ORCID Profile
0000-0001-5769-4494
Current Organisations
The University of Queensland Queensland Brain Institute
,
Mater Research Institute The University of Queensland
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Genome Structure and Regulation | Genetics | Developmental Genetics (incl. Sex Determination) | Genomics | Molecular Evolution | Neurogenetics
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2011
Abstract: Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE. nanoCAGE analysis revealed the map and architecture of promoters for 87.5% of the mouse OR genes, as well as the expression of many novel noncoding RNAs including antisense transcripts. We identified candidate transcription factors for OR gene expression and among them confirmed by chromatin immunoprecipitation the binding of TBP, EBF1 (OLF1), and MEF2A to OR promoters. Finally, we showed that a short genomic fragment flanking the major TSS of the OR gene Olfr160 ( M72 ) can drive OSN-specific expression in transgenic mice.
Publisher: Cold Spring Harbor Laboratory
Date: 20-03-2022
DOI: 10.1101/2022.03.20.485017
Abstract: Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes 1–3 . Developmental programs that activate TE-derived regulatory elements could, in principle, manifest in lineage-specific TE mobility. While somatic LINE-1 (L1) retrotransposon insertions have been detected in human neurons 4–6 , the impact of L1 insertions on neurodevelopmental gene regulation, and whether L1 mobility is restricted to certain neuronal lineages, is unknown. Here, we reveal programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV + ) interneuron development 7–9 . PV + neurons harbor unmethylated and euchromatic L1 promoters, express L1 mRNA, and permit L1 transgene mobilization in vivo . Elevated L1 expression in adult dentate gyrus PV + neurons is however attenuated by environmental enrichment. Nanopore sequencing of PV + neurons identifies unmethylated L1 loci providing alternative promoters to core PV + neuron genes, such as CAPS2. These data depict SOX6-mediated L1 activation as an ingrained component of the mammalian PV + neuron developmental program.
Publisher: Springer Science and Business Media LLC
Date: 07-2009
DOI: 10.1038/NG0709-859A
Publisher: Oxford University Press (OUP)
Date: 08-04-2004
DOI: 10.1093/BIOINFORMATICS/BTH226
Abstract: Summary: Bellerophon is a program for detecting chimeric sequences in multiple sequence datasets by an adaption of partial treeing analysis. Bellerophon was specifically developed to detect 16S rRNA gene chimeras in PCR-clone libraries of environmental s les but can be applied to other nucleotide sequence alignments. Availability: Bellerophon is available as an interactive web server at foo.maths.uq.edu.au/~huber/bellerophon.pl
Publisher: Springer Science and Business Media LLC
Date: 19-04-2009
DOI: 10.1038/NG.312
Abstract: It has been reported that relatively short RNAs of heterogeneous sizes are derived from sequences near the promoters of eukaryotic genes. In conjunction with the FANTOM4 project, we have identified tiny RNAs with a modal length of 18 nt that map within -60 to +120 nt of transcription start sites (TSSs) in human, chicken and Drosophila. These transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the TSS and are preferentially associated with G+C-rich promoters. The 5' ends of tiRNAs show peak density 10-30 nt downstream of TSSs, indicating that they are processed. tiRNAs are generally, although not exclusively, associated with highly expressed transcripts and sites of RNA polymerase II binding. We suggest that tiRNAs may be a general feature of transcription in metazoa and possibly all eukaryotes.
Publisher: Springer Science and Business Media LLC
Date: 22-06-2018
Publisher: Springer Science and Business Media LLC
Date: 07-07-2018
Publisher: Springer Science and Business Media LLC
Date: 27-01-2023
DOI: 10.1038/S41416-023-02154-9
Abstract: Molecular characterisation of hepatocellular carcinoma (HCC) is central to the development of novel therapeutic strategies for the disease. We have previously demonstrated mutagenic consequences of Long-Interspersed Nuclear Element-1 (LINE1s/L1) retrotransposition. However, the role of L1 in HCC, besides somatic mutagenesis, is not well understood. We analysed L1 expression in the TCGA-HCC RNAseq dataset ( n = 372) and explored potential relationships between L1 expression and clinical features. The findings were confirmed by immunohistochemical (IHC) analysis of an independent human HCC cohort ( n = 48) and functional mechanisms explored using in vitro and in vivo model systems. We observed positive associations between L1 and activated TGFβ-signalling, TP53 mutation, alpha-fetoprotein and tumour invasion. IHC confirmed a positive association between pSMAD3, a surrogate for TGFβ-signalling status, and L1 ORF1p ( P 0.0001, n = 32). Experimental modulation of L1 ORF1p levels revealed an influence of L1 ORF1p on key hepatocarcinogenesis-related pathways. Reduction in cell migration and invasive capacity was observed upon L1 ORF1 knockdown, both in vitro and in vivo. In particular, L1 ORF1p increased PIN1 cytoplasmic localisation. Blocking PIN1 activity abrogated L1 ORF1p-induced NF-κB-mediated inflammatory response genes while further activated TGFβ-signalling confirming differential alteration of PIN1 activity in cellular compartments by L1 ORF1p. Our data demonstrate a causal link between L1 ORF1p and key oncogenic pathways mediated by PIN1, presenting a novel therapeutic avenue.
