Gaspar D A, Matioli S R, Pavanello R C, Araújo B C, André M, Steman S, Otto P A, Passos-Bueno M R
Centro de Estudos do Genoma Humano, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Genet Epidemiol. 2002 Nov;23(4):364-74. doi: 10.1002/gepi.10189.
The BCL3 gene has been considered a susceptibility locus for nonsyndromic cleft lip with or without cleft palate (NSCL/P), based on association and linkage studies in some populations. We evaluated an intragenic marker at the BCL3 gene and the microsatellite D19S178 (1.1 cM distant from the BCL3 gene) among 98 infants born with NSCL/P and their parents, using the transmission disequilibrium test (TDT) and a method for haplotype analysis. Our analysis, based on BCL3 alleles, revealed the existence of a marginal association of allele 135pb of the BCL3 gene with NSCL/P (chi(2)=3.60; P=0.058; 1 df), with a major effect in female (chi(2)=5.77; P=0.016; 1 df) and in familial cases (chi(2)=3.79; P=0.051; 1 df). However, the haplotype analysis detected no significant segregation distortion, even if the alleles of the D19S178 were grouped into two classes. These findings support previous findings that BCL3 plays a role in the etiology of NSCL/P as an allele of low penetrance or as a modifier locus. We hypothesize that there might be more than one mutation in this gene associated with NSCL/P, or alternatively, that more than one mutation has arisen associated with the 135-bp allele. Genet. Epidemiol. 23:364-374, 2002
基于在一些人群中的关联研究和连锁研究，BCL3基因被认为是伴或不伴腭裂的非综合征性唇裂（NSCL/P）的一个易感基因座。我们使用传递不平衡检验（TDT）和单倍型分析方法，对98例患有NSCL/P的婴儿及其父母进行了BCL3基因内标记和微卫星D19S178（距离BCL3基因1.1 cM）的评估。基于BCL3等位基因的分析显示，BCL3基因的135pb等位基因与NSCL/P存在边缘关联（χ² = 3.60；P = 0.058；1 df），在女性中（χ² = 5.77；P = 0.016；1 df）和家族性病例中（χ² = 3.79；P = 0.051；1 df）有主要影响。然而，即使将D19S178的等位基因分为两类，单倍型分析也未检测到显著的分离畸变。这些发现支持了先前的研究结果，即BCL3作为低外显率等位基因或修饰基因座在NSCL/P的病因学中起作用。我们假设该基因可能存在不止一个与NSCL/P相关的突变，或者，与135-bp等位基因相关出现了不止一个突变。《遗传流行病学》23:364 - 374, 2002
