Both genes involved in XLMR and those associated with other diseases are characterized by longer protein-coding sequences (P < 0.01), larger genomic footprints (P < 0.02) and greater numbers of exons (P < 0.01) than X-chromosome genes not associated with a disease. In part, this may be attributable to ascertainment bias. Larger genes are likely to have a higher mutation rate, because they constitute a bigger target for mutational processes, and therefore may have a greater prevalence of disease-causing mutations in the population. The higher the prevalence of disease-causing mutations, the more likely a gene is to have been identified as a disease gene. The comparatively large size of disease genes generally has previously been reported31. Significant differences between the three groups of genes were not found in levels of brain expression, tolerance of common sequence variation or the presence of paralogs in the human genome.
