Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing.
Rapid detection of expanded short tandem repeats in personal genomics using hybrid sequencing.
复制标题
使用混合测序快速检测个人基因组学中短串联重复序列。
DOI：
10.1093/bioinformatics/btt647
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发表时间：
2014-03-15
期刊：
影响因子：
--
通讯作者：
Morishita S
中科院分区：
文献类型：
--
作者：
Doi K;Monjo T;Hoang PH;Yoshimura J;Yurino H;Mitsui J;Ishiura H;Takahashi Y;Ichikawa Y;Goto J;Tsuji S;Morishita S
研究背景：短串联重复序列（STR），即2-6个核苷酸的DNA重复序列的长扩增与一些遗传疾病有关。具有成本效益的高通量测序可以快速产生数十亿个短读段，这对于发现疾病相关的STR非常有用。然而，在短读段中计数STR仍然在很大程度上未被探索，因为难以阐明远长于100 bp（短读段的典型长度）的STR。结果如下：我们建议从头开始的程序感测和定位长STR迅速使用的频率分布的所有STR和双端读取信息。我们使用生物学重复验证了该方法的可重复性，并使用它来定位与脑部疾病（SCA 31）相关的STR。随后，我们使用SMRTTM测序（Pacific Biosciences）对11个SCA 31样品中的该STR位点进行测序，以核苷酸分辨率确定2.3-3.1 kb序列，并揭示（TGGAA）-和（TAAAATAGAA）-重复扩增决定了与SCA 31相关的重复扩增的不稳定性。我们的方法也可以识别常见的STR，（AAAG）-和（AAAAG）-重复扩增，这是显着扩大在SCA 31样品中的四个位置。这是第一个提出的使用短和长读段的混合测序在个人基因组中快速发现疾病相关长STR的方法。可用性和实施：我们的TRhist软件可在http://trhist.gi.k.u-tokyo.ac.jp/上获得。联系方式：moris@cb.k.u-tokyo.ac.jp补充信息：补充数据可从生物信息学在线网站获得。
Motivation: Long expansions of short tandem repeats (STRs), i.e. DNA repeats of 2–6 nt, are associated with some genetic diseases. Cost-efficient high-throughput sequencing can quickly produce billions of short reads that would be useful for uncovering disease-associated STRs. However, enumerating STRs in short reads remains largely unexplored because of the difficulty in elucidating STRs much longer than 100 bp, the typical length of short reads. Results: We propose ab initio procedures for sensing and locating long STRs promptly by using the frequency distribution of all STRs and paired-end read information. We validated the reproducibility of this method using biological replicates and used it to locate an STR associated with a brain disease (SCA31). Subsequently, we sequenced this STR site in 11 SCA31 samples using SMRTTM sequencing (Pacific Biosciences), determined 2.3–3.1 kb sequences at nucleotide resolution and revealed that (TGGAA)- and (TAAAATAGAA)-repeat expansions determined the instability of the repeat expansions associated with SCA31. Our method could also identify common STRs, (AAAG)- and (AAAAG)-repeat expansions, which are remarkably expanded at four positions in an SCA31 sample. This is the first proposed method for rapidly finding disease-associated long STRs in personal genomes using hybrid sequencing of short and long reads. Availability and implementation: Our TRhist software is available at http://trhist.gi.k.u-tokyo.ac.jp/. Contact: moris@cb.k.u-tokyo.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online.
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影响因子：
64.8
作者：
Kong A;Frigge ML;Masson G;Besenbacher S;Sulem P;Magnusson G;Gudjonsson SA;Sigurdsson A;Jonasdottir A;Jonasdottir A;Wong WS;Sigurdsson G;Walters GB;Steinberg S;Helgason H;Thorleifsson G;Gudbjartsson DF;Helgason A;Magnusson OT;Thorsteinsdottir U;Stefansson K
通讯作者：
Stefansson K
影响因子：
56.9
作者：
KREMER, EJ;PRITCHARD, M;RICHARDS, RI
通讯作者：
RICHARDS, RI
影响因子：
64.8
作者：
LASPADA, AR;WILSON, EM;FISCHBECK, KH
通讯作者：
FISCHBECK, KH
影响因子：
--
作者：
MAIN, MG;LORENTZ, RJ
通讯作者：
LORENTZ, RJ
影响因子：
5.8
作者：
Mudunuri, Suresh B.;Nagarajaram, Hampapathalu A.
通讯作者：
Nagarajaram, Hampapathalu A.