scholarly journals Identification of the Telomere elongation mutation in Drosophila

2018 ◽  
Author(s):  
Hemakumar M. Reddy ◽  
Thomas A. Randall ◽  
Radmila Capkova Frydrychova ◽  
James M. Mason
Keyword(s):  
Drosophila Melanogaster ◽  
Next Generation Sequencing ◽  
Ltr Retrotransposons ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Telomere Elongation ◽  
Drosophila Genetic Reference Panel ◽  
Generation Sequencing

Background. Telomeres in Drosophila melanogaster are similar to those of other eukaryotes in terms of their function, although they are formed by non-LTR retrotransposons instead of telomerase-based short repeats. The length of the telomeres in Drosophila depends on the number of copies of these transposable elements. A dominant mutation, Tel1, causes a several-fold elongation of telomeres. Methods. In this study we identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next generation sequencing. Results. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Discussion. The mapped Tel1 mutation (3-bp deletion found in Ino80) did not appear to affect the quantity or length of the Ino80 transcript. Tel1 causes a significant reduction in transcripts of CG18493, a gene nested in an intron 8 of Ino80, which is expressed in ovaries and expected to encode a serine-type peptidase.

scholarly journals Identification of the Telomere elongation mutation in Drosophila

2018 ◽  
Author(s):  
Hemakumar M. Reddy ◽  
Thomas A. Randall ◽  
Radmila Capkova Frydrychova ◽  
James M. Mason
Keyword(s):  
Drosophila Melanogaster ◽  
Next Generation Sequencing ◽  
Ltr Retrotransposons ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Telomere Elongation ◽  
Drosophila Genetic Reference Panel ◽  
Generation Sequencing

Background. Telomeres in Drosophila melanogaster are similar to those of other eukaryotes in terms of their function, although they are formed by non-LTR retrotransposons instead of telomerase-based short repeats. The length of the telomeres in Drosophila depends on the number of copies of these transposable elements. A dominant mutation, Tel1, causes a several-fold elongation of telomeres. Methods. In this study we identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next generation sequencing. Results. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Discussion. The mapped Tel1 mutation (3-bp deletion found in Ino80) did not appear to affect the quantity or length of the Ino80 transcript. Tel1 causes a significant reduction in transcripts of CG18493, a gene nested in an intron 8 of Ino80, which is expressed in ovaries and expected to encode a serine-type peptidase.

scholarly journals Complete Genome Sequences of Six Measles Virus Strains

2018 ◽  
Vol 6 (13) ◽  
Author(s):  
My V. T. Phan ◽  
Claudia M. E. Schapendonk ◽  
Bas B. Oude Munnink ◽  
Marion P. G. Koopmans ◽  
Rik L. de Swart ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Complete Genome ◽  
Measles Virus ◽  
Genetic Characterization ◽  
Critical Component ◽  
Wild Type ◽  
Genome Sequences ◽  
Virus Strains ◽  
Generation Sequencing

ABSTRACT Genetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing.

Characterization of Holliday structures in FLP protein-promoted site-specific recombination

1990 ◽  
Vol 10 (1) ◽  
pp. 235-242
Author(s):  
L Meyer-Leon ◽  
R B Inman ◽  
M M Cox
Keyword(s):  
Reaction Rate ◽  
Reaction Pathway ◽  
Reaction Intermediates ◽  
Wild Type ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Isomerization Process ◽  
Previous Demonstration ◽  
Rate Limiting

Holliday structures are formed in the course of FLP protein-promoted site-specific recombination. Here, we demonstrate that Holliday structures are formed in reactions involving wild-type substrates and that they are kinetically competent with respect to the overall reaction rate. Together with a previous demonstration of chemical competence (L. Meyer-Leon, L.-C. Huang, S. W. Umlauf, M. M. Cox, and R. B. Inman, Mol. Cell. Biol. 8:3784-3796, 1988), Holliday structures therefore meet all criteria necessary to establish that they are obligate reaction intermediates in FLP-mediated site-specific recombination. In addition, kinetic evidence suggests that two distinct forms of the Holliday intermediate are present in the reaction pathway, interconverted in an isomerization process that is rate limiting at 0 degree C.

Analysis of correlation between oncogene mutation and response to chemotherapy in all RAS wild type metastatic colorectal cancer, using next-generation sequencing technology.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 553-553
Author(s):  
Akio Higuchi ◽  
Rika Kasajima ◽  
Manabu Shiozawa ◽  
Masahiro Asari ◽  
Masaaki Murakawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Driver Mutations ◽  
Wild Type ◽  
Sequencing Technology ◽  
Mutation Status ◽  
Next Generation Sequencing Technology ◽  
Response Group ◽  
Generation Sequencing ◽  
Kras Mutation Status

553 Background: Targeted therapies of monoclonal antibodies have changed the treatment of metastatic colorectal cancer (mCRC). A target therapy with chemotherapy regimen for mCRC was decided by KRAS mutation status (KRAS exon2 [codon12, codon13]). Currently, there are many reports suggesting that in addition to analysis of KRAS mutation status, the evaluation of EGFR gene copy number, levels of EGFR ligands, BRAF, NRAS, PIK3CA mutations could be helpful to have a more accurate selection of patients who may have a benefit from anti-EGFR targeted drugs. Methods: Mutation status of 50 oncogenes were analysed in 35 mCRC patients with all RAS wild type, using next-generation sequencing technology. The response for chemotherapy was classified response group (R group) and non-response group (N group) by RECIST. The relation between mutation status of 50 oncogenes and the response for chemotherapy was assessed. Results: There were 25 oncogene mutations in the 50 genes. Driver mutation associated with oncogenic mutation deeply were 5 oncogenes, which were PIK3CA, AKT1, BRAF, PDGFRA and TP53. Only BRAF mutation was significantly associated with poor chemo response in the 5 oncogenes. A case which had two driver mutations was only in the N group. One of the two driver mutations was tumor suppressor gene, TP53. Conclusions: BRAF mutation and the number of driver mutations are key predictors of chemosensitivity in the mCRC cases with all RAS wild type.