Publisher: Springer Science and Business Media LLC
Date: 03-12-2022
DOI: 10.1038/S41467-022-35180-X
Abstract: Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing to 38 bulk miPSC lines reprogrammed from 10 parental cell types, and 18 single-cell miPSC clones. While single nucleotide variants and structural variants restricted to miPSCs are rare, we find 83 de novo transposable element insertions, including ex les intronic to Brca1 and Dmd . LINE-1 retrotransposons are profoundly hypomethylated in miPSCs, beyond other transposable elements and the genome overall, and harbor alternative protein-coding gene promoters. We show that treatment with the LINE-1 inhibitor lamivudine does not hinder reprogramming and efficiently blocks endogenous retrotransposition, as detected by long-read genome sequencing. These experiments reveal the complete spectrum and potential significance of mutations acquired by miPSCs.
Publisher: Cold Spring Harbor Laboratory
Date: 11-09-2012
Abstract: L1 retrotransposons comprise 17% of the human genome and are its only autonomous mobile elements. Although L1-induced insertional mutagenesis causes Mendelian disease, their mutagenic load in cancer has been elusive. Using L1-targeted resequencing of 16 colorectal tumor and matched normal DNAs, we found that certain cancers were excessively mutagenized by human-specific L1s, while no verifiable insertions were present in normal tissues. We confirmed de novo L1 insertions in malignancy by both validating and sequencing 69/107 tumor-specific insertions and retrieving both 5′ and 3′ junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 5′ truncated. Validated insertion numbers varied from up to 17 in some tumors to none in three others, and correlated with the age of the patients. Numerous genes with a role in tumorigenesis were targeted, including ODZ3 , ROBO2 , PTPRM , PCM1 , and CDH11 . Thus, somatic retrotransposition may play an etiologic role in colorectal cancer.
Publisher: Wiley
Date: 25-02-2014
Publisher: Public Library of Science (PLoS)
Date: 06-03-2017
Publisher: Springer Science and Business Media LLC
Date: 16-08-2023
DOI: 10.1038/S41586-023-06424-7
Abstract: Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function 1–8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
Publisher: Springer Science and Business Media LLC
Date: 31-03-2022
Publisher: Cold Spring Harbor Laboratory
Date: 05-01-2010
Abstract: MicroRNAs (miRNAs) are short (20–23 nt) RNAs that are sequence-specific mediators of transcriptional and post-transcriptional regulation of gene expression. Modern high-throughput technologies enable deep sequencing of such RNA species on an unprecedented scale. We find that the analysis of small RNA deep-sequencing libraries can be affected by cross-mapping, in which RNA sequences originating from one locus are inadvertently mapped to another. Similar to cross-hybridization on microarrays, cross-mapping is prevalent among miRNAs, as they tend to occur in families, are similar or derived from repeat or structural RNAs, or are post-transcriptionally modified. Here, we develop a strategy to correct for cross-mapping, and apply it to the analysis of RNA editing in mature miRNAs. In contrast to previous reports, our analysis suggests that RNA editing in mature miRNAs is rare in animals.
Publisher: Informa UK Limited
Date: 04-2019
DOI: 10.1128/MCB.00499-18
Publisher: Cold Spring Harbor Laboratory
Date: 07-10-2022
DOI: 10.1101/2022.10.06.511227
Abstract: A recent study (Takahashi et al., Neuron , 2022) concluded LINE-1 (L1) retrotransposon activation drives cerebellar ataxia and neurodegeneration. This position was based on L1 upregulation in ataxia telangiectasia (AT) patient cerebellum s les, as measured by RNA-seq, and observation of ataxia and neurodegeneration in mice where cerebellar L1 expression was induced via dCas9-CRISPR. Here, a re-analysis of the RNA-seq data, which were obtained by rRNA depletion rather than polyA+ selection, revealed a high fraction (38.4%) of intronic reads. Significantly ( p =0.034) more intronic reads were present in the AT data than the matched controls. This finding provides an alternative and robust explanation for a key result reported by Takahashi et al.: intronic L1 sequences are abundant in pre-mRNAs, and more pre-mRNAs were retained in the AT libraries. This apparent batch effect deserves further examination, as claims of L1-mediated pathogenesis could shape future efforts to treat AT by trying to attenuate L1 activity.
Publisher: Cold Spring Harbor Laboratory
Date: 17-04-2022
DOI: 10.1101/2022.04.17.488603
Abstract: This study establishes the homeodomain only protein, HOPX, as a determinant controlling the molecular switch between cardiomyocyte progenitor and maturation gene programs. Time-course single-cell gene expression with genome-wide footprinting reveal that HOPX interacts with and controls core cardiac networks by regulating the activity of mutually exclusive developmental gene programs. Upstream hypertrophy and proliferation pathways compete to regulate HOPX transcription. Mitogenic signals override hypertrophic growth signals to suppress HOPX and maintain cardiomyocyte progenitor gene programs. Physiological studies show HOPX directly governs genetic control of cardiomyocyte cell stress responses, electro-mechanical coupling, proliferation, and contractility. We use human genome-wide association studies (GWAS) to show that genetic variation in the HOPX-regulome is significantly associated with complex traits affecting cardiac structure and function. Collectively, this study provides a mechanistic link situating HOPX between competing upstream pathways where HOPX acts as a molecular switch controlling gene regulatory programs underpinning metabolic, signaling, and functional maturation of cardiomyocytes.
