title: A systematic characterization of genes underlying both complex and Mendelian diseases.
abstract: Traditionally, genetic disorders have been classified as either Mendelian diseases or complex diseases. This nosology has greatly benefited genetic counseling and the development of gene mapping strategies. However, based on two well-established databases, we identified that 54% (524 of 968) of the Mendelian disease genes were also involved in complex diseases, and this kind of genes has not been systematically analyzed. Here, we classified human genes into five categories: Mendelian and complex disease (MC) genes, Mendelian but not complex disease (MNC) genes, complex but not Mendelian disease (CNM) genes, essential genes and OTHER genes. First, we found that MC genes were associated with more diseases and phenotypes, and were involved in more complex protein-protein interaction network than MNC or CNM genes on average. Secondly, MC genes encoded the longest proteins and had the highest transcript count among all gene categories. Especially, tissue specificity of MC genes was much higher than that of any other gene categories (P < 7.5 × 10(-5)), although their expression level was similar to that of essential genes. Thirdly, evidences from different aspects supported that MC genes have been subjected to both purifying and positive selection. Interestingly, functions of some human disease genes might be different from those of their orthologous genes in non-primate mammalians since they were even less conserved than OTHER genes. The significant over-representation of copy number variations (CNVs) in CNM genes suggested the important roles of CNVs in complex diseases. In brief, our study not only revealed the characteristics of MC genes, but also provided new insights into the other four gene categories.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences and Max Planck Society Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031 Shanghai, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Jin
authors.forename: Pengfei
authors.initials: P
authors.lastname: Qin
authors.forename: Haiyi
authors.initials: H
authors.lastname: Lou
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Shuhua
authors.initials: S
authors.lastname: Xu
mesh_terms: D004194:Disease / Q000235:genetics*; D019143:Evolution, Molecular; D018628:Gene Dosage; D005796:Genes; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D011506:Proteins