scholarly journals Computational Analysis of the Sequences of LIPE Gene of Selected Ruminants and Non-ruminants

2019 ◽  
pp. 1-10
Author(s):  
Rasheed B. Fatai ◽  
Mabel O. Akinyemi ◽  
Osamede Henry Osaiyuwu
Keyword(s):  
Amino Acid ◽  
Protein Kinase ◽  
Water Buffalo ◽  
Nucleotide Sequences ◽  
Molecular Techniques ◽  
Farm Animals ◽  
Mass Selection ◽  
Amino Acid Substitutions ◽  
Sequencing Analysis ◽  
Single Nucleotide

Tropically adapted farm animals are characterized by low meat and milk productivity. Traditionally, mass selection has been widely employed in breeding for improved animal performance. However, improving animal productivity using mass selection is laborious and usually less effective. Advances in molecular techniques such as DNA sequencing analysis provide the opportunity to characterize meat and milk influencing genes, which can lead to faster genetic improvement but often unaffordable and expensive particularly in developing countries. Unlike the wet laboratory analysis, computational molecular analyses is comparatively cheaper in pre-screening of the functional impacts of nonsynonymous single-nucleotide variants of some performance traits-related genes such as hormone-sensitive lipase (LIPE). A total of fifteen (15) LIPE nucleotide sequences comprising pig (3), cattle (3), water buffalo (2), camel (2), goat (2) and sheep (3) were retrieved from the Genbank. Also, twenty (20) functionally associated genes with the LIPE gene including perilipin 1, 2 & 5 protein kinase cAMP-activated catalytic subunit alpha, protein kinase X-linked were determined using the GeneMANIA. Functional analysis of non-synonymous single nucleotide polymorphism using PROVEAN showed that ten amino acid substitutions (S216C, P107del, Q28_P29insRATHVA, S41_S44dup, A640M, S940A, L660I,  D86delinsWA, S1000F) in water buffalo and pig (X678E, V789K, G987del, T218K, Q2234del, L278H, Q321del, L1023delinsPKL, P1452V, H1267delinsRFT), nine in sheep (F67_P68delinsVQ, R24G, A247_R248dup, L122L, L144P, S149K, S125S,  S224H, G148M) and goats (A450Y, P480H, G490delinsPHQ, L500R, R550del, S100_S101dup, E600S, A700Q, P754delinsQAW) and five in camel (A320A, S210S, L130L, T400T, L440I) were found neutral indicating their beneficial effect while only T110A out of the fifteen amino acid substitutions was found deleterious in cattle. The obtained phylogenetic trees from the nucleotide sequences showed a closer relationship among the members of the Bovidae family particularly the sheep and cattle. This information may aid future research that aims at the selection of the studied animals for improved meat and milk quality traits.

scholarly journals Genotypic and Phenotypic Analyses of Hepatitis C Virus from Patients Treated with JTK-853 in a Three-Day Monotherapy

2012 ◽  
Vol 57 (1) ◽  
pp. 436-444 ◽  
Author(s):  
Naoki Ogura ◽  
Yukiyo Toyonaga ◽  
Izuru Ando ◽  
Kunihiro Hirahara ◽  
Tsutomu Shibata ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Viral Resistance ◽  
Hcv Rna ◽  
Amino Acid Substitutions ◽  
Sequencing Analysis ◽  
Resistance Mutations ◽  
In The Wild

ABSTRACTJTK-853, a palm site-binding NS5B nonnucleoside polymerase inhibitor, shows antiviral activityin vitroand in hepatitis C virus (HCV)-infected patients. Here, we report the results of genotypic and phenotypic analyses of resistant variants in 24 HCV genotype 1-infected patients who received JTK-853 (800, 1,200, or 1,600 mg twice daily or 1,200 mg three times daily) in a 3-day monotherapy. Viral resistance in NS5B was investigated using HCV RNA isolated from serum specimens from the patients. At the end of treatment (EOT) with JTK-853, the amino acid substitutions M414T (methionine [M] in position 414 at baseline was replaced with threonine [T] at EOT), C445R (cysteine [C] in position 445 at baseline was replaced with arginine [R] at EOT), Y448C/H (tyrosine [Y] in position 448 at baseline was replaced with cysteine [C] or histidine [H] at EOT), and L466F (leucine [L] in position 466 at baseline was replaced with phenylalanine [F] at EOT), which are known to be typical resistant variants of nonnucleoside polymerase inhibitors, were observed in a clonal sequencing analysis. These substitutions were also selected by a treatment with JTK-853in vitro, and the 50% effective concentration of JTK-853 in the M414T-, C445F-, Y448H-, and L466V-harboring replicons attenuated the susceptibility by 44-, 5-, 6-, and 21-fold, respectively, compared with that in the wild-type replicon (Con1). These findings suggest that amino acid substitutions of M414T, C445R, Y448C/H, and L466F are thought to be viral resistance mutations in HCV-infected patients receiving JTK-853 in a 3-day monotherapy.

Molecular Monitoring of Knockdown Resistance in Head Louse (Phthiraptera: Pediculidae) Populations in Iran

2021 ◽  
Author(s):  
Fereshteh Ghahvechi Khaligh ◽  
Navid Dinparast Djadid ◽  
Mostafa Farmani ◽  
Zahra Asadi Saatlou ◽  
Samira Frooziyan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Head Louse ◽  
Molecular Techniques ◽  
Common Mechanism ◽  
Amino Acid Substitutions ◽  
Head Lice ◽  
Knockdown Resistance ◽  
Resistance Mutations ◽  
Accurate Detection ◽  
Genotype Frequencies

Abstract Knockdown resistance (kdr) is a common mechanism of insecticide resistance in head lice to the conventionally used pyrethroid pediculosis and can be the result of various amino acid substitutions within the voltage-sensitive sodium channel (VSSC). In this study, 54 sequences from varied specimens were investigated to monitor well-known resistance mutations and probable new mutations. The Pediculus humanus capitis de Geer specimens were collected from 13 provinces in Iran. The specimens were stored in 70% ethanol until DNA extraction and PCR amplification of ~900-bp fragment of VSSC. The sequences were analyzed using different bioinformatics software for the detection of well-known kdr substitutions and additional mutations potentially associated with kdr resistance in head lice. There were six new and an old (haplotype I) kdr haplotypes within the Iranian head louse population. K794E, F815I, and N818D amino acid substitutions were reported for the first time. The P813H mutation was the most prevalent amino acid substitution in eight provinces. Among 53 sequences, 26 (49%) were homozygous susceptible, and 27 (51%) were heterozygotes. Thus, 51% of the head lice collected in Iran harbored only the P813H allele. The exact test for the Hardy–Weinberg (H–W) equilibrium showed that genotype frequencies differed significantly from the expectation in East-Azerbaijan and Tehran provinces. Moreover, these populations had an inbreeding coefficient (Fis) <0, indicating the excess of heterozygotes. This observation suggests that the populations of head lice from Iran are currently under active selective pressure. For the rest of the populations, H–W equilibrium and the expectations were significantly in harmony. The results of the current study highlight molecular techniques in the accurate detection of resistance genotypes before their establishment within