Publisher: Cold Spring Harbor Laboratory
Date: 11-04-2018
Abstract: The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) s les from patients infected with hepatitis B or hepatitis C virus and identified L1 variants responsible for activating oncogenic pathways. Here, we have applied RC-seq and whole-genome sequencing (WGS) to an Abcb4 (Mdr2) −/− mouse model of hepatic carcinogenesis and demonstrated for the first time that L1 mobilization occurs in murine tumors. In 12 HCC nodules obtained from 10 animals, we validated four somatic L1 insertions by PCR and capillary sequencing, including T F subfamily elements, and one G F subfamily ex le. One of the T F insertions carried a 3′ transduction, allowing us to identify its donor L1 and to demonstrate that this full-length T F element retained retrotransposition capacity in cultured cancer cells. Using RC-seq, we also identified eight tumor-specific L1 insertions from 25 HCC patients with a history of alcohol abuse. Finally, we used RC-seq and WGS to identify three tumor-specific L1 insertions among 10 intra-hepatic cholangiocarcinoma (ICC) patients, including one insertion traced to a donor L1 on Chromosome 22 known to be highly active in other cancers. This study reveals L1 mobilization as a common feature of hepatocarcinogenesis in mammals, demonstrating that the phenomenon is not restricted to human viral HCC etiologies and is encountered in murine liver tumors.
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2022
Abstract: The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic ersity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the ergence of apes and Old World monkeys, successive L1 subfamilies have emerged in each descendant primate germline. As revealed by case studies, the presently active human L1 subfamily can also mobilize during embryonic and brain development in vivo. It is unknown whether nonhuman primate L1s can similarly generate somatic insertions in the brain. Here we applied approximately 40× single-cell whole-genome sequencing (scWGS), as well as retrotransposon capture sequencing (RC-seq), to 20 hippoc al neurons from two rhesus macaques ( Macaca mulatta ). In one animal, we detected and PCR-validated a somatic L1 insertion that generated target site duplications, carried a short 5′ transduction, and was present in ∼7% of hippoc al neurons but absent from cerebellum and nonbrain tissues. The corresponding donor L1 allele was exceptionally mobile in vitro and was embedded in PRDM4 , a gene expressed throughout development and in neural stem cells. Nanopore long-read methylome and RNA-seq transcriptome analyses indicated young retrotransposon subfamily activation in the early embryo, followed by repression in adult tissues. These data highlight endogenous macaque L1 retrotransposition potential, provide prototypical evidence of L1-mediated somatic mosaicism in a nonhuman primate, and allude to L1 mobility in the brain over the past 30 million years of human evolution.
Publisher: Elsevier BV
Date: 04-2011
Publisher: Springer Science and Business Media LLC
Date: 30-05-2008
DOI: 10.1038/NMETH.1223
Abstract: We developed a massive-scale RNA sequencing protocol, short quantitative random RNA libraries or SQRL, to survey the complexity, dynamics and sequence content of transcriptomes in a near-complete fashion. This method generates directional, random-primed, linear cDNA libraries that are optimized for next-generation short-tag sequencing. We surveyed the poly(A)(+) transcriptomes of undifferentiated mouse embryonic stem cells (ESCs) and embryoid bodies (EBs) at an unprecedented depth (10 Gb), using the Applied Biosystems SOLiD technology. These libraries capture the genomic landscape of expression, state-specific expression, single-nucleotide polymorphisms (SNPs), the transcriptional activity of repeat elements, and both known and new alternative splicing events. We investigated the impact of transcriptional complexity on current models of key signaling pathways controlling ESC pluripotency and differentiation, highlighting how SQRL can be used to characterize transcriptome content and dynamics in a quantitative and reproducible manner, and suggesting that our understanding of transcriptional complexity is far from complete.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Springer Science and Business Media LLC
Date: 11-11-2016
Publisher: Wiley
Date: 27-09-2021
Abstract: Processed pseudogenes may serve as a genetic reservoir for evolutionary innovation. Here, we argue that through the activity of long interspersed element‐1 retrotransposons, processed pseudogenes disperse coding and noncoding sequences rich with regulatory potential throughout the human genome. While these sequences may appear to be non‐functional, a lack of contemporary function does not prohibit future development of biological activity. Here, we discuss the dynamic evolution of certain processed pseudogenes into coding and noncoding genes and regulatory elements, and their implication in wide‐ranging biological and pathological processes. Also see the video abstract here: youtu.be/iUY_mteVoPI
Publisher: The Royal Society
Date: 07-2018
DOI: 10.1098/RSOB.180074
Abstract: Over the past decade, major discoveries in retrotransposon biology have depicted the neural genome as a dynamic structure during life. In particular, the retrotransposon LINE-1 (L1) has been shown to be transcribed and mobilized in the brain. Retrotransposition in the developing brain, as well as during adult neurogenesis, provides a milieu in which neural ersity can arise. Dysregulation of retrotransposon activity may also contribute to neurological disease. Here, we review recent reports of retrotransposon activity in the brain, and discuss the temporal nature of retrotransposition and its regulation in neural cells in response to stimuli. We also put forward hypotheses regarding the significance of retrotransposons for brain development and neurological function, and consider the potential implications of this phenomenon for neuropsychiatric and neurodegenerative conditions.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2021
DOI: 10.1186/S13059-021-02369-0
Abstract: Pseudogenes are gene copies presumed to mainly be functionless relics of evolution due to acquired deleterious mutations or transcriptional silencing. Using deep full-length PacBio cDNA sequencing of normal human tissues and cancer cell lines, we identify here hundreds of novel transcribed pseudogenes expressed in tissue-specific patterns. Some pseudogene transcripts have intact open reading frames and are translated in cultured cells, representing unannotated protein-coding genes. To assess the biological impact of noncoding pseudogenes, we CRISPR-Cas9 delete the nucleus-enriched pseudogene PDCL3P4 and observe hundreds of perturbed genes. This study highlights pseudogenes as a complex and dynamic component of the human transcriptional landscape.
