Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization.
Detection and Confirmation of Deafness-Causing Copy Number Variations in the STRC Gene by Massively Parallel Sequencing and Comparative Genomic Hybridization.
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DOI：
10.1177/0003489416661345
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Usami SI
中科院分区：
文献类型：
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作者：
Moteki H;Azaiez H;Sloan-Heggen CM;Booth K;Nishio SY;Wakui K;Yamaguchi T;Kolbe DL;Iwasa YI;Shearer AE;Fukushima Y;Smith RJ;Usami SI
拷贝数变异 (CNV) 是遗传性听力损失的主要原因，最常见的是位于 chr15q15.3 上的 STRC 基因，与 DFNB16 位点的常染色体隐性非综合征性听力损失 (ARNSHL) 存在因果关系。由于存在几乎相同的假基因 pSTRC，该假基因促进该基因组区域中复杂的基因组重排，因此对 STRC 序列数据的解释可能具有挑战性。通过大规模并行测序（TGE+MPS）进行靶向基因组富集已成为为听力损失提供全面基因检测的首选方法。我们的目的是使用已建立且经过验证的生物信息学方法来识别 STRC 区域中的 CNV。我们使用 TGE+MPS 来确定听力损失的遗传原因。 CNV 结果通过定制阵列比较基因组杂交（阵列 CGH）得到证实。在 40 名 ARNSHL 受试者中发现了 3 名患有进行性轻度至中度听力损失的先证者，以分离纯合 STRC 缺失和基因到假基因的转换。阵列 CGH 显示，删除/转换跨越 TGE+MPS 捕获的外显子之外的多个基因。这些数据进一步验证了在遗传性听力损失的临床诊断中整合简单变异变化和复杂基因组重排检测的必要性。
Copy number variations (CNVs), a major cause of genetic hearing loss, most frequently involve the STRC gene, located on chr15q15.3 and causally related to autosomal recessive non-syndromic hearing loss (ARNSHL) at the DFNB16 locus. The interpretation of STRC sequence data can be challenging due to the existence of a virtually identical pseudogene, pSTRC that promotes complex genomic rearrangements in this genomic region. Targeted genomic enrichment with massively parallel sequencing (TGE+MPS) has emerged as the preferred method by which to provide comprehensive genetic testing for hearing loss. We aimed to identify CNVs in the STRC region using established and validated bioinformatics methods. We used TGE+MPS to identify the genetic cause of hearing loss. CNV results were confirmed with customized array comparative genomic hybridization (array CGH). Three probands with progressive mild-to-moderate hearing loss were found among 40 subjects with ARNSHL to segregate homozygous STRC deletions and gene to pseudogene conversion. Array CGH showed that the deletions/conversions span multiple genes outside of the exons captured by TGE+MPS. These data further validate the necessity to integrate the detection of both simple variant changes and complex genomic rearrangements in the clinical diagnosis of genetic hearing loss.
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影响因子：
1.3
作者：
Hoppman N;Aypar U;Brodersen P;Brown N;Wilson J;Babovic-Vuksanovic D
通讯作者：
Babovic-Vuksanovic D
全基因组SNP基因分型鉴定立体纤维蛋白（Strc）基因是小儿双边感觉神经性听力障碍的主要因素。
影响因子：
2
作者：
Francey, Lauren J.;Conlin, Laura K.;Kadesch, Hanna E.;Clark, Dinah;Berrodin, Donna;Sun, Yi;Glessner, Joe;Hakonarson, Hakon;Jalas, Chaim;Landau, Chaim;Spinner, Nancy B.;Kenna, Margaret;Sagi, Michal;Rehm, Heidi L.;Krantz, Ian D.
通讯作者：
Krantz, Ian D.
影响因子：
4.4
作者：
Nord AS;Lee M;King MC;Walsh T
通讯作者：
Walsh T
影响因子：
4
作者：
Knijnenburg, J.;Oberstein, S. A. J. Lesnik;Szuhai, K.
通讯作者：
Szuhai, K.
影响因子：
64.8
作者：
通讯作者：
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