Analysis of PKD1 for genomic deletion by multiplex ligation-dependent probe assay:: Absence of hot spots
Analysis of PKD1 for genomic deletion by multiplex ligation-dependent probe assay:: Absence of hot spots
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DOI：
10.1016/j.ygeno.2007.10.003
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发表时间：
2008-02-01
期刊：
影响因子：
4.4
通讯作者：
Kwiatkowski, David J.
中科院分区：
文献类型：
--
作者：
Kozlowski, Piotr;Bissler, John;Kwiatkowski, David J.
常染色体显性遗传性多囊肾病主要是由于PKD 1的突变。PKD 1具有不寻常的基因组结构，包括内含子2 - 1中的2.5-kb多聚嘧啶序列，这被假定为导致高比率的自发基因组突变事件。此外，大多数基因在基因组中的其他地方以97-99%的同一性重复三到六次。为了鉴定PKD 1的基因组突变，我们开发了一种多重连接依赖性探针测定（MLPA），其中PKD 1及其拷贝之间的变异位点位于MLPA探针组的连接位点。13个探针组覆盖PKD 1外显子2至46，平均间距为2.5 kb。对27例独立PKD患者样本的分析显示，没有证据表明基因组缺失局限于PKD。对15例TSC 2缺失延伸至PKD 1的结节性硬化症患者样本的分析显示，没有证据表明在多聚嘧啶道附近的断点聚集。(c)2007年爱思唯尔公司All rights reserved.
Autosomal dominant polycystic kidney disease is largely due to mutations in PKD1. PKD1 has an unusual genomic structure, including a 2.5-kb polypyrimidine sequence in intron 2 1, which has been postulated to lead to a high rate of spontaneous genomic mutation events. In addition, the majority of the gene is duplicated three to six times at 97-99% identity elsewhere in the genome. To identify genomic mutations in PKD1, we developed a multiplex ligation-dependent probe assay (MLPA) in which sites of variation between PKD1 and its copies were positioned at the ligation sites of the MLPA probe sets. Thirteen probe sets covered PKD1 exons 2 through 46, at an average spacing of 2.5 kb. Analysis of 27 independent PKD patient samples showed no evidence for genomic deletions confined to PKD]. Analysis of 15 tuberous sclerosis patient samples in which deletions in TSC2 extended into PKD1 showed no evidence of clustering of breakpoints near the polypyrimidine tract. (c) 2007 Elsevier Inc. All rights reserved.