Publisher: MDPI AG
Date: 11-10-2021
Abstract: Hepatitis C virus (HCV) is a common cause of hepatocellular carcinoma (HCC). The activation and mutagenic consequences of L1 retrotransposons in virus-associated-HCC have been documented. However, the direct influence of HCV upon L1 elements is unclear, and is the focus of the present study. L1 transcript expression was evaluated in a publicly available liver tissue RNA-seq dataset from patients with chronic HCV hepatitis (CHC), as well as healthy controls. L1 transcript expression was significantly higher in CHC than in controls. L1orf1p (a L1 encoded protein) expression was observed in six out of 11 CHC livers by immunohistochemistry. To evaluate the influence of HCV on retrotransposition efficiency, in vitro engineered-L1 retrotransposition assays were employed in Huh7 cells in the presence and absence of an HCV replicon. An increased retrotransposition rate was observed in the presence of replicating HCV RNA, and persisted in cells after viral clearance due to sofosbuvir (PSI7977) treatment. Increased retrotransposition could be due to dysregulation of the DNA-damage repair response, including homologous recombination, due to HCV infection. Altogether these data suggest that L1 expression can be activated before oncogenic transformation in CHC patients, with HCV-upregulated retrotransposition potentially contributing to HCC genomic instability and a risk of transformation that persists post-viral clearance.
Publisher: Society for Neuroscience
Date: 06-11-2013
DOI: 10.1523/JNEUROSCI.3369-13.2013
Abstract: First discovered in maize by Barbara McClintock in the 1940s, transposable elements (TEs) are DNA sequences that in some cases have the ability to move along chromosomes or “transpose” in the genome. This revolutionary finding was initially met with resistance by the scientific community and viewed by some as heretical. A large body of knowledge has accumulated over the last 60 years on the biology of TEs. Indeed, it is now known that TEs can generate genomic instability and reconfigure gene expression networks both in the germline and somatic cells. This review highlights recent findings on the role of TEs in health and diseases of the CNS, which were presented at the 2013 Society for Neuroscience meeting. The work of the speakers in this symposium shows that TEs are expressed and active in the brain, challenging the dogma that neuronal genomes are static and revealing that they are susceptible to somatic genomic alterations. These new findings on TE expression and function in the CNS have major implications for understanding the neuroplasticity of the brain, which could hypothetically have a role in shaping in idual behavior and contribute to vulnerability to disease.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2016
Publisher: Springer Science and Business Media LLC
Date: 03-2014
DOI: 10.1038/NATURE13182
Publisher: Frontiers Media SA
Date: 2014
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-02-2015
Abstract: In order to understand cellular differentiation, it is important to understand the timing of the regulation of gene expression. Arner et al. used cap analysis of gene expression (CAGE) to analyze gene enhancer and promoter activities in a number of human and mouse cell types. The RNA of enhancers was transcribed first, followed by that of transcription factors, and finally by genes that are not transcription factors. Science , this issue p. 1010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-12-2016
DOI: 10.1002/HEP.28942
Abstract: The ST18 gene has been proposed to act either as a tumor suppressor or as an oncogene in different human cancers, but direct evidence for its role in tumorigenesis has been lacking thus far. Here, we demonstrate that ST18 is critical for tumor progression and maintenance in a mouse model of liver cancer, based on oncogenic transformation and adoptive transfer of primary precursor cells (hepatoblasts). ST18 messenger RNA (mRNA) and protein were detectable neither in normal liver nor in cultured hepatoblasts, but were readily expressed after subcutaneous engraftment and tumor growth. ST18 expression in liver cells was induced by inflammatory cues, including acute or chronic inflammation in vivo , as well as coculture with macrophages in vitro . Knocking down the ST18 mRNA in transplanted hepatoblasts delayed tumor progression. Induction of ST18 knockdown in pre‐established tumors caused rapid tumor involution associated with pervasive morphological changes, proliferative arrest, and apoptosis in tumor cells, as well as depletion of tumor‐associated macrophages, vascular ectasia, and hemorrhage. Reciprocally, systemic depletion of macrophages in recipient animals had very similar phenotypic consequences, impairing either tumor development or maintenance, and suppressing ST18 expression in hepatoblasts. Finally, RNA sequencing of ST18 ‐depleted tumors before involution revealed down‐regulation of inflammatory response genes, pointing to the suppression of nuclear factor kappa B–dependent transcription. Conclusion : ST18 expression in epithelial cells is induced by tumor‐associated macrophages, contributing to the reciprocal feed‐forward loop between both cell types in liver tumorigenesis. Our findings warrant the exploration of means to interfere with ST18‐dependent epithelium–macrophage interactions in a therapeutic setting. (H epatology 2017 :1708‐1719).
