Targeted Locus Amplification and Next-Generation Sequencing

Hottentot, Quint P; Min, Max van; Splinter, Erik; White, Stefan J.

doi:10.1007/978-1-4939-6442-0_13

Cited by 39 publications

(110 citation statements)

References 6 publications

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“…The BAC/PAC/cosmid vectors were included both to capture critical lines of interest and to test the feasibility of the TLA process on these larger constructs. A schematic of the TLA process, depicted in Figure 1C, was performed essentially as described ((de Vree et al 2014; Hottentot et al 2017); Materials and Methods) using primers specific for known elements of each transgenic line (Supplementary Table 1). Transgene insertion sites result in high sequencing coverage across the transgene and its insertion site(s), and at least one putative fusion read across the transgene-genome breakpoint was identified for all 40 lines (Table 1; Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…A prior report using FISH found that transgenes tend to insert into G-positve band regions (Nakanishi et al 2002), which typically have reduced gene density, but the mapped transgenes were not assessed for expression levels, so it is unclear if these data are representative of transgenes used in the wider scientific community. More recently, Targeted Locus Amplification (TLA) (de Vree et al 2014; Hottentot et al 2017) has been employed to identify the insertion site for 7 Cre driver lines(Cain-Hom et al 2017), only one of which was found to insert into an annotated gene. However, because of the small sample size, it is not clear if this rate of mutagenesis is representative of the genome-wide rates in larger collections representing a variety of transgene types.…”

Section: Introductionmentioning

confidence: 99%

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Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis

Goodwin

Splinter

Davis

et al. 2017

Preprint

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1Transgenesis has been a mainstay of mouse genetics for over 30 years, providing numerous models of 2 human disease and critical genetic tools in widespread use today. Generated through the random 3 integration of DNA fragments into the host genome, transgenesis can lead to insertional mutagenesis if a 4 coding gene or essential element is disrupted, and there is evidence that larger scale structural variation 5 can accompany the integration. The insertion sites of only a tiny fraction of the thousands of transgenic 6 lines in existence have been discovered and reported due in part to limitations in the discovery tools.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis

Goodwin

Splinter

Davis

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…Identified uncommon SNVs and indels. Identification of ApoE transgene locus, viral integration sites, and used to study chromosomal rearrangement for MLL gene TLA analysis pipeline details in [ 107 ] Targeted chromatin capture (T2C) [ 108 ] Provides affordable diagnostic tools with restriction enzyme resolution to understand domain and compartments at clinically relevant site. Can be applied to many regions of the genome simultaneously (many loci to all loci) Output limited to preselected regions.…”

Section: Approaches To Studying Disease and 3d Genome Architecturementioning

confidence: 99%

Three-dimensional genome architecture and emerging technologies: looping in disease

Mishra

Hawkins

2017

Genome Med

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Genome compaction is a universal feature of cells and has emerged as a global regulator of gene expression. Compaction is maintained by a multitude of architectural proteins, long non-coding RNAs (lncRNAs), and regulatory DNA. Each component comprises interlinked regulatory circuits that organize the genome in three-dimensional (3D) space to manage gene expression. In this review, we update the current state of 3D genome catalogues and focus on how recent technological advances in 3D genomics are leading to an enhanced understanding of disease mechanisms. We highlight the use of genome-wide chromatin conformation capture (Hi-C) coupled with oligonucleotide capture technology (capture Hi-C) to map interactions between gene promoters and distal regulatory elements such as enhancers that are enriched for disease variants from genome-wide association studies (GWASs). We discuss how aberrations in architectural units are associated with various pathological outcomes, and explore how recent advances in genome and epigenome editing show great promise for a systematic understanding of complex genetic disorders. Our growing understanding of 3D genome architecture-coupled with the ability to engineer changes in it-may create novel therapeutic opportunities.

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“…NGS can find an immunoglobulin-based MRD marker in the majority of patients, it can reach higher sensitivity levels and is a valid strategy to describe tumor clonal heterogeneity and evolution (80,81,94,95). In addition, other NGS-based techniques, such as targetedlocus amplification (TLA), can provide a newly identified, translocation-based MRD marker in patients without an IGH-derived molecular marker, and may help to perform MRD analysis on subsequent follow-up samples (96,97).…”

Section: Future Directions Of Mrd Studies: Novel Tools Tissues and mentioning

confidence: 99%

Personalized Medicine in Lymphoma: Tailoring Treatment According to Minimal Residual Disease

Dogliotti

Ferrero

2017

MRAJ

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Mature B-cell disorders have recently become highly curable diseases thanks to the introduction of new treatment strategies; nonetheless, despite evidence of complete remission, many patients affected by lymphoma or myeloma eventually relapse and need salvage therapy. Minimal residual disease (MRD) detection and quantification is a powerful tool to evaluate treatment efficacy, to stratify patients, and to predict long-term outcome. In fact, in the current landscape of novel, highly efficacious but toxic and often costly targeted therapies, early identification of factors predictive of treatment response or refractoriness is the key to avoid overtreatment of patients and thus also to reduce costs for health care system.In this article, we reviewed the prognostic role of MRD in follicular lymphoma, mantle cell lymphoma and multiple myeloma. We analyzed published clinical studies and available methodologies, and we described the major ongoing studies of MRD-driven tailored treatment in these diseases. Finally, we discussed novel applications and techniques for MRD identification in hematologic malignancies and future directions of MRD-oriented research. In particular, we hypothesized some possible, next-generation, precision medicine trials in lymphoproliferative diseases based on the most promising currently available biomarkers.

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Targeted Locus Amplification and Next-Generation Sequencing

Cited by 39 publications

References 6 publications

Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis

Large-scale discovery of mouse transgenic integration sites reveals frequent structural variation and insertional mutagenesis

Three-dimensional genome architecture and emerging technologies: looping in disease

Personalized Medicine in Lymphoma: Tailoring Treatment According to Minimal Residual Disease

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