NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome
NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome
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DOI：
10.1038/ng1363
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发表时间：
2004-06-01
期刊：
影响因子：
30.8
通讯作者：
Strachan, T
中科院分区：
文献类型：
--
作者：
Tonkin, ET;Wang, TJ;Strachan, T
Cornelia de Lange综合征（CdLS）是一种以面部畸形、智力迟钝、生长迟缓和肢体减少缺陷为特征的多发性畸形疾病（1,2）。我们鉴定并鉴定了一个在CdLS个体中突变的新基因NIPBL，并确定了其结构以及小鼠、大鼠和斑马鱼的同源基因结构。我们将其蛋白质产品命名为delangin。脊椎动物脱毛素与果蝇、蠕虫、植物和真菌中的同源物有很大的同源性，包括scc2型姐妹染色单体内聚蛋白和D. melanogaster Nipped-B。我们认为脱血管素功能紊乱可能不恰当地激活DLX基因，从而导致CdLS中近端肢体模式缺陷。基因组分析通常在二倍体动物和植物基因组中识别个体delangin或nipped - b样同源物。祖先姐妹染色单体内聚蛋白的进化在发育基因调控中获得了额外的作用，这表明CdLS和罗伯茨综合征之间存在相似之处。
Cornelia de Lange syndrome (CdLS) is a multiple malformation disorder characterized by dysmorphic facial features, mental retardation, growth delay and limb reduction defects(1,2). We indentified and characterized a new gene, NIPBL, that is mutated in individuals with CdLS and determined its structure and the structures of mouse, rat and zebrafish homologs. We named its protein product delangin. Vertebrate delangins have substantial homology to orthologs in flies, worms, plants and fungi, including Scc2-type sister chromatid cohesion proteins, and D. melanogaster Nipped-B. We propose that perturbed delangin function may inappropriately activate DLX genes, thereby contributing to the proximodistal limb patterning defects in CdLS. Genome analyses typically identify individual delangin or Nipped-B-like orthologs in diploid animal and plant genomes. The evolution of an ancestral sister chromatid cohesion protein to acquire an additional role in developmental gene regulation suggests that there are parallels between CdLS and Roberts syndrome.