A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region
A transcript map of the newly defined 165 kb Wolf-Hirschhorn syndrome critical region
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DOI：
10.1093/hmg/6.2.317
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发表时间：
1997-02-01
影响因子：
3.5
通讯作者：
Altherr, MR
中科院分区：
文献类型：
--
作者：
Wright, TJ;Ricke, DO;Altherr, MR
Wolf-Hirschhorn综合征（WHS）是一种多发性畸形综合征，其特征是由于一条4号染色体短臂（4p16.3）的一段缺失而导致的精神和发育缺陷。由于这种疾病的复杂和可变的表达，WHS被认为是一种连续的基因综合征，其具有不确定数量的基因，这些基因对表型有贡献。为了鉴定有助于人类发育的基因以及其缺失导致这种综合征的基因，我们利用了一系列具有里程碑意义的cosmetics来鉴定WHS患者来源的细胞系的集合。用这些互补序列进行荧光原位杂交，将WHS关键区（WHSCR）精确到260 kb，该区域的基因组序列是可用的，并且通过BLAST分析该序列在dbEST数据库中检测到几个cDNA克隆，总共9个独立的cDNA及其预测的翻译产物，从该分析中显示与DNA或蛋白质数据库的成员没有显著的相似性，此外，这些基因已经定位在WHS关键区域内，并揭示了一种有趣的转录组织模式。先前发表的关于近端4 β-综合征患者的报道进一步将WHSCR细化到由基因座D4 S166和D453327定义的165 kb。这项工作提供了一个起点，了解多个基因或其他机制如何有助于与沃尔夫-赫希霍恩综合征相关的复杂表型。
Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome characterised by mental and developmental defects resulting from the absence of a segment of one chromosome 4 short arm (4p16.3). Due to the complex and variable expression of this disorder, it is thought that the WHS is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype, In an effort to identify genes that contribute to human development and whose absence results in this syndrome, we have utilised a series of landmark cosmids to characterise a collection of WHS patient derived cell lines. Fluorescence in situ hybridisation with these cosmids was used to refine the WHS critical region (WHSCR) to 260 kb, The genomic sequence of this region is available and analysis of this sequence through BLAST detected several cDNA clones in the dbEST data base, A total of nine independent cDNAs, and their predicted translation products, from this analysis Show no significant similarity to members of DNA or protein databases, Furthermore, these genes have been localised within the WHS critical region and reveal an interesting pattern of transcriptional organisation, A previously published report of a patient with proximal 4p- syndrome further refines the WHSCR to 165 kb defined by the loci D4S166 and D453327. This work provides the starting point to understand how multiple genes or other mechanisms can contribute to the complex phenotype associated with the Wolf-Hirschhorn syndrome.