SVDetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data

Zeitouni, Bruno; Boeva, Valentina; Janoueix‐Lerosey, Isabelle; Loeillet, Sophie; Legoix-Né, Patricia; Nicolas, Alain; Delattre, Olivier; Barillot, Emmanuel

doi:10.1093/bioinformatics/btq293

Cited by 180 publications

(173 citation statements)

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“…Discordant reads were extracted and structural variations were identified using SVDetect. 25 The results allowed us to design primers for breakpoint spanning PCRs. In brief, genomic sequences flanking each of the breakpoints indicated by mate-pair analysis were extracted and masked for repetitive sequences using the UCSC Genomic Browser.…”

Section: Molecular Characterization Of Breakpoints Identified By Nextmentioning

confidence: 99%

Partial USH2A deletions contribute to Usher syndrome in Denmark

et al. 2015

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Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment, progressive visual loss owing to retinitis pigmentosa and in some cases vestibular dysfunction. Usher syndrome is divided into three subtypes, USH1, USH2 and USH3. Twelve loci and eleven genes have so far been identified. Duplications and deletions in PCDH15 and USH2A that lead to USH1 and USH2, respectively, have previously been identified in patients from United Kingdom, Spain and Italy. In this study, we investigate the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark using multiplex ligation-dependent probe amplification (MLPA). Two heterozygous deletions were identified in USH2A, but no deletions or duplications were identified in PCDH15. Next-generation mate-pair sequencing was used to identify the exact breakpoints of the two deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.

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Section: Molecular Characterization Of Breakpoints Identified By Nextmentioning

confidence: 99%

Partial USH2A deletions contribute to Usher syndrome in Denmark

et al. 2015

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“…The most basic algorithm is that applied by Breakdancer[77], Breakway[78], SVDetect[79], BreakSeq[80] and GASV[81]. These programs use mapping distance data provided through the paired-end alignment statistics to estimate the average fragment size of the library.…”

Section: Massively Parallel Sequencingmentioning

confidence: 99%

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Gundry

Vijg

2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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DNA mutations are the source of genetic variation within populations. The majority of mutations with observable effects are deleterious. In humans mutations in the germ line can cause genetic disease. In somatic cells multiple rounds of mutations and selection lead to cancer. The study of genetic variation has progressed rapidly since the completion of the draft sequence of the human genome. Recent advances in sequencing technology, most importantly the introduction of massively parallel sequencing (MPS), have resulted in more than a hundred-fold reduction in the time and cost required for sequencing nucleic acids. These improvements have greatly expanded the use of sequencing as a practical tool for mutation analysis. While in the past the high cost of sequencing limited mutation analysis to selectable markers or small forward mutation targets assumed to be representative for the genome overall, current platforms allow whole genome sequencing for less than $5,000. This has already given rise to direct estimates of germline mutation rates in multiple organisms including humans by comparing whole genome sequences between parents and offspring. Here we present a brief history of the field of mutation research, with a focus on classical tools for the measurement of mutation rates. We then review MPS, how it is currently applied and the new insight into human and animal mutation frequencies and spectra that has been obtained from whole genome sequencing. While great progress has been made, we note that the single most important limitation of current MPS approaches for mutation analysis is the inability to address low-abundance mutations that turn somatic tissues into mosaics of cells. Such mutations are at the basis of intra-tumor heterogeneity, with important implications for clinical diagnosis, and could also contribute to somatic diseases other than cancer, including aging. Some possible approaches to gain access to low-abundance mutations are discussed, with a brief overview of new sequencing platforms that are currently waiting in the wings to advance this exploding field even further.

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“…There are many methods for detecting SNPs (11)(12)(13)(14) and structural variants (SVs) (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), including NGS, which can capture nearly all DNA polymorphisms (26)(27)(28). This approach has been widely used to analyze markers in crop species such as rice (29), genes associated with diseases (6,26), and meiotic recombination in yeast and plants (30,31).…”

mentioning

confidence: 99%

Detection of genomic variations and DNA polymorphisms and impact on analysis of meiotic recombination and genetic mapping

Chen

Copenhaver

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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DNA polymorphisms are important markers in genetic analyses and are increasingly detected by using genome resequencing. However, the presence of repetitive sequences and structural variants can lead to false positives in the identification of polymorphic alleles. Here, we describe an analysis strategy that minimizes false positives in allelic detection and present analyses of recently published resequencing data from Arabidopsis meiotic products and individual humans. Our analysis enables the accurate detection of sequencing errors, small insertions and deletions (indels), and structural variants, including large reciprocal indels and copy number variants, from comparisons between the resequenced and reference genomes. We offer an alternative interpretation of the sequencing data of meiotic products, including the number and type of recombination events, to illustrate the potential for mistakes in single-nucleotide polymorphism calling. Using these examples, we propose that the detection of DNA polymorphisms using resequencing data needs to account for nonallelic homologous sequences. Fig. 1 A and B). They can have phenotypic consequences and also serve as molecular markers for genetic analyses, facilitating linkage and association studies of genetic diseases, and other traits in humans (4-6), animals, plants, (7)(8)(9)(10) and other organisms. Using DNA polymorphisms for modern genetic applications requires low-error, high-throughput analytical strategies. Here, we illustrate the use of short-read nextgeneration sequencing (NGS) data to detect DNA polymorphisms in the context of whole-genome analysis of meiotic products.There are many methods for detecting SNPs (11-14) and structural variants (SVs) (15-25), including NGS, which can capture nearly all DNA polymorphisms (26-28). This approach has been widely used to analyze markers in crop species such as rice (29), genes associated with diseases (6, 26), and meiotic recombination in yeast and plants (30,31). However, accurate identification of DNA polymorphisms can be challenging, in part because short-read sequencing data have limited information for inferring chromosomal context.Genomes usually contain repetitive sequences that can differ in copy number between individuals (26-28, 31); therefore, resequencing analyses must account for chromosomal context to avoid mistaking highly similar paralogous sequences for polymorphisms. Here, we use recently published datasets to describe several DNA sequence features that can be mistaken as allelic (32, 33) and describe a strategy for differentiating between repetitive sequences and polymorphic alleles. We illustrate the effectiveness of these analyses by examining the reported polymorphisms from the published datasets.Meiotic recombination is initiated by DNA double-strand breaks (DSBs) catalyzed by the topoisomerase-like SPORULATION 11 (SPO11). DSBs are repaired as either crossovers (COs) between chromosomes (Fig. 1C), or noncrossovers (NCOs). Both COs and NCOs can be accompanied by gene conversion (GC) events, whic...

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SVDetect: a tool to identify genomic structural variations from paired-end and mate-pair sequencing data

Cited by 180 publications

References 6 publications

Partial USH2A deletions contribute to Usher syndrome in Denmark

Partial USH2A deletions contribute to Usher syndrome in Denmark

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Detection of genomic variations and DNA polymorphisms and impact on analysis of meiotic recombination and genetic mapping

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