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  • Title: A major gene controls leprosy susceptibility in a hyperendemic isolated population from north of Brazil.
    Author: Lázaro FP, Werneck RI, Mackert CC, Cobat A, Prevedello FC, Pimentel RP, Macedo GM, Eleutério MA, Vilar G, Abel L, Xavier MB, Alcaïs A, Mira MT.
    Journal: J Infect Dis; 2010 May 15; 201(10):1598-605. PubMed ID: 20388034.
    Abstract:
    BACKGROUND: Leprosy is a chronic infectious disease that affects 250,000 new individuals/year worldwide. Genetic analysis has been successfully applied to the identification of host genetic factors affecting susceptibility to leprosy; however, a consensus regarding its mode of inheritance is yet to be achieved. METHODS: We conducted a complex segregation analysis (CSA) on leprosy using data from the Prata Colony, an isolated, highly endemic former leprosy community located at the outskirts of the Brazilian Amazon. The colony offers large multiplex, multigenerational pedigrees composed mainly by descendents of a small number of original leprosy-affected families. Our enrollment strategy was complete ascertainment leading to the inclusion of the whole colony (2005 individuals, 225 of whom were affected) distributed in 112 pedigrees. CSA was performed using REGRESS software. RESULTS: CSA identified a best-fit codominant model, with a major gene accounting for the entire familial effect observed. The frequency of predisposing allele was estimated at 0.22. Penetrance for homozygous individuals for the predisposing allele >30 years old ranged from 56% to 85%, depending on sex. CONCLUSIONS: A strong major gene effect in the isolated, hyperendemic Prata Colony indicates enrichment of genetic risk factors, suggesting a population particularly suitable for leprosy gene identification studies.
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