Rapid mapping of Escherichia coli::Tn5 insertion mutations by REP-Tn5 PCR.

PCR Methods Appl

Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030.

Published: February 1992

We describe a novel method to map chromosomal Escherichia coli::Tn5 insertion mutations rapidly. This method utilizes the ends of Tn5 and the E. coli REP sequence as primer binding sites for the polymerase chain reaction (PCR). The unique E. coli chromosomal sequence located between these primer binding sites is amplified by PCR and used as a probe to identify the recombinant clones from the Kohara phage ordered E. coli miniset bank that contains the Tn5 mutated loci. We used this approach to map two Tn5 insertion mutations previously identified by their effect on glycerol metabolism. The insertion mutations mapped to glpD, the aerobic sn-glycerol-3-phosphate dehydrogenase gene. Phenotypic analysis of the mutant strains revealed one with partial GlpD activity, suggesting transposon-mediated alteration of promoter activity. This mapping method should be applicable to the rapid physical mapping of any insertion mutation in the E. coli chromosome.

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.1.3.187DOI Listing

Publication Analysis

Top Keywords

insertion mutations
16
escherichia colitn5
8
colitn5 insertion
8
primer binding
8
binding sites
8
insertion
5
rapid mapping
4
mapping escherichia
4
mutations
4
mutations rep-tn5
4

Similar Publications

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

J Med Chem

January 2025

Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

View Article and Find Full Text PDF

Background: Limited information is available regarding the clinical features and outcomes of advanced human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) in Taiwan, despite expanding treatment options for this distinct subtype. The present study explored the clinical features and outcomes of HER2-mutant NSCLC in a real-world setting.

Methods: Relevant data were collected from patients with advanced or recurrent HER2-mutant NSCLC who received systemic therapy between 2011 and 2021 and were followed up until 2022 at two medical centers in Taiwan.

View Article and Find Full Text PDF

In our study, we aimed to identify new mutants resulting from ONSEN transposition in Arabidopsis thaliana by subjecting nrpd1 mutants to heat stress. We isolated a mutant with a significantly elongated hypocotyl, named "Long hypocotyl in ONSEN inserted line 1" (HYO1). This phenotype was heritable, with progeny consistently displaying longer hypocotyls than the wild type.

View Article and Find Full Text PDF

Light chain Split Luciferase assay implicates pathological NOTCH3 thiol reactivity in inherited cerebral small vessel disease.

J Biol Chem

January 2025

Departments of Neurology, University of Michigan, Ann Arbor, MI 48109; Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109; Neurology Service, VA Ann Arbor Healthcare System, Department of Veterans Affairs, Ann Arbor, MI 48105. Electronic address:

Stereotyped mutations in NOTCH3 drive CADASIL, the leading inherited cause of stroke and vascular dementia. The vast majority of these mutations result in alterations in the number of cysteines in the gene product. However, non-cysteine altering pathogenic mutations have also been identified, making it challenging to discriminate pathogenic from benign NOTCH3 sequence variants.

View Article and Find Full Text PDF

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Dev Cell

January 2025

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!