Next‐generation sequencing as a tool for breakpoint analysis in rearrangements of the globin gene clusters

Clark, Barnaby; Shooter, Claire; Smith, Frances; Brawand, David; Thein, Swee Lay

doi:10.1111/ijlh.12680

Cited by 24 publications

(15 citation statements)

References 34 publications

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“…Most of the studies have been unable to verify the precise breakpoints due to previous technical limits. Our findings, and those from other studies (Hu et al , ; Clark et al , ), have proved that combinations of MLPA, array comparative genomic hybridization (array CGH) and NGS assays are very useful for identifying the known or unknown rearrangements in α‐ or β‐globin gene clusters. This duplication not only widens the spectrum of CNVs in globin genes but it is also the first report of a de novo large duplication, although some de novo point mutations have previously been found at this locus (Shang & Xu, ).…”

Section: Resultssupporting

confidence: 78%

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

et al. 2019

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Summary Next generation sequencing identified a de novo, 204 kb, tandem duplication (αααα204) in the α‐globin gene cluster of a Chinese thalassaemia intermedia patient. Haplotype analysis showed that the duplicated chromosome was of paternal origin. Molecular analysis of genomic DNA from the patient's lymphocytes, hair follicles, buccal mucosa cells, his father's lymphocytes and sperm cells excluded the possibility of somatic or germinal mosaicism. The analysis also indicated that this duplication arose during spermatogenesis. The microhomology in the breakpoint was found and suggested that this duplication could be formed by a coupled homologous and non‐homologous recombination mechanism.

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Section: Resultssupporting

confidence: 78%

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

et al. 2019

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“…Sorting and coordination of the mapped reads were illustrated using Integrative Genomics Viewer (IGV; https://software.broadinstitute.org/software/igv/) and split reads were analyzed (Clark, Shooter, Smith, Brawand, & Thein, 2017), as previously described (Imaizumi, Yamamoto‐Shimojima, Yanagishita, Ondo, Nishi, et al, 2020; Imaizumi, Yamamoto‐Shimojima, Yanagishita, Ondo, & Yamamoto, 2020). We identified soft‐clipped reads in the vicinity of the breakpoint based on the results of aCGH and FISH.…”

Section: Methodsmentioning

confidence: 99%

Breakpoint junction analysis for complex genomic rearrangements with the caldera volcano‐like pattern

et al. 2020

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Chromosomal triplications can be classified into recurrent and nonrecurrent triplications. Most of the nonrecurrent triplications are embedded in duplicated segments, and duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) has been established as one of the mechanisms of triplication. This study aimed to reveal the underlying mechanism of the TRP-DUP-TRP pattern of chromosomal aberrations, in which the appearance of moving averages obtained through array-based comparative genomic hybridization analysis is similar to the shadows of the caldera volcano-like pattern, which were first identified in two patients with neurodevelopmental disabilities. For this purpose, whole-genome sequencing using long-read Nanopore sequencing was carried out to confirm breakpoint junctions. Custom array analysis and Sanger sequencing were also used to detect all breakpoint junctions. As a result, the TRP-DUP-TRP pattern consisted of only two patterns of breakpoint junctions in both patients. In patient 1, microhomologies were identified in breakpoint junctions. In patient 2, more complex architectures with insertional segments were identified. Thus, replication-based mechanisms were considered as a mechanism of the TRP-DUP-TRP pattern.

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“…99 Another recent study focused on the detection of SVs as a cause of hemoglobinopathies. 100 The authors developed an automated analytical pipeline (Snappy) to detect the first duplication of the entire β globin cluster. The analysis method incorporated the assessment of sequence coverage and detection of split and discordant reads in an approach that could be applied to a routine diagnostic pathway.…”

Section: Next-generation Sequencing In Thrombosis and Hemostasismentioning

confidence: 99%

“…The analysis method incorporated the assessment of sequence coverage and detection of split and discordant reads in an approach that could be applied to a routine diagnostic pathway. 100 Finally, an ongoing study that shows great promise is the My Life Our Future (MLOF) program, which was initiated in 2012 to provide genetic analysis and expand hemophilia research by creating a research repository. 101 DNA from 5,141 MLOF subjects has undergone WGS through the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine program of the National Institutes of Health and will provide a large, comprehensive database that will serve as a valuable resource to study this disease in the future.…”

Section: Next-generation Sequencing In Thrombosis and Hemostasismentioning

confidence: 99%

Next-Generation Sequencing and Emerging Technologies

Kumar

Cowley

Davis

2019

Semin Thromb Hemost

204

160

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Genetic sequencing technologies are evolving at a rapid pace with major implications for research and clinical practice. In this review, the authors provide an updated overview of next-generation sequencing (NGS) and emerging methodologies. NGS has tremendously improved sequencing output while being more time and cost-efficient in comparison to Sanger sequencing. The authors describe short-read sequencing approaches, such as sequencing by synthesis, ion semiconductor sequencing, and nanoball sequencing. Third-generation long-read sequencing now promises to overcome many of the limitations of short-read sequencing, such as the ability to reliably resolve repeat sequences and large genomic rearrangements. By combining complementary methods with massively parallel DNA sequencing, a greater insight into the biological context of disease mechanisms is now possible. Emerging methodologies, such as advances in nanopore technology, in situ nucleic acid sequencing, and microscopy-based sequencing, will continue the rapid evolution of this area. These new technologies hold many potential applications for hematological disorders, with the promise of precision and personalized medical care in the future.

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Next‐generation sequencing as a tool for breakpoint analysis in rearrangements of the globin gene clusters

Abstract: Introduction: Next-generation sequencing (NGS), now embedded within genomic

Cited by 24 publications

References 34 publications

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

Breakpoint junction analysis for complex genomic rearrangements with the caldera volcano‐like pattern

Next-Generation Sequencing and Emerging Technologies

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