Role of Transposable Elements in Genome Stability: Implications for Health and Disease DOI Open Access
Audesh Bhat, Trupti Ghatage,

Sonali Bhan

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7802 - 7802

Published: July 15, 2022

Most living organisms have in their genome a sizable proportion of DNA sequences capable mobilization; these are commonly referred to as transposons, transposable elements (TEs), or jumping genes. Although long thought no biological significance, advances sequencing and analytical technologies enabled precise characterization TEs confirmed ubiquitous presence across all forms life. These findings ignited intense debates over significance. The available evidence now supports the notion that exert major influence many aspects organismal Transposable contribute significantly evolution by giving rise genetic variations both active passive modes. Due intrinsic nature mobility within genome, primarily cause gene disruption large-scale genomic alterations including inversions, deletions, duplications. Besides instability, growing also points physiologically important functions TEs, such regulation through cis-acting control modulation transcriptome epigenetic control. In this review, we discuss latest demonstrating impact on stability underling mechanisms, those developed mitigate deleterious human health. We highlighted potential therapeutic application TEs.

Language: Английский

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil DOI Creative Commons
Michel Satya Naslavsky, Marília O. Scliar, Guilherme Lopes Yamamoto

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 4, 2022

Abstract As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly elderly Brazilians from census-based cohort, providing over 76 million variants, which ~2 absent large public databases. enables identification ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb genomic segments human genome reference, 140 alleles HLA genes resources. We reclassify curate pathogenicity assertions four hundred variants in associated with dominantly-inherited Mendelian disorders calculate incidence selected recessive disorders, demonstrating clinical usefulness study. Finally, observe that imputation could be significantly improved compared to available datasets since rare variation represents largest proportion input WGS. These results demonstrate even smaller sample sizes underrepresented populations bring relevant studies, especially when exploring analyses allowed only by

Language: Английский

Citations

88
Repetitive DNA sequence detection and its role in the human genome DOI Creative Commons
Xingyu Liao,

Wufei Zhu,

Juexiao Zhou

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Sept. 19, 2023

Abstract Repetitive DNA sequences playing critical roles in driving evolution, inducing variation, and regulating gene expression. In this review, we summarized the definition, arrangement, structural characteristics of repeats. Besides, introduced diverse biological functions repeats reviewed existing methods for automatic repeat detection, classification, masking. Finally, analyzed type, structure, regulation human genome their role induction complex diseases. We believe that review will facilitate a comprehensive understanding provide guidance annotation in-depth exploration its association with

Language: Английский

Citations

65
LINE-1 transcription activates long-range gene expression DOI
Xiufeng Li,

Luyao Bie,

Yang Wang

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(7), P. 1494 - 1502

Published: June 7, 2024

Language: Английский

Citations

21
Therapeutic targeting of DNA methylation alterations in cancer DOI

Abigail V. Lee,

Kevin Nestler, Katherine B. Chiappinelli

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 258, P. 108640 - 108640

Published: April 1, 2024

Language: Английский

Citations

19
Transposable Elements: A Common Feature of Neurodevelopmental and Neurodegenerative Disorders DOI Open Access
Marie E. Jönsson, Raquel Garza, Pia A. Johansson

et al.

Trends in Genetics, Journal Year: 2020, Volume and Issue: 36(8), P. 610 - 623

Published: June 1, 2020

Language: Английский

Citations

91
State of the art of bacterial chemotaxis DOI
Richa Karmakar

Journal of Basic Microbiology, Journal Year: 2021, Volume and Issue: 61(5), P. 366 - 379

Published: March 9, 2021

Bacterial chemotaxis is a biased movement of bacteria toward the beneficial chemical gradient or away from toxic gradient. This achieved by sensing chemoreceptors. In most studies, Escherichia coli has been used as model organism. E. have about 4-6 flagella on their surfaces, and motility rotating flagella. Each flagellum reversible flagellar motors at its base, which rotate in counterclockwise clockwise directions to achieve "run" "tumble." The regulated network interacting proteins. sensory signal processed transmitted motor cytoplasmic plays an important role many biological processes such biofilm formation, quorum sensing, bacterial pathogenesis, host infection. can be applied for bioremediation, horizontal gene transfer, drug delivery, maybe some other industry near future. review contains overview chemotaxis, recent findings physiological importance processes, application chemotaxis.

