title: Integrative analyses of leprosy susceptibility genes indicate a common autoimmune profile.
abstract: BACKGROUND
  Leprosy is an ancient chronic infection in the skin and peripheral nerves caused by Mycobacterium leprae. The development of leprosy depends on genetic background and the immune status of the host. However, there is no systematic view focusing on the biological pathways, interaction networks and overall expression pattern of leprosy-related immune and genetic factors.
  
  
  OBJECTIVE
  To identify the hub genes in the center of leprosy genetic network and to provide an insight into immune and genetic factors contributing to leprosy.
  
  
  METHODS
  We retrieved all reported leprosy-related genes and performed integrative analyses covering gene expression profiling, pathway analysis, protein-protein interaction network, and evolutionary analyses.
  
  
  RESULTS
  A list of 123 differentially expressed leprosy related genes, which were enriched in activation and regulation of immune response, was obtained in our analyses. Cross-disorder analysis showed that the list of leprosy susceptibility genes was largely shared by typical autoimmune diseases such as lupus erythematosus and arthritis, suggesting that similar pathways might be affected in leprosy and autoimmune diseases. Protein-protein interaction (PPI) and positive selection analyses revealed a co-evolution network of leprosy risk genes.
  
  
  CONCLUSIONS
  Our analyses showed that leprosy associated genes constituted a co-evolution network and might undergo positive selection driven by M. leprae. We suggested that leprosy may be a kind of autoimmune disease and the development of leprosy is a matter of defect or over-activation of body immunity.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China. Electronic address: zhangdengfeng@mail.kiz.ac.cn.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China. Electronic address: yaoyg@mail.kiz.ac.cn.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D015551:Autoimmunity / Q000235:genetics*; D019295:Computational Biology; D030541:Databases, Genetic; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D007918:Leprosy / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D009167:Mycobacterium lepraemurium / Q000276:immunology; D010641:Phenotype; D060066:Protein Interaction Maps
chemical_list: D005819:Genetic Markers
keywords: Autoimmune; Enrichment; Leprosy; Network; Susceptibility gene