通过对一个视网膜色素变性家族进行靶向自适应纳米孔测序,确定 RP1 基因中 LINE-1 插入的特征

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Michael P. Backlund, Pauliina Repo, Harri Kangas, Kati Donner, Eeva-Marja Sankila, Julia Krootila, Maarjaliis Paavo, Kirmo Wartiovaara, Tero T. Kivelä, Joni A. Turunen
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引用次数: 0

摘要

视网膜色素变性(RP)是一组遗传性退行性视网膜疾病,影响着全球 150 多万人。在 30-50% 的视网膜色素变性患者中,目前的临床诊断基因面板仍无法确定其遗传原因。其原因可能是新型 RP 相关基因或非编码调控区的变异,或者是复杂的基因改变,如大结构变异。长线程测序技术的最新发展为高效分析复杂的基因变异提供了机会。我们对一个芬兰家族进行了分析,该家族三代共六人患有显性遗传的 RP。两名患者接受了全面的临床检查和临床诊断基因检测,随后在我们的实验室进行了全外显子测序。他们表现出 RP 的典型症状,但初步序列分析并未发现致病变异。对测序数据的重新分析发现,在RP1轴突微管相关(RP1)基因的第4外显子中插入了一个大小未知的LINE-1(L1)反转座子。通过对 RP1 基因进行靶向自适应纳米孔测序,进一步确定了与疾病分离的大型嵌合 L1 插入物的特征,从而确定 RP1 基因中的 5.6 kb L1 转座子插入物是这个显性遗传 RP 家族的病因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Characterisation of a LINE-1 Insertion in the RP1 Gene by Targeted Adaptive Nanopore Sequencing in a Family with Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a group of inherited degenerative retinal disorders affecting more than 1.5 million people worldwide. For 30-50% of individuals with RP, the genetic cause remains unresolved by current clinical diagnostic gene panels. It is likely explained by variants in novel RP-associated genes or noncoding regulatory regions, or by complex genetic alterations such as large structural variants. Recent developments in long-read sequencing techniques have opened an opportunity for efficient analysis of complex genetic variants. We analysed a Finnish family with dominantly inherited RP affecting six individuals in three generations. Two affected individuals underwent a comprehensive clinical examination in combination with a clinical diagnostic gene panel, followed by whole exome sequencing in our laboratory. They exhibited typical signs of RP, yet initial sequence analysis found no causative variants. Reanalysis of the sequencing data detected a LINE-1 (L1) retrotransposon insertion of unknown size in exon 4 of the RP1 axonemal microtubule-associated (RP1) gene. The large chimeric L1 insertion that segregated with the disease was further characterised using targeted adaptive nanopore sequencing of RP1, allowing us to identify a 5.6 kb L1 transposable element insertion in RP1 as the cause of RP in this family with dominantly inherited RP.

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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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