scholarly journals Paired-end Mappability of Transposable Elements in the Human Genome

2019 ◽  
Author(s):  
Corinne E Sexton ◽  
Mira V Han
Keyword(s):  
Transposable Elements ◽  
Human Genome ◽  
Read Length ◽  
Sequencing Technology ◽  
Repetitive Nature ◽  
Specific Mapping ◽  
Conventional Sequencing

AbstractThough transposable elements make up around half of the human genome, the repetitive nature of their sequences makes it difficult to accurately align conventional sequencing reads. However, in light of new advances in sequencing technology, such as increased read length and paired-end libraries, these repetitive regions are now becoming easier to align to. This study investigates the mappability of transposable elements with 50bp, 76bp and 100bp paired-end read libraries. With respect to those read lengths and allowing for 3 mismatches during alignment, over 68%, 85%, and 88% of all transposable elements in the RepeatMasker database are uniquely mappable, suggesting that accurate locus-specific mapping of older transposable elements is well within reach.

scholarly journals CRISPR-mediated biocontainment

2020 ◽  
Author(s):  
Oscar Castanon ◽  
Cory J. Smith ◽  
Parastoo Khoshakhlagh ◽  
Raphael Ferreira ◽  
Marc Güell ◽  
...  
Keyword(s):  
Cell Death ◽  
Transposable Elements ◽  
Human Genome ◽  
Genome Editing ◽  
Copy Number ◽  
Proof Of Concept ◽  
Defense System ◽  
Dna Breaks ◽  
Repetitive Nature ◽  
Mammalian Genomes

AbstractWe have exploited the repetitive nature of transposable elements of the human genome to generate synthetic circuits. Transposable elements such as LINE-1 and Alu have successfully replicated in mammalian genomes throughout evolution to reach a copy number ranging from thousands to more than a million. Targeting these repetitive elements with programmable DNA nucleases such as CRISPR-Cas9 rapidly induce extremely high levels of cell death. We use this genotoxic feature to build synthetic biocontainment circuits: CRISPR defense system (CRISPR-DS) capable of preventing CRISPR genome editing, and we introduce the proof-of-concept of CRISPR Safety-Switch, an inducible, stringent and non-leaky kill-switch capable of clearing out cell lines resistant to DNA breaks.

scholarly journals Simultaneous TE Analysis of 19 Heliconiine Butterflies Yields Novel Insights into Rapid TE-Based Genome Diversification and Multiple SINE Births and Deaths

2019 ◽  
Vol 11 (8) ◽  
pp. 2162-2177 ◽  
Author(s):  
David A Ray ◽  
Jenna R Grimshaw ◽  
Michaela K Halsey ◽  
Jennifer M Korstian ◽  
Austin B Osmanski ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Common Ancestor ◽  
Genome Structure ◽  
Detailed Examination ◽  
Structure And Function ◽  
Evolutionary Processes ◽  
Repetitive Nature ◽  
Daunting Task ◽  
And Function

Abstract Transposable elements (TEs) play major roles in the evolution of genome structure and function. However, because of their repetitive nature, they are difficult to annotate and discovering the specific roles they may play in a lineage can be a daunting task. Heliconiine butterflies are models for the study of multiple evolutionary processes including phenotype evolution and hybridization. We attempted to determine how TEs may play a role in the diversification of genomes within this clade by performing a detailed examination of TE content and accumulation in 19 species whose genomes were recently sequenced. We found that TE content has diverged substantially and rapidly in the time since several subclades shared a common ancestor with each lineage harboring a unique TE repertoire. Several novel SINE lineages have been established that are restricted to a subset of species. Furthermore, the previously described SINE, Metulj, appears to have gone extinct in two subclades while expanding to significant numbers in others. This diversity in TE content and activity has the potential to impact how heliconiine butterflies continue to evolve and diverge.

scholarly journals Transposable elements that have recently been mobile in the human genome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Matias I. Autio ◽  
Talal Bin Amin ◽  
Arnaud Perrin ◽  
Jen Yi Wong ◽  
Roger S.-Y. Foo ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Human Genome ◽  
Genetic Disorders ◽  
Statistical Test ◽  
Population History ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Allele Specific ◽  
Regulatory Potential

Abstract Background Transposable elements (TE) comprise nearly half of the human genome and their insertions have profound effects to human genetic diversification and as well as disease. Despite their abovementioned significance, there is no consensus on the TE subfamilies that remain active in the human genome. In this study, we therefore developed a novel statistical test for recently mobile subfamilies (RMSs), based on patterns of overlap with > 100,000 polymorphic indels. Results Our analysis produced a catalogue of 20 high-confidence RMSs, which excludes many false positives in public databases. Intriguingly though, it includes HERV-K, an LTR subfamily previously thought to be extinct. The RMS catalogue is strongly enriched for contributions to germline genetic disorders (P = 1.1e-10), and thus constitutes a valuable resource for diagnosing disorders of unknown aetiology using targeted TE-insertion screens. Remarkably, RMSs are also highly enriched for somatic insertions in diverse cancers (P = 2.8e-17), thus indicating strong correlations between germline and somatic TE mobility. Using CRISPR/Cas9 deletion, we show that an RMS-derived polymorphic TE insertion increased the expression of RPL17, a gene associated with lower survival in liver cancer. More broadly, polymorphic TE insertions from RMSs were enriched near genes with allele-specific expression, suggesting widespread effects on gene regulation. Conclusions By using a novel statistical test we have defined a catalogue of 20 recently mobile transposable element subfamilies. We illustrate the gene regulatory potential of RMS-derived polymorphic TE insertions, using CRISPR/Cas9 deletion in vitro on a specific candidate, as well as by genome wide analysis of allele-specific expression. Our study presents novel insights into TE mobility and regulatory potential and provides a key resource for human disease genetics and population history studies.

