Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.
Linkage of an autosomal dominant clefting syndrome (Van der Woude) to loci on chromosome Iq.
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发表时间：
1990-03
影响因子：
9.8
通讯作者：
J. C. Murray;D. Nishimura;K. Buetow;H. Ardinger;M. Spence;R. Sparkes;R. Falk;P. Falk;R. Gardner;E. Harkness;L. Glinski;R. Pauli;Yusuke Nakamura;P. Green;A. Schinzel
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文献类型：
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作者：
J. C. Murray;D. Nishimura;K. Buetow;H. Ardinger;M. Spence;R. Sparkes;R. Falk;P. Falk;R. Gardner;E. Harkness;L. Glinski;R. Pauli;Yusuke Nakamura;P. Green;A. Schinzel
货车德沃德综合征（VWS）是一种常染色体显性遗传疾病，其中受影响的个体具有以下一种或多种表现：唇裂、腭裂、缺牙或旁正中下唇凹陷。VWS是单基因异常干扰正常颅面形态发生的一个典型例子。作为鉴定参与人类发育的基因的第一步，我们使用候选基因和区域方法来寻找与VWS的联系。研究了6个有3代或3代以上受影响个体的家庭。1 q上的肾素（REN）基因和VWS之间存在连锁（θ = 0.02，lod评分= 9.09）的证据。其他连锁基因座包括CR 1、D1 S58和D1 S53。层粘连蛋白B2（LAMB 2），一种基底膜蛋白，和衰变加速因子（decay-accelerating factor）的基因作为可能的候选基因进行了研究。VWS与LAMB 2和LAMB 2之间的互补性排除了这些基因在本报告中研究的家族的VWS病因中的因果作用。多点连锁分析表明，VWS位点两侧的REN和D1 S65在lod值为10.83。这种与肾素和其他邻近位点的紧密连锁为确定这种人类发育障碍的分子异常提供了第一步。
Van der Woude syndrome (VWS) is an autosomal dominant disorder in which affected individuals have one or more of the following manifestations: cleft lip, cleft palate, hypodontia, or paramedian lower-lip pits. VWS is a well-characterized example of a single-gene abnormality that disturbs normal craniofacial morphogenesis. As a first step in identifying genes involved in human development, we used a candidate-gene-and-region approach to look for a linkage to VWS. Six families with 3 or more generations of affected individuals were studied. Evidence for linkage (theta = 0.02, lod score = 9.09) was found between the renin (REN) gene on 1q and VWS. Other linked loci included CR1, D1S58, and D1S53. The genes for laminin B2 (LAMB2), a basement-membrane protein, and for decay-accelerating factor (DAF) were studied as possible candidate genes on 1q. Recombinants between VWS and both LAMB2 and DAF excluded these genes from a causal role in the etiology of VWS for the families studied in this report. Multipoint linkage analysis indicated that the VWS locus was flanked by REN and D1S65 at a lod score of 10.83. This tight linkage with renin and other nearby loci provides a first step in identifying the molecular abnormality underlying this disturbance of human development.