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.MOLCEL.2022.04.013
Abstract: Garland et al. (2022) discover a physical and functional connection between the HUSH silencing complex and the NEXT nuclear RNA decay complex in mouse embryonic stem cells and conclude HUSH recruits NEXT to degrade prematurely terminated retrotransposon RNAs.
Publisher: University of Queensland Library
Date: 2008
DOI: 10.14264/167578
Publisher: Oxford University Press (OUP)
Date: 30-07-2009
DOI: 10.1093/BIOINFORMATICS/BTP459
Abstract: Summary: Mapping of next-generation sequencing data derived from RNA s les (RNAseq) presents different genome mapping challenges than data derived from DNA. For ex le, tags that cross exon-junction boundaries will often not map to a reference genome, and the strand specificity of the data needs to be retained. Here we present RNA-MATE, a computational pipeline based on a recursive mapping strategy for placing strand specific RNAseq data onto a reference genome. Maximizing the mappable tags can provide significant savings in the cost of sequencing experiments. This pipeline provides an automatic and integrated way to align color-space sequencing data, collate this information and generate files for examining gene-expression data in a genomic context. Availability: Executables, source code, and exon-junction libraries are available from grimmond.imb.uq.edu.au/RNA-MATE/ Contact: n.cloonan@imb.uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics Online.
Publisher: Wiley
Date: 28-11-2014
DOI: 10.1111/FEBS.12601
Publisher: Springer US
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 29-08-2017
Abstract: In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of s les, consisting of a variety of primary cells, tissues, cell lines, and time series s les during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
Publisher: Public Library of Science (PLoS)
Date: 18-12-2015
Publisher: Cold Spring Harbor Laboratory
Date: 18-01-2019
DOI: 10.1101/522623
Abstract: Long Interspersed Element 1 (LINE-1/L1) is an abundant retrotransposon that has greatly impacted human genome evolution. LINE-1s are responsible for the generation of millions of insertions in the current human population. The characterization of sporadic cases of mosaic in iduals carrying pathogenic L1-insertions, suggest that heritable insertions occurs during early embryogenesis. However, the timing and potential genomic impact of LINE-1 mobilization during early embryogenesis is unknown. Here, we demonstrate that inner cell mass of human pre-implantation embryos support the expression and retrotransposition of LINE −1s. Additionally, we show that LINE-1s are expressed in trophectoderm cells of embryos, and identify placenta-restricted endogenous LINE-1 insertions in newborns. Using human embryonic stem cells as a model of post-implantation epiblast cells, we demonstrate ongoing LINE-1 retrotransposition, which can impact expression of targeted genes. Our data demonstrate that LINE-1 retrotransposition starts very shortly after fertilization and may represent a previously underappreciated factor in human biology and disease.
Publisher: Oxford University Press (OUP)
Date: 15-07-2019
DOI: 10.1093/NAR/GKZ599
Abstract: RNA-Seq is a powerful transcriptome profiling technology enabling transcript discovery and quantification. Whilst most commonly used for gene-level quantification, the data can be used for the analysis of transcript isoforms. However, when the underlying transcript assemblies are complex, current visualization approaches can be limiting, with splicing events a challenge to interpret. Here, we report on the development of a graph-based visualization method as a complementary approach to understanding transcript ersity from short-read RNA-Seq data. Following the mapping of reads to a reference genome, a read-to-read comparison is performed on all reads mapping to a given gene, producing a weighted similarity matrix between reads. This is used to produce an RNA assembly graph, where nodes represent reads and edges similarity scores between them. The resulting graphs are visualized in 3D space to better appreciate their sometimes large and complex topology, with other information being overlaid on to nodes, e.g. transcript models. Here we demonstrate the utility of this approach, including the unusual structure of these graphs and how they can be used to identify issues in assembly, repetitive sequences within transcripts and splice variants. We believe this approach has the potential to significantly improve our understanding of transcript complexity.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Annual Reviews
Date: 23-11-2014
DOI: 10.1146/ANNUREV-GENET-120213-092412
Abstract: Long interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intrain idual genetic ersity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo. We compare experimental strategies used to map de novo somatic retrotransposition events and present the optimal criteria to identify a somatic L1 insertion. Finally, we discuss the unresolved impact of L1-mediated somatic mosaicism upon normal neurobiology, as well as its potential to drive neurological disease.
