scholarly journals Analysis of EST-Driven Gene Annotation in Human Genomic Sequence

1998 ◽  
Vol 8 (4) ◽  
pp. 362-376 ◽  
Author(s):  
L. Charles Bailey ◽  
David B. Searls ◽  
G. Christian Overton
2019 ◽  
Vol 48 (1) ◽  
pp. 472-485 ◽  
Author(s):  
Felix Lansing ◽  
Maciej Paszkowski-Rogacz ◽  
Lukas Theo Schmitt ◽  
Paul Martin Schneider ◽  
Teresa Rojo Romanos ◽  
...  

Abstract Site-specific recombinases (SSRs) such as the Cre/loxP system are useful genome engineering tools that can be repurposed by altering their DNA-binding specificity. However, SSRs that delete a natural sequence from the human genome have not been reported thus far. Here, we describe the generation of an SSR system that precisely excises a 1.4 kb fragment from the human genome. Through a streamlined process of substrate-linked directed evolution we generated two separate recombinases that, when expressed together, act as a heterodimer to delete a human genomic sequence from chromosome 7. Our data indicates that designer-recombinases can be generated in a manageable timeframe for precision genome editing. A large-scale bioinformatics analysis suggests that around 13% of all human protein-coding genes could be targetable by dual designer-recombinase induced genomic deletion (dDRiGD). We propose that heterospecific designer-recombinases, which work independently of the host DNA repair machinery, represent an efficient and safe alternative to nuclease-based genome editing technologies.


2002 ◽  
Vol 12 (3) ◽  
pp. 424-429 ◽  
Author(s):  
C. A.M. Semple ◽  
S. W. Morris ◽  
D. J. Porteous ◽  
K. L. Evans

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153338 ◽  
Author(s):  
Miki Fukuma ◽  
Yuto Ganmyo ◽  
Osamu Miura ◽  
Takashi Ohyama ◽  
Noriaki Shimizu

1999 ◽  
Vol 15 (7) ◽  
pp. 284-286 ◽  
Author(s):  
Wonhee Jang ◽  
Hsiu-Chuan Chen ◽  
Hugues Sicotte ◽  
Gregory D. Schuler

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Galia R. Zimerman ◽  
Dina Svetlitsky ◽  
Meirav Zehavi ◽  
Michal Ziv-Ukelson

AbstractGene clusters are groups of genes that are co-locally conserved across various genomes, not necessarily in the same order. Their discovery and analysis is valuable in tasks such as gene annotation and prediction of gene interactions, and in the study of genome organization and evolution. The discovery of conserved gene clusters in a given set of genomes is a well studied problem, but with the rapid sequencing of prokaryotic genomes a new problem is inspired. Namely, given an already known gene cluster that was discovered and studied in one genomic dataset, to identify all the instances of the gene cluster in a given new genomic sequence. Thus, we define a new problem in comparative genomics, denoted PQ-Tree Search that takes as input a PQ-tree T representing the known gene orders of a gene cluster of interest, a gene-to-gene substitution scoring function h, integer arguments $$d_T$$ d T and $$d_S$$ d S , and a new sequence of genes S. The objective is to identify in S approximate new instances of the gene cluster; These instances could vary from the known gene orders by genome rearrangements that are constrained by T, by gene substitutions that are governed by h, and by gene deletions and insertions that are bounded from above by $$d_T$$ d T and $$d_S$$ d S , respectively. We prove that PQ-Tree Search is -hard and propose a parameterized algorithm that solves the optimization variant of PQ-Tree Search in $$O^*(2^{\gamma })$$ O ∗ ( 2 γ ) time, where $$\gamma$$ γ is the maximum degree of a node in T and $$O^*$$ O ∗ is used to hide factors polynomial in the input size. The algorithm is implemented as a search tool, denoted PQFinder, and applied to search for instances of chromosomal gene clusters in plasmids, within a dataset of 1,487 prokaryotic genomes. We report on 29 chromosomal gene clusters that are rearranged in plasmids, where the rearrangements are guided by the corresponding PQ-trees. One of these results, coding for a heavy metal efflux pump, is further analysed to exemplify how PQFinder can be harnessed to reveal interesting new structural variants of known gene clusters.


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