scholarly journals Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

2019 ◽  
Author(s):  
Tamara Ovejero ◽  
Océane Sadones ◽  
Teresa Sánchez-Fito ◽  
Eloy Almenar-Pérez ◽  
José Andrés Espejo ◽  
...  
Keyword(s):  
Immune System ◽  
Transposable Elements ◽  
Immune Cells ◽  
Chronic Fatigue ◽  
Sequencing Technology ◽  
Fatigue Syndrome ◽  
Future Work ◽  
First Time ◽  
Herv Expression ◽  
Healthy Participants

The development of nucleic acid sequencing technology and the unprecedented availability of metadata has evidenced that 45% of human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically needed. Aberrant regulation of TEs, and of human retroviral endogenous sequences (HERVs) in particular, associates with several neurologic and autoimmune diseases, including the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) frequently comorbid with fibromyalgia (FM). However, no study has yet addressed whether abnormal expression of these sequences correlates with FM. The work presented here shows, for the first time, that in fact HERVs of the H, K and W types are overexpressed in the cells of the immune system of FM patients with or without comorbid ME/CFS. The patients with increased HERV expression (N=14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. In support of our proposal that TE activation is a contributor to FM, we find that the tRNA pools are decreased in comparison to matched healthy participants (N=14). The findings reported here could explain the flu-like symptoms FM patients present with in the absence of concomitant infections. Future work towards identifying specific genomic loci differentially affected in FM and ME/CFS is granted.

scholarly journals Current and Future Methodology for Quantitation and Site-specific Mapping the Location of DNA Adducts

2021 ◽  
Author(s):  
Gunnar Boysen ◽  
Intawat Nookaew
Keyword(s):  
Dna Sequencing ◽  
Dna Adducts ◽  
Single Molecule ◽  
State Of The Art ◽  
Dna Adduct ◽  
Sequencing Technology ◽  
Specific Mass ◽  
Comprehensive Picture ◽  
Specific Mapping ◽  
Altered Gene

Abstract: Formation of DNA adducts is a key event for a genotoxic mode of action and its formation is often use as surrogate for mutation and cancer. Interest in DNA adducts are twofold, first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. High chemically specific mass spectrometry methods have been established for DNA adduct quantitation and elegant bio-analytic methods utilizing enzymes, various chemistries, and molecular biology methods to visualize the location of DNA adducts. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. We will briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technology that is expected to achieve both measures simultaneously. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation.

scholarly journals Cultivating DNA Sequencing Technology After the Human Genome Project

2020 ◽  
Vol 21 (1) ◽  
pp. 117-138
Author(s):  
Jeffery A. Schloss ◽  
Richard A. Gibbs ◽  
Vinod B. Makhijani ◽  
Andre Marziali
Keyword(s):  
Dna Sequencing ◽  
Human Genome ◽  
Human Genome Project ◽  
Technology Development ◽  
Genome Project ◽  
Alternative Methods ◽  
Biological Research ◽  
Sequencing Technology ◽  
Core Technology ◽  
The Human Genome Project

When the Human Genome Project was completed in 2003, automated Sanger DNA sequencing with fluorescent dye labels was the dominant technology. Several nascent alternative methods based on older ideas that had not been fully developed were the focus of technical researchers and companies. Funding agencies recognized the dynamic nature of technology development and that, beyond the Human Genome Project, there were growing opportunities to deploy DNA sequencing in biological research. Consequently, the National Human Genome Research Institute of the National Institutes of Health created a program—widely known as the Advanced Sequencing Technology Program—that stimulated all stages of development of new DNA sequencing methods, from innovation to advanced manufacturing and production testing, with the goal of reducing the cost of sequencing a human genome first to $100,000 and then to $1,000. The events of this period provide a powerful example of how judicious funding of academic and commercial partners can rapidly advance core technology developments that lead to profound advances across the scientific landscape.

The Roles of Long Non-coding RNA in Osteoporosis

2020 ◽  
Vol 15 (7) ◽  
pp. 639-645 ◽  
Author(s):  
Ying Li ◽  
Jinglan Li ◽  
Leilei Chen ◽  
Liangliang Xu
Keyword(s):  
Human Genome ◽  
Protein Modification ◽  
High Throughput Sequencing ◽  
Genome Project ◽  
Sequencing Technology ◽  
Non Coding Rna ◽  
Transcription Process ◽  
Brittle Fractures ◽  
The Human Genome Project ◽  
Long Non Coding Rna

The Human Genome Project (HGP) announced in 2001 that it had sequenced the entire human genome, yielding nearly complete human DNA. About 98.5 percent of the human genome has been found to be non-coding sequences. Long non-coding RNA (lncRNA) is a non-coding RNA with a length between 200 and 100,000 nucleotide units. Because of shallow research on lncRNA, it was believed that it had no biological functions, but exists as a by-product of the transcription process. With the development of high-throughput sequencing technology, studies have shown that lncRNA plays important roles in many processes by participating in epigenetics, transcription, translation and protein modification. Current researches have shown that lncRNA also has an important part in the pathogenesis of osteoporosis. Osteoporosis is a common disorder of bone metabolism, also a major medical and socioeconomic challenge worldwide. It is characterized by a systemic reduction in bone mass and microstructure changes, which increases the risk of brittle fractures. It is more common in postmenopausal women and elderly men. However, the roles of lncRNA and relevant mechanisms in osteoporosis remain unclear. Based on this background, we hereby review the roles of lncRNA in osteoporosis, and how it influences the functions of osteoblasts and osteoclasts, providing reference to clinical diagnosis, treatment and prognosis of osteoporosis.

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