Publisher: Springer Science and Business Media LLC
Date: 17-12-2020
DOI: 10.1038/S41576-019-0196-1
Abstract: Pseudogenes are defined as regions of the genome that contain defective copies of genes. They exist across almost all forms of life, and in mammalian genomes are annotated in similar numbers to recognized protein-coding genes. Although often presumed to lack function, growing numbers of pseudogenes are being found to play important biological roles. In consideration of their evolutionary origins and inherent limitations in genome annotation practices, we posit that pseudogenes have been classified on a scientifically unsubstantiated basis. We reflect that a broad misunderstanding of pseudogenes, perpetuated in part by the pejorative inference of the 'pseudogene' label, has led to their frequent dismissal from functional assessment and exclusion from genomic analyses. With the advent of technologies that simplify the study of pseudogenes, we propose that an objective reassessment of these genomic elements will reveal valuable insights into genome function and evolution.
Publisher: Springer Science and Business Media LLC
Date: 02-06-2021
DOI: 10.1038/S41467-021-23143-7
Abstract: Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
Publisher: Springer Science and Business Media LLC
Date: 2003
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.TIG.2009.11.002
Abstract: The current view of gene regulation in complex organisms holds that gene expression is largely controlled by the combinatoric actions of transcription factors and other regulatory proteins, some of which powerfully influence cell type. Recent large-scale studies have confirmed that cellular differentiation involves many different regulatory factors. However, other studies indicate that the genome is pervasively transcribed to produce a variety of short and long non-protein-coding RNAs, including those derived from retrotransposed sequences, which also play important roles in the epigenetic regulation of gene expression. The evidence suggests that ontogenesis requires interplay between state-specific regulatory proteins, multitasked effector complexes and target-specific RNAs that recruit these complexes to their sites of action. Moreover, the semi-continuous nature of the transcriptome prompts the reassessment of 'genes' as discrete entities and indicates that the mammalian genome might be more accurately viewed as islands of protein-coding information in a sea of cis- and trans-acting regulatory sequences.
Publisher: Wiley
Date: 30-04-2018
Publisher: Springer Science and Business Media LLC
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 2006
Publisher: Public Library of Science (PLoS)
Date: 07-11-2013
Publisher: Springer Science and Business Media LLC
Date: 12-2016
Publisher: Wiley
Date: 31-08-2022
DOI: 10.1111/BPA.13018
Abstract: Age is one of the strongest risk factors for the development of neurodegenerative diseases, the majority of which involve misfolded protein aggregates in the brain. These protein aggregates are thought to drive pathology and are attractive targets for the development of new therapies. However, it is unclear how age influences the onset of pathology and the accompanying molecular response. To address this knowledge gap, we used a model of seeded tau pathology to profile the transcriptomic changes in 3 and 12 month old mice in response to developing tau hyperphosphorylation and aggregation. First, we found the burden of hyperphosphorylated tau pathology in mice injected at 12 months of age was moderately reduced compared to animals injected at 3 months. On a molecular level, we found an inflammation‐related subset of genes, including C3 and the disease‐associated microglia genes Ctsd , Cst7 , and Clec7a , were more expressed early in disease in 12 but not 3 month old mice. These findings provide evidence of an early, age‐specific response to tau pathology, which could serve as a marker for the severity of downstream pathology.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.TIG.2017.07.004
Abstract: The retrotransposon LINE-1 (long interspersed element 1, L1) is a transposable element that has extensively colonized the mammalian germline. L1 retrotransposition can also occur in somatic cells, causing genomic mosaicism, as well as in cancer. However, the extent of L1-driven mosaicism arising during ontogenesis is unclear. We discuss here recent experimental data which, at a minimum, fully substantiate L1 mosaicism in early embryonic development and neural cells, including post-mitotic neurons. We also consider the possible biological impact of somatic L1 insertions in neurons, the existence of donor L1s that are highly active ('hot') in specific spatiotemporal niches, and the evolutionary selection of donor L1s driving neuronal mosaicism.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.CELREP.2018.05.090
Abstract: LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood s les from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2021
DOI: 10.1186/S13059-021-02357-4
Abstract: Endogenous retroviruses (ERVs) are emerging as promising therapeutic targets in cancer. As remnants of ancient retroviral infections, ERV-derived regulatory elements coordinate expression from gene networks, including those underpinning embryogenesis and immune cell function. ERV activation can promote an interferon response, a phenomenon termed viral mimicry. Although ERV expression is associated with cancer, and provisionally with autoimmune and neurodegenerative diseases, ERV-mediated inflammation is being explored as a way to sensitize tumors to immunotherapy. Here we review ERV co-option in development and innate immunity, the aberrant contribution of ERVs to tumorigenesis, and the wider biomedical potential of therapies directed at ERVs.
