MOLECULAR AND EPIDEMIOLOGICAL STUDIES OF WAARDENBURG SYNDROME

我们进行了连锁分析和基因座异质性检验 使用来自2q35-37的9个DNA标记的Waardenburg综合征(WS) 与候选基因紧密连锁的高度多态的微卫星 Pax3基因座。PAX3对14个WS 1型(WS1)家系的分析产生了一个 假设最大LOD得分为27.81，theta=0.010，theta m=0.007 同质性。然而，我们发现了异质性的重要证据 我们的研究发现，我们大约90%的家庭与PAX3有关 区域。五个WS Type 2(WS2)家族中没有一个与PAX3连锁 候选区域，在一定距离内排除连锁(LOD&lt；-2.0) 17.5厘米。我们将标记D2S102定位到距PAX3不到1 cM的位置 位置(theta=0)，因此无法确定它是否映射 远端或近端，由于这两者之间缺乏交叉 记号笔。三个家系之一的减数分裂断裂点分析 WE1和PAX3之间的交叉提供了强有力的证据表明 这个家族的基因位于基因组的其他位置。

We performed linkage analyses and tests of locus heterogeneity of Waardenburg Syndrome (WS) using 9 DNA markers from 2q35-37, including two highly polymorphic microsatellites very closely linked to the candidate PAX3 locus. Analysis of 14 WS Type 1 (WS1) families at PAX3 yielded a maximum LOD score of 27.81, theta = .010, theta m = .007 assuming homogeneity. However, we found significant evidence of heterogeneity in our study, with approximately 90% of our families linked to the PAX3 region. None of five WS Type 2 (WS2) families showed linkage to the PAX3 candidate region, and linkage was excluded (LOD < -2.0) up to a distance of 17.5 cM. We localized the marker D2S102 to less than 1cM from PAX3 locus (theta = 0), and thus were unable to determine whether it mapped distally or proximally due to lack of crossovers between these two markers. Meiotic breakpoint analysis in one of the three families with a crossover between WE1 and PAX3 provides strong evidence that the disease gene in this family is located elsewhere in the genome.