02164nas a2200337   4500000000100000008004100001260001300042653002300055653003200078653003800110653002000148653002000168653001100188653001400199653001200213653002200225653001400247653002600261100001300287700001200300700001300312700001100325700001400336245009600350856011700446300001000563490000700573050001600580520121600596022001401812       2008                            d  c2008 May10aChromosome Mapping10aChromosomes, Human, Pair 1010aGenetic Predisposition to Disease10aHLA-DR Antigens10aHLA-DRB1 Chains10aHumans10aInfection10aleprosy10aLymphotoxin-alpha10aPhenotype10aPolymorphism, Genetic1 aRanque B1 aAlter A1 aSchurr E1 aAbel L1 aAlcaïs A00a[Leprosy: a paradigm for the study of human genetic susceptibility to infectious diseases].  uhttp://www.medecinesciences.org/index.php?option=com_article&access=doi&doi=10.1051/medsci/2008245491&Itemid=129  a491-70 v24  aRANQUE 20083 a<p>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.</p>  a0767-0974