Publisher: Proceedings of the National Academy of Sciences
Date: 26-03-2012
Abstract: Evolutionary change in gene expression is generally considered to be a major driver of phenotypic differences between species. We investigated innate immune ersification by analyzing interspecies differences in the transcriptional responses of primary human and mouse macrophages to the Toll-like receptor (TLR)–4 agonist lipopolysaccharide (LPS). By using a custom platform permitting cross-species interrogation coupled with deep sequencing of mRNA 5′ ends, we identified extensive ergence in LPS-regulated orthologous gene expression between humans and mice (24% of orthologues were identified as “ ergently regulated”). We further demonstrate concordant regulation of human-specific LPS target genes in primary pig macrophages. Divergently regulated orthologues were enriched for genes encoding cellular “inputs” such as cell surface receptors (e.g., TLR6, IL-7Rα) and functional “outputs” such as inflammatory cytokines/chemokines (e.g., CCL20, CXCL13). Conversely, intracellular signaling components linking inputs to outputs were typically concordantly regulated. Functional consequences of ergent gene regulation were confirmed by showing LPS pretreatment boosts subsequent TLR6 responses in mouse but not human macrophages, in keeping with mouse-specific TLR6 induction. Divergently regulated genes were associated with a large dynamic range of gene expression, and specific promoter architectural features (TATA box enrichment, CpG island depletion). Surprisingly, regulatory ergence was also associated with enhanced interspecies promoter conservation. Thus, the genes controlled by complex, highly conserved promoters that facilitate dynamic regulation are also the most susceptible to evolutionary change.
Publisher: Elsevier BV
Date: 05-2016
Publisher: Springer Science and Business Media LLC
Date: 17-11-2022
Publisher: Wiley
Date: 27-06-2022
DOI: 10.1111/JPC.16088
Publisher: Informa UK Limited
Date: 15-09-2009
DOI: 10.4161/CC.8.18.9536
Abstract: Mammalian genomes are comprised of 30-50% transposed elements (TEs). The vast majority of these TEs are truncated and mutated fragments of retrotransposons that are no longer capable of transposition. Although initially regarded as important factors in the evolution of gene regulatory networks, TEs are now commonly perceived as neutrally evolving and non-functional genomic elements. In a major development, recent works have strongly contradicted this "selfish DNA" or "junk DNA" dogma by demonstrating that TEs use a host of novel promoters to generate RNA on a massive scale across most eukaryotic cells. This transcription frequently functions to control the expression of protein-coding genes via alternative promoters, cis regulatory non protein-coding RNAs and the formation of double stranded short RNAs. If considered in sum, these findings challenge the designation of TEs as selfish and neutrally evolving genomic elements. Here, we will expand upon these themes and discuss challenges in establishing novel TE functions in vivo.
Publisher: Elsevier BV
Date: 02-2011
Publisher: Springer Science and Business Media LLC
Date: 16-10-2013
DOI: 10.1038/SREP02962
Abstract: Metastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for ex le, TERC , which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2 and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue s les for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity.
Publisher: Springer New York
Date: 2017
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 30-10-2011
DOI: 10.1038/NATURE10531
Publisher: Springer Science and Business Media LLC
Date: 11-2012
DOI: 10.1038/NATURE11622
Publisher: Springer New York
Date: 2016
DOI: 10.1007/978-1-4939-3372-3_4
Abstract: Mobile genetic elements (MGEs) are of critical importance in genomics and developmental biology. Polymorphic and somatic MGE insertions have the potential to impact the phenotype of an in idual, depending on their genomic locations and functional consequences. However, the identification of polymorphic and somatic insertions among the plethora of copies residing in the genome presents a formidable technical challenge. Whole genome sequencing has the potential to address this problem however, its efficacy depends on the abundance of cells carrying the new insertion. Robust detection of somatic insertions present in only a subset of cells within a given s le can also be prohibitively expensive due to a requirement for high sequencing depth. Here, we describe retrotransposon capture sequencing (RC-seq), a sequence capture approach in which Illumina libraries are enriched for fragments containing the 5' and 3' termini of specific MGEs. RC-seq allows the detection of known polymorphic insertions present in an in idual, as well as the identification of rare or private germline insertions not previously described. Furthermore, RC-seq can be used to detect and characterize somatic insertions, providing a valuable tool to elucidate the extent and characteristics of MGE activity in healthy tissues and in various disease states.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2017
DOI: 10.1038/NATURE23277
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.YGENO.2007.11.003
Abstract: Cap analysis gene expression (CAGE) is a high-throughput, tag-based method designed to survey the 5' end of capped full-length cDNAs. CAGE has previously been used to define global transcription start site usage and monitor gene activity in mammals. A drawback of the CAGE approach thus far has been the removal of as many as 40% of CAGE sequence tags due to their mapping to multiple genomic locations. Here, we address the origins of multimap tags and present a novel strategy to assign CAGE tags to their most likely source promoter region. When this approach was applied to the FANTOM3 CAGE libraries, the percentage of protein-coding mouse transcriptional frameworks detected by CAGE improved from 42.9 to 57.8% (an increase of 5516 frameworks) with no reduction in CAGE to microarray correlation. These results suggest that the multimap tags produced by high-throughput, short sequence tag-based approaches can be rescued to augment greatly the transcriptome coverage provided by single-map tags alone.