Language: Английский

Citations

82
New Understanding of the Relevant Role of LINE-1 Retrotransposition in Human Disease and Immune Modulation DOI Creative Commons
Xiao Zhang, Rui Zhang, Jinpu Yu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Aug. 7, 2020

Long interspersed nuclear element-1 (LINE-1) retrotransposition is a major hallmark of cancer accompanied by global chromosomal instability, genomic and genetic heterogeneity has become one indicator for the occurrence, development, poor prognosis many diseases. LINE-1 also modulates immune system affects microenvironment in variety ways. Aberrant expression retrotransposon can provide strong stimuli an innate response, activate system, induce autoimmunity inflammation. Therefore, inhibition activity potential treatment strategy various In this review, we discussed components regulatory mechanisms involved with LINE-1, its correlations disease immunity, multiple inhibitors providing new understanding LINE-1.

Language: Английский

Citations

78
Silencing of LINE-1 retrotransposons is a selective dependency of myeloid leukemia DOI
Zhimin Gu, Yuxuan Liu,

Yuannyu Zhang

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(5), P. 672 - 682

Published: April 8, 2021

Language: Английский

Citations

76
Structural variants are a major source of gene expression differences in humans and often affect multiple nearby genes DOI Creative Commons
Alexandra J. Scott, Colby Chiang, Ira M. Hall

et al.

Genome Research, Journal Year: 2021, Volume and Issue: 31(12), P. 2249 - 2257

Published: Sept. 20, 2021

Structural variants (SVs) are an important source of human genome diversity, but their functional effects poorly understood. We mapped 61,668 SVs in 613 individuals from the GTEx project and measured on gene expression. estimate that common causal at 2.66% eQTLs, a 10.5-fold enrichment relative to abundance genome. Duplications deletions were most impactful variant types, whereas contribution mobile element insertions was small (0.12% 1.9-fold enriched). Multitissue analysis eQTLs revealed gene-altering show more constitutive than other with 62.09% coding SV-eQTLs active all tissues eQTL activity compared 23.08% SNV- indel-eQTLs. Noncoding SVs, SNVs indels broadly similar patterns. also identified 539 rare associated nearby expression outliers. Of these, 62.34% noncoding affect have modest regulatory elements, showing major differences remain difficult predict current annotations. Both often multiple genes: average 1.82 genes, indel-eQTLs 1.09 21.34% expression-altering two nine different genes. observe significant changes extending 1 Mb SV. This provides mechanism by which individual may strong or pleiotropic phenotypic variation.

Language: Английский

Citations

73
RNA m6A modification orchestrates a LINE-1–host interaction that facilitates retrotransposition and contributes to long gene vulnerability DOI Creative Commons
Feng Xiong, Ruoyu Wang, Joo‐Hyung Lee

et al.

Cell Research, Journal Year: 2021, Volume and Issue: 31(8), P. 861 - 885

Published: June 9, 2021

Abstract The molecular basis underlying the interaction between retrotransposable elements (RTEs) and human genome remains poorly understood. Here, we profiled N 6 -methyladenosine (m A) deposition on nascent RNAs in cells by developing a new method MINT-Seq, which revealed that many classes of RTE RNAs, particularly intronic LINE-1s (L1s), are strongly methylated. These m A-marked i ntronic L 1s (MILs) evolutionarily young, sense-oriented to hosting genes, bound dozen RNA binding proteins (RBPs) putative novel readers A-modified including nuclear matrix protein SAFB. Notably, A positively controls expression both autonomous L1s co-transcribed L1 relics, promoting retrotransposition. We showed MILs preferentially reside long genes with critical roles DNA damage repair sometimes suppression per se, where they act as transcriptional “roadblocks” impede gene expression, revealing host-weakening strategy L1s. In counteraction, host uses SAFB reader complex bind A-L1s reduce their levels, safeguard transcription. Remarkably, our analysis identified thousands multiple fetal tissues, enlisting them category cell-type-specific regulatory often compromise transcription confer vulnerability neurodevelopmental disorders. propose this A-orchestrated L1–host plays widespread regulation, integrity, development diseases.

Language: Английский

Citations

64