02019nas a2200241   4500000000100000008004100001653001200042653002000054653001400074100001200088700001500100700001300115700001800128700001900146700001400165700001800179700001200197245008000209300001100289490000700300520145600307022001401763       2015                            d10aleprosy10aGenetic factors10aPhenotype1 aSauer M1 aSalomão H1 aRamos GB1 aD Espindula H1 aRodrigues RS A1 aMacedo WC1 aSindeaux RH M1 aMira MT00aGenetics of leprosy: Expected and unexpected developments and perspectives.  a99-1070 v333 a<p>A solid body of evidence produced over decades of intense research supports the hypothesis that leprosy phenotypes are largely dependent on the genetic characteristics of the host. The early evidence of a major gene effect controlling susceptibility to leprosy came from studies of familial aggregation, twins, and Complex Segregation Analysis. Later, linkage and association analysis, first applied to the investigation of candidate genes and chromosomal regions and more recently, to genome-wide scans, have revealed several leukocyte antigen complex and nonleukocyte antigen complex gene variants as risk factors for leprosy phenotypes such as disease per se, its clinical forms and leprosy reactions. In addition, powerful, hypothesis-free strategies such as Genome-Wide Association Studies have led to an exciting, unexpected development: Leprosy susceptibility genes seem to be shared with Crohn's and Parkinson's diseases. Today, a major challenge is to find the exact variants causing the biological effect underlying the genetic associations. New technologies, such as Next Generation Sequencing that allows, for the first time, the cost and time-effective sequencing of a complete human genome, hold the promise to reveal such variants. Strategies can be developed to study the functional effect of these variants in the context of infection, hopefully leading to the development of new targets for leprosy treatment and prevention.</p>
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