Fifty years ago, the first identification of a non Mendelian genetic contribution to the development of a common infectious disease, i.e. the association between malaria and sickle-cell trait, was shown using a supervised approach which tests a limited number of candidate genes selected by hypothesis. Since then, the few genes that were convincingly associated with susceptibility to human infectious diseases were identified following the same strategy. The study of leprosy has contributed to modifying this way of thinking. In the absence of a satisfying experimental model and because of the impossibility to grow the causative agent in vitro, the candidate gene approach has turned out to be of limited interest. Conversely, positional cloning led to the identification of two major genes involved in the control of the disease, establishing for the first time the oligogenic nature of a human genetic contribution to an infectious disease. It is likely that these major results obtained in leprosy and the recent burst of genomic tools will make the genome-wide screening (functional or positional) the main strategy of dissection of the genetic susceptibility to many common infectious diseases.
BT - Medecine sciences : M/S C1 - http://www.ncbi.nlm.nih.gov/pubmed/18466726?dopt=Abstract CN - RANQUE 2008 DA - 2008 May DO - 10.1051/medsci/2008245491 IS - 5 J2 - Med Sci (Paris) LA - fre N2 -Fifty years ago, the first identification of a non Mendelian genetic contribution to the development of a common infectious disease, i.e. the association between malaria and sickle-cell trait, was shown using a supervised approach which tests a limited number of candidate genes selected by hypothesis. Since then, the few genes that were convincingly associated with susceptibility to human infectious diseases were identified following the same strategy. The study of leprosy has contributed to modifying this way of thinking. In the absence of a satisfying experimental model and because of the impossibility to grow the causative agent in vitro, the candidate gene approach has turned out to be of limited interest. Conversely, positional cloning led to the identification of two major genes involved in the control of the disease, establishing for the first time the oligogenic nature of a human genetic contribution to an infectious disease. It is likely that these major results obtained in leprosy and the recent burst of genomic tools will make the genome-wide screening (functional or positional) the main strategy of dissection of the genetic susceptibility to many common infectious diseases.
PY - 2008 SP - 491 EP - 7 T2 - Medecine sciences : M/S TI - [Leprosy: a paradigm for the study of human genetic susceptibility to infectious diseases]. TT - La lèpre : Un paradigme pour l’étude de la prédisposition génétique aux maladies infectieuses UR - http://www.medecinesciences.org/index.php?option=com_article&access=doi&doi=10.1051/medsci/2008245491&Itemid=129 VL - 24 SN - 0767-0974 ER -