In Silico identification of a common mobile element insertion in exon 4 of RP1.
In Silico identification of a common mobile element insertion in exon 4 of RP1.
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DOI：
10.1038/s41598-021-92834-4
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发表时间：
2021-06-28
影响因子：
4.6
通讯作者：
Han J
中科院分区：
文献类型：
--
作者：
Won D;Hwang JY;Shim Y;Byeon SH;Lee J;Lee CS;Kim M;Lim HT;Choi JR;Lee ST;Han J
移动元件插入（MEIs）通常超过短读测序技术的读取长度，因此经常被遗漏。最近，通过PCR和凝胶电泳在日本黄斑营养不良患者的RP1外显子4中检测到一个创始人Alu插入。我们的目标是开发一个grep搜索程序，用于使用未处理的短读取检测RP1外显子4中的Alu插入。在494名无亲缘关系的韩国遗传性眼病患者中，选择273名具有特定视网膜表型的患者，这些患者之前通过靶向面板或全外显子组测序进行了基因分型。五个先证有一个单一的杂合截断RP1变体，他们的一个未受影响的父母也携带这种变体。为了寻找隐藏的遗传变异，对2例患者进行了全基因组测序，结果显示AluY c.4052_4053ins328/p。（Tyr1352Alafs*9）在RP1外显子4中的插入。另外3个家族也发现了该aly插入，经PCR和凝胶电泳证实。我们开发了简化的grep搜索程序来检测RP1外显子4中的AluY插入。简单grep搜索结果显示，变异等位基因频率中位数为0.282（四分位数范围为0.232 ~ 0.383），120个对照样本无假阳性结果。RP1外显子4的MEI是韩国人常见的始创突变，发生率为1.8%。RP1-Alu grep程序有效地检测AluY插入，无需预处理原始数据或复杂的安装过程。
Mobile element insertions (MEIs) typically exceed the read lengths of short-read sequencing technologies and are therefore frequently missed. Recently, a founder Alu insertion in exon 4 of RP1 has been detected in Japanese patients with macular dystrophy by PCR and gel electrophoresis. We aimed to develop a grep search program for the detection of the Alu insertion in exon 4 of RP1 using unprocessed short reads. Among 494 unrelated Korean patients with inherited eye diseases, 273 patients with specific retinal phenotypes who were previously genotyped by targeted panel or whole exome sequencing were selected. Five probands had a single heterozygous truncating RP1 variant, and one of their unaffected parents also carry this variant. To find a hidden genetic variant, whole genome sequencing was performed in two patients, and it revealed AluY c.4052_4053ins328/p.(Tyr1352Alafs*9) insertion in RP1 exon 4. This AluY insertion was additionally identified in other 3 families, which was confirmed by PCR and gel electrophoresis. We developed simplified grep search program to detect this AluY insertion in RP1 exon 4. The simple grep search revealed a median variant allele frequency of 0.282 (interquartile range, 0.232–0.383), with no false-positive results using 120 control samples. The MEI in RP1 exon 4 was a common founder mutation in Korean, occurring in 1.8% of our cohort. The RP1-Alu grep program efficiently detected the AluY insertion, without the preprocessing of raw data or complex installation processes.
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影响因子：
7
作者：
Gardner EJ;Lam VK;Harris DN;Chuang NT;Scott EC;Pittard WS;Mills RE;1000 Genomes Project Consortium;Devine SE
通讯作者：
Devine SE
影响因子：
14.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
Comander J
影响因子：
16.6
作者：
Gardner, Eugene J.;Prigmore, Elena;Hurles, Matthew E.
通讯作者：
Hurles, Matthew E.
影响因子：
2.9
作者：
Hitti-Malin, Rebekkah J.;Burmeister, Louise M.;Mellersh, Cathryn S.
通讯作者：
Mellersh, Cathryn S.