Targeted Metabolic Engineering Guided by Computational Analysis of Single-Nucleotide Polymorphisms (SNPs)

2013 ◽  
pp. 409-428
Author(s):  
D. B. R. K. Gupta Udatha ◽  
Simon Rasmussen ◽  
Thomas Sicheritz-Pontén ◽  
Gianni Panagiotou
Keyword(s):  
Metabolic Engineering ◽  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Prediction of Structural and Functional Effects of Single Nucleotide Polymorphisms in <i>NAT2</i>gene, a Computational Analysis

2019 ◽  
Vol 7 (4) ◽  
pp. 88
Author(s):  
Amna Elsadig Elsafi Abodlaa ◽  
Dalia Mursi ◽  
Mona Abdelrahman Mohamed Khaier ◽  
Mai Abdul RahmanMasri ◽  
Nazik Elmalaika Obaid Seid Ahmed Husain ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Computational analysis of functional single nucleotide polymorphisms associated with SLC26A4 gene

PLoS ONE ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. e0225368
Author(s):  
Mirza Jawad Ul Hasnain ◽  
Muhammad Shoaib ◽  
Salman Qadri ◽  
Bakhtawar Afzal ◽  
Tehreem Anwar ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Slc26a4 Gene

scholarly journals Genome Stability in Engineered Strains of the Extremely Thermophilic Lignocellulose-Degrading Bacterium Caldicellulosiruptor bescii

2017 ◽  
Vol 83 (14) ◽  
Author(s):  
Amanda M. Williams-Rhaesa ◽  
Farris L. Poole ◽  
Jessica T. Dinsmore ◽  
Gina L. Lipscomb ◽  
Gabriel M. Rubinstein ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Background ◽  
Genome Stability ◽  
Plant Biomass ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Content Type ◽  
Targeted Deletion ◽  
Caldicellulosiruptor Bescii

ABSTRACT Caldicellulosiruptor bescii is the most thermophilic cellulose degrader known and is of great interest because of its ability to degrade nonpretreated plant biomass. For biotechnological applications, an efficient genetic system is required to engineer it to convert plant biomass into desired products. To date, two different genetically tractable lineages of C. bescii strains have been generated. The first (JWCB005) is based on a random deletion within the pyrimidine biosynthesis genes pyrFA, and the second (MACB1018) is based on the targeted deletion of pyrE, making use of a kanamycin resistance marker. Importantly, an active insertion element, ISCbe4, was discovered in C. bescii when it disrupted the gene for lactate dehydrogenase (ldh) in strain JWCB018, constructed in the JWCB005 background. Additional instances of ISCbe4 movement in other strains of this lineage are presented herein. These observations raise concerns about the genetic stability of such strains and their use as metabolic engineering platforms. In order to investigate genome stability in engineered strains of C. bescii from the two lineages, genome sequencing and Southern blot analyses were performed. The evidence presented shows a dramatic increase in the number of single nucleotide polymorphisms, insertions/deletions, and ISCbe4 elements within the genome of JWCB005, leading to massive genome rearrangements in its daughter strain, JWCB018. Such dramatic effects were not evident in the newer MACB1018 lineage, indicating that JWCB005 and its daughter strains are not suitable for metabolic engineering purposes in C. bescii. Furthermore, a facile approach for assessing genomic stability in C. bescii has been established. IMPORTANCE Caldicellulosiruptor bescii is a cellulolytic extremely thermophilic bacterium of great interest for metabolic engineering efforts geared toward lignocellulosic biofuel and bio-based chemical production. Genetic technology in C. bescii has led to the development of two uracil auxotrophic genetic background strains for metabolic engineering. We show that strains derived from the genetic background containing a random deletion in uracil biosynthesis genes (pyrFA) have a dramatic increase in the number of single nucleotide polymorphisms, insertions/deletions, and ISCbe4 insertion elements in their genomes compared to the wild type. At least one daughter strain of this lineage also contains large-scale genome rearrangements that are flanked by these ISCbe4 elements. In contrast, strains developed from the second background strain developed using a targeted deletion strategy of the uracil biosynthetic gene pyrE have a stable genome structure, making them preferable for future metabolic engineering studies.

scholarly journals Computational Analysis of Single Nucleotide Polymorphisms Associated with Altered Drug Responsiveness in Type 2 Diabetes

2016 ◽  
Vol 17 (7) ◽  
pp. 1008 ◽  
Author(s):  
Valerio Costa ◽  
Antonio Federico ◽  
Carla Pollastro ◽  
Carmela Ziviello ◽  
Simona Cataldi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Drug Responsiveness

Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene

Gene Reports ◽  
2017 ◽  
Vol 6 ◽  
pp. 142-157 ◽  
Author(s):  
Nitin Chitranshi ◽  
Yogita Dheer ◽  
Roshana Vander Wall ◽  
Veer Gupta ◽  
Mojdeh Abbasi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Computational Analysis of Functional Single Nucleotide Polymorphisms Associated with the CYP11B2 Gene

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e104311 ◽  
Author(s):  
Minyue Jia ◽  
Boyun Yang ◽  
Zhongyi Li ◽  
Huiling Shen ◽  
Xiaoxiao Song ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Computational Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Computational Analysis of Damaging Single-Nucleotide Polymorphisms and Their Structural and Functional Impact on the Insulin Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Zabed Mahmud ◽  
Syeda Umme Fahmida Malik ◽  
Jahed Ahmed ◽  
Abul Kalam Azad
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Insulin Receptor ◽  
Computational Analysis ◽  
Single Amino Acid ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Single Nucleotide ◽  
Complex Disorders ◽  
Functional Variants ◽  
And Function

Single-nucleotide polymorphisms (SNPs) associated with complex disorders can create, destroy, or modify protein coding sites. Single amino acid substitutions in the insulin receptor (INSR) are the most common forms of genetic variations that account for various diseases like Donohue syndrome or Leprechaunism, Rabson-Mendenhall syndrome, and type A insulin resistance. We analyzed the deleterious nonsynonymous SNPs (nsSNPs) in INSR gene based on different computational methods. Analysis of INSR was initiated with PROVEAN followed by PolyPhen and I-Mutant servers to investigate the effects of 57 nsSNPs retrieved from database of SNP (dbSNP). A total of 18 mutations that were found to exert damaging effects on the INSR protein structure and function were chosen for further analysis. Among these mutations, our computational analysis suggested that 13 nsSNPs decreased protein stability and might have resulted in loss of function. Therefore, the probability of their involvement in disease predisposition increases. In the lack of adequate prior reports on the possible deleterious effects of nsSNPs, we have systematically analyzed and characterized the functional variants in coding region that can alter the expression and function of INSR gene. In silico characterization of nsSNPs affecting INSR gene function can aid in better understanding of genetic differences in disease susceptibility.

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