Therapeutic impact and timing of gastrointestinal malignancy genomic profiling: A single-institution experience.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 584-584
Author(s):  
Kristin Lynn Koenig ◽  
Jarred Burkart ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
Anne M. Noonan ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Clinical Care ◽  
Comprehensive Cancer Center ◽  
Genomic Profiling ◽  
Next Generation ◽  
Wild Type ◽  
Genomic Alterations ◽  
Generation Sequencing

584 Background: Tumor genomic profiling has become critical in the identification of targeted therapeutic options for patients (pts) with advanced malignancies. Mutational frequencies and their therapeutic importance vary among tumor types. This analysis was undertaken to characterize the landscape of genomic alterations in gastrointestinal (GI) malignancies found in a large academic institutional practice, and to determine the frequency of alteration-specific targeted therapy selection based on genomic profiling. Methods: Adult pts with GI malignancies presenting to the Ohio State University Comprehensive Cancer Center oncology clinics were offered next generation sequencing through FoundationOne testing as part of routine clinical care. Institutional review board approval was obtained to retrospectively analyze results from FoundationOne testing performed between 2012 and 2015. Results: 265 pts with GI malignancies underwent successful genomic profiling. 1205 genomic alterations were found, with an average of 4.5 per tumor (range 0-20); 365 (30%) of these were potentially actionable and most often found in colorectal or gastroesophageal tumors. 14 pts (5.3%) had actionable alterations in MET, CDKN2A/B, FGFR2, KRAS, BRAF, or NF2 that led to enrollment in genotype-directed clinical trials or off label use of targeted therapies beyond standard of care. Pt performance status at the time of genomic alteration identification was a significant factor in precluding genotype-directed therapy. One variant of unknown significance involving FGFR2 identified at initial testing subsequently became actionable and led to pt enrollment on a clinical trial. One pt with rectal cancer was found to have a KRAS wild-type and BRAF mutant primary but KRAS mutant and BRAF wild-type liver metastasis. Conclusions: Genomic profiling of GI malignancies through next generation sequencing is feasible and can lead to genotype-directed therapy selection; however, it should be considered early in the pt’s course to optimize use of targeted therapies through clinical trials. Consideration should be given to serial tumor testing to identify emerging genomic alterations for optimal therapy selection.

Somatic POLE proofreading domain mutations by next generation sequencing to predict outcomes in stage II colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 559-559
Author(s):  
Shaobo Mo ◽  
Yaqi Li ◽  
Junjie Peng
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Molecular Heterogeneity ◽  
Next Generation ◽  
Wild Type ◽  
Mutation Status ◽  
Pathologic Features ◽  
Generation Sequencing

559 Background: Stage II colorectal cancers (CRC) exhibit unique molecular heterogeneity and patients with somatic POLE mutations are defined as a distinct tumor subgroup. The aim of this study was to clarify the characteristics and prognostic effect of somatic POLE proofreading domain mutations by Next Generation Sequencing in stage II CRC. Methods: Recurrent patients were 1:1 matched to patient with no recurrence for stage II CRC patients diagnosed between 2008 and 2013 in Fudan University Shanghai Cancer Center (FUSCC). All patients were pathologically confirmed and received radical resection. Microsatellite instability status and POLE mutation status were determined by NGS using ColonCore panel (Burning Rock, Guangzhou, China). Groups based on NGS-POLE mutation status were compared in terms of patient demographics and pathologic features using chi-squared tests. Survival curves were plotted using the Kaplan-Meier method. Results: In total, 245 stage II CRC patients were enrolled. POLE mutations were detected in 25 (10.2%) of 245 stage II CRC, while only 9 (3.7%) was located in proofreading domain (NGS-POLE EDM-mutations) and other 16 were found in non-proofreading domain (non-NGS-POLE mutations). Compared to cases with wild-type POLE, cases with NGS-POLE EDM-mutations were more prone to be microsatellite instability-high (MSI-H) (3 of 9 [33.3%] vs. 23 of 236 [9.7%], p = 0.024), younger at diagnosis (median 46 years vs. 62 years, p < 0.001), and more frequently with right-sided tumor location (6 of 9 [66.7%] vs. 54 of 236 [22.9%]; p = 0.003). All tumors with NGS-POLE EDM-mutations presented with a surprisingly high tumor mutation burden (TMB) (median 145.2 per Mb). Patients with NGS-POLE EDM-mutations have favorable 5-year disease-free survival (DFS) compared with those with non-NGS-POLE EDM-mutations and wild-type POLE (100% vs. 62.5% vs. 52.5%, p = 0.037). Though there is DFS difference between patients with non-NGS-POLE EDM-mutations and wild-type POLE, the difference was not statistically significant (p = 0.412). Conclusions: Stage II CRC patients with NGS-POLE EDM-mutation identify a special cancer subset with better immune environment predicting excellent outcomes.

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