02762nas a2200517 4500000000100000008004100001260001600042653001500058653001000073653001200083653001100095653001000106653002100116653002100137653001100158653003800169653001700207653001500224653001100239653001100250653002000261653001200281653000900293653001600302653001300318653001600331100001500347700001500362700001400377700001200391700001800403700001500421700001300436700001700449700001200466700001100478700001300489700001400502700001200516245010900528856010900637300001300746490000800759520146300767022001402230 2010 d c2010 May 1510aAdolescent10aAdult10aAlleles10aBrazil10aChild10aChild, Preschool10aEndemic Diseases10aFemale10aGenetic Predisposition to Disease10aHeterozygote10aHomozygote10aHumans10aInfant10aInfant, Newborn10aleprosy10aMale10aMiddle Aged10aPedigree10aYoung Adult1 aLázaro FP1 aWerneck RI1 aMackert C1 aCobat A1 aPrevedello FC1 aPimentel R1 aMacedo G1 aEleutério M1 aVilar G1 aAbel L1 aXavier M1 aAlcaïs A1 aMira MT00aA major gene controls leprosy susceptibility in a hyperendemic isolated population from north of Brazil. uhttp://jid.oxfordjournals.org/content/201/10/1598.full.pdf+html?sid=47cedf8c-bfc3-4c96-b6d6-1d4d56c1dec5 a1598-6050 v2013 a
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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