Further understanding human disease genes by comparing with housekeeping genes and other genes

In the absence of a set of well defined human essential genes, we consider a set of 1,789 ubiquitously expressed human genes (UEHGs), also known as housekeeping genes, as an approximation. We demonstrate that UEHGs are very likely to contain a large proportion of essential genes. We show that the UEHGs, disease genes and other genes are different in their evolutionary conservation rates, DNA coding lengths, gene functions, etc. Our findings systematically confirm that disease genes have an intermediate essentiality which is less than housekeeping genes but greater than other human genes.The human genome may contain thousands of essential genes having features which differ significantly from disease and other genes. We propose to classify them as a unique group for comparisons of disease genes with non-disease genes. This new way of classification and comparison enables us to have a clearer understanding of disease genes.Identification of novel genes associated with human diseases is among the most critical tasks in medical research. Towards this goal, various features have been compared between heritable disease genes and non-disease genes [1-4]. Although most findings were consistent with each other, a few conflicting results showed up. For example, Smith et al. [3] found that disease genes evolved with higher nonsynonymous/synonymous substitution rate ratios (Ka/Ks) than non-disease genes, but Huang et al. [4] found no such significant differences. One common problem with these studies is that human essential genes were ignored and simply grouped together with other non-disease genes. Essential genes are genes whose functions are necessary for the organism to survive and reproduce. Since the disruption of essential genes' function will cause fatal consequences, they should be regarded as the most severe "disease" genes. Therefore, comparing disease genes to a mixture of essential and non-disease genes will reduce the clarity of the signals of the disease-related f