Publisher: Cold Spring Harbor Laboratory
Date: 06-2003
DOI: 10.1101/GR.1056103
Abstract: The current RIKEN transcript set represents a significant proportion of the mouse transcriptome but transcripts expressed in the innate and acquired immune systems are poorly represented. In the present study we have assessed the complexity of the transcriptome expressed in mouse macrophages before and after treatment with lipopolysaccharide, a global regulator of macrophage gene expression, using existing RIKEN 19K arrays. By comparison to array profiles of other cells and tissues, we identify a large set of macrophage-enriched genes, many of which have obvious functions in endocytosis and phagocytosis. In addition, a significant number of LPS-inducible genes were identified. The data suggest that macrophages are a complex source of mRNA for transcriptome studies. To assess complexity and identify additional macrophage expressed genes, cDNA libraries were created from purified populations of macrophage and dendritic cells, a functionally related cell type. Sequence analysis revealed a high incidence of novel mRNAs within these cDNA libraries. These studies provide insights into the depths of transcriptional complexity still untapped amongst products of inducible genes, and identify macrophage and dendritic cell populations as a starting point for s ling the inducible mammalian transcriptome.
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.MOLCEL.2019.05.024
Abstract: Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 24 hippoc al neurons with three distinct single-cell genomic approaches, we characterized and validated a somatic L1 insertion bearing a 3' transduction. The source (donor) L1 for this insertion was slightly 5' truncated, lacked the YY1 binding site, and was highly mobile when tested in vitro. Locus-specific bisulfite sequencing revealed that the donor L1 and other young L1s with mutated YY1 binding sites were hypomethylated in embryonic stem cells, during neurodifferentiation, and in liver and brain tissue. These results explain how L1 can evade repression and retrotranspose in the human body.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Cold Spring Harbor Laboratory
Date: 30-05-2021
DOI: 10.1101/2021.05.28.446065
Abstract: A recent study proposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we applied deep ( ×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2, and did not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolved 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV) positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions via ONT sequencing. That we found no evidence of SARS-CoV-2 integration suggests such events are, at most, extremely rare in vivo , and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.
Publisher: Elsevier BV
Date: 04-2015
Publisher: Public Library of Science (PLoS)
Date: 03-2018
Publisher: Oxford University Press (OUP)
Date: 15-07-2009
DOI: 10.1093/BIOINFORMATICS/BTP438
Abstract: Summary: Multi-mapping sequence tags are a significant impediment to short-read sequencing platforms. These tags are routinely omitted from further analysis, leading to experimental bias and reduced coverage. Here, we present MuMRescueLite, a low-resource requirement version of the MuMRescue software that has been used by several next generation sequencing projects to probabilistically reincorporate multi-mapping tags into mapped short read data. Availability and implementation: MuMRescueLite is written in Python executables and documentation are available from genome.gsc.riken.jp/osc/english/software/. Contact: geoff.faulkner@roslin.ed.ac.uk
Publisher: Elsevier BV
Date: 2007
Publisher: Cold Spring Harbor Laboratory
Date: 10-08-2021
DOI: 10.1101/2021.08.09.455753
Abstract: We present Nanopore-DamID, a method to simultaneously detect cytosine methylation and DNA-protein interactions from single molecules, via selective sequencing of adenine-labelled DNA. Assaying LaminB1 and CTCF binding with Nanopore-DamID, we identify escape from LAD-associated repression of hypomethylated promoters amidst generalised hypermethylation of LaminB1-associated regulatory elements. We detect novel CTCF binding sites in highly repetitive regions, and allele-specific CTCF binding to imprinted genes and the active X chromosome. Nanopore-DamID highlights the importance of DNA methylation to transcription factor activity.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.NEUROBIOLAGING.2021.07.010
Abstract: Somatic mutations arise randomly or are induced by environmental factors, which may increase the risk of Alzheimer's disease (AD). Identifying somatic mutations in sporadic AD (SAD) may provide new insight of the disease. To evaluate the potential contribution of somatic single nucleotide variations (SNVs), particularly that of well-known AD-candidate genes, we investigated sequencing data sets from four platforms: whole-genome sequencing (WGS), deep whole-exome sequencing (WES) on paired brain and liver s les, RNA sequencing (RNA-seq), and single-cell whole-genome sequencing (scWGS) of brain s les from 16 AD patients and 16 non-AD in iduals. We found that the average number, mean variant allele fractions (VAFs) and mutational signatures of somatic SNVs have similar distributions between AD brains and non-AD brains. We did not identify any somatic SNVs within coding regions of the APP, PSEN1, PSEN2, nor in APOE. This study shows that somatic SNVs within the coding region of AD-candidate genes are unlikely to be a common causal factor for SAD.
Publisher: Wiley
Date: 06-04-2011
DOI: 10.1016/J.FEBSLET.2011.03.061
Abstract: Mobile genetic elements feature prominently in mammalian genome evolution. Several transposition-competent retrotransposon families (L1, Alu, SVA) remain active in the human germ line, leading to pathogenesis as well as genome structural variation across the global population. High-throughput screening approaches have recently been developed to detect retrotransposon insertion polymorphisms. Evidence produced by these and other genome-scale technologies indicates an expanded role for retrotransposition in human biology, including somatic mobilisation in the developing embryo and in neural cells.
Location: Australia
Location: Australia
Start Date: 2017
End Date: 12-2018
Amount: $275,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2020
End Date: 12-2023
Amount: $546,992.00
Funder: Australian Research Council
View Funded Activity