A5047254032- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- T-cell and Retrovirus Studies
- Tissue Engineering and Regenerative Medicine
- CRISPR and Genetic Engineering
- Plant Virus Research Studies
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Circular RNAs in diseases
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Herpesvirus Infections and Treatments
- T-cell and B-cell Immunology
- Bacteriophages and microbial interactions
- Cancer-related molecular mechanisms research
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Viral Infections and Immunology Research
- Genomics and Phylogenetic Studies
- Animal Genetics and Reproduction
Johns Hopkins Medicine
2010-2021
Johns Hopkins University
2011-2021
Sidney Kimmel Comprehensive Cancer Center
2014
Johns Hopkins Hospital
2014
High Throughput Biology (United States)
2010-2014
Significance Repetitive sequences comprise a large portion of the genome and are often thought as “junk DNA.” They significant source genetic variation, particularly Alu elements. Their functional consequence is frequently dismissed. Here, we test hypothesis that polymorphisms contribute to phenotypic differences between individuals. We identified an enrichment in regions associated with human disease risk. Further, find 44 instances where trait-associated SNP surrogate for presence or...
Significance Much of our genome is repetitive sequence. This property poses challenges for investigators because differences in sequences are difficult to detect. With hundreds thousands similar repeats, it has been discern how one person’s differs from another or tumor DNA normal DNA. To solve this issue, we developed methods target next-generation sequencing the insertion sites most variable repeats. Computational pipelines make these studies scalable and more widely accessible were...
RNA splicing is a highly regulated process dependent on sequences near splice sites. Insertions of Alu retrotransposons can disrupt sites or bind regulators. We hypothesized that some common inherited polymorphic insertions are responsible for QTLs (sQTL). focused intronic variants mapping within 100 bp an alternatively used exon and screened those alter splicing. identify five loci, 21.7% assayed, where the alters While in most cases promotes skipping, at one locus increases inclusion. Of...
Long interspersed element-1 (LINE-1, L1) is the major driver of mobile DNA activity in modern humans. When expressed, LINE-1 loci produce bicistronic transcripts encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Many types human cancers are characterized by L1 promoter hypomethylation, transcription, protein expression, somatic retrotransposition. ORF2p encodes endonuclease reverse transcriptase activities required Its expression poorly tissues cell lines.We report...
Alu are high copy number interspersed repeats that have accumulated near genes during primate and human evolution. They a pervasive source of structural variation in modern humans. Impacts insertions may on gene expression not well understood, although some been associated with quantitative trait loci (eQTLs). Here, we directly test regulatory effects polymorphic isolation other variants the same haplotype. To screen insertion for those such effects, used ectopic luciferase reporter assays...
Abstract Background Mobile elements are a major source of structural variants in the human genome, and some mobile can regulate gene expression transcript splicing. However, impact polymorphic element insertions (pMEIs) on splicing diverse tissues has not been thoroughly studied. The multi-tissue whole genome sequencing data generated by Genotype-Tissue Expression (GTEx) project provide great opportunity to systematically evaluate role pMEIs regulating tissues. Results Using GTEx data, we...
A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) anti-sera and PCR, we determined if additional or other lines contain XMRV MLV-related viruses. Our study included total 72 lines, which 58 60 human used anticancer drug screens maintained at NCI-Frederick (NCI-60). We have identified gammaretroviruses two lines: LAPC4...
Transposable elements make up a significant portion of the human genome. Accurately locating these mobile DNAs is vital to understand their role as source structural variation and somatic mutation. To this end, laboratories have developed strategies selectively amplify or otherwise enrich transposable element insertion sites in genomic DNA. Here we describe technique, Transposon Insertion Profiling by sequencing (TIPseq), map Long INterspersed Element 1 (LINE-1, L1) retrotransposon...
Gliomas are the most common primary brain tumors in adults. We sought to understand roles of endogenous transposable elements these malignancies by identifying evidence somatic retrotransposition glioblastomas (GBM). performed transposon insertion profiling active subfamily Long INterspersed Element-1 (LINE-1) deep sequencing (TIPseq) on genomic DNA low passage oncosphere cell lines derived from 7 GBM biopsies, 3 secondary tissue samples, and matched normal intravenous blood samples same...
Polymorphic Alu elements account for 17% of structural variants in the human genome. The majority these belong to youngest AluY subfamilies, and most variant discovery efforts have focused on identifying polymorphisms from currently retrotranspositionally active subfamilies. In this report we analyze evolutionarily older AluS subfamily, whose peak activity was tens millions years ago. We annotate polymorphisms, assess their likely mechanism origin, evaluate contribution variation Of 52...
Abstract Background Lymphocytes achieve diversity in antigen recognition part by rearranging genomic DNA at loci encoding antibodies and cell surface receptors. The process, termed V(D)J recombination, juxtaposes modular coding sequences for binding. Erroneous recombination events causing chromosomal translocations are recognized causes of lymphoid malignancies. Here we show a hybridization based method sequence enrichment can be used to efficiently selectively capture adjacent breakpoints...
Long interspersed element-1 (LINE-1, L1) sequences, which comprise about 17% of human genome, are the product one most active types mobile DNAs in modern humans. LINE-1 insertion alleles can cause inherited and de novo genetic diseases, LINE-1-encoded proteins highly expressed some cancers. Genome-wide mapping single cells could be useful for defining somatic germline retrotransposition rates, enabling studies to characterize tumour heterogeneity, relate insertions transcriptional epigenetic...
Abstract Motivation: Repetitive sequences account for approximately half of the human genome. Accurately ascertaining in these regions with next generation sequencers is challenging, and requires a different set analytical techniques than reads originating from unique sequences. Complicating matter are repetitive subject to programmed rearrangements, as case antigen-binding domains Immunoglobulin (Ig) T-cell receptor (TCR) loci. Results: We developed probability-based score visualization...
A bstract Background Long interspersed element-1 (LINE-1, L1) is the major driver of mobile DNA activity in modern humans. When expressed, LINE-1 loci produce bicistronic transcripts encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Many types human cancers are characterized by L1 promoter hypomethylation, transcription, protein expression, somatic retrotransposition. ORF2p encodes endonuclease reverse transcriptase activities required Its expression poorly tissues...
Abstract Background Mobile elements are a major source of human structural variants and some mobile can regulate gene expression alternative splicing. However, the impact polymorphic element insertions (pMEIs) on splicing in diverse tissues has not been thoroughly studied. The multi-tissue whole genome sequencing data generated by Genotype-Tissue Expression (GTEx) project provide great opportunity to systematic determine pMEIs’ role regulation tissues. Results Using GTEx data, we identified...