genes or loci have been identified in mouse and human: 10 mutant loci for which genes have been identified in both mouse and human; 6 mouse mutant loci for which the gene has been identified and for which there appear to be homologous human loci, on the basis of conserved map position); and 2 mapped mouse mutant loci for which the gene has not been identified but there appear to be homologous human loci (based on conserved map position). Given the number of loci identified in these overlapping classes, we can make a determination of the total number of loci in mammals that might lead to non-syndromic hearing loss. N, the total number of genes in the mammalian set, is given by: N = M × H / C, where M is the total number of mouse loci assayed, Hthe total number of human loci assayed and C the total number of loci held in common. Thus, with current data, N = 36 × 63/18 = 126. This estimate is very conservative and is likely to be an underestimate for two reasons. Firstly, identifying orthologous loci on the basis of conserved map position is relatively crude and leads to a potential inflation in the number of overlapping loci. Secondly, mutant loci for which genes have been identified in both mouse and human are not ascertained on a random basis. Rather, once a gene has been cloned in one species, significant effort is expended to identify orthologous genes and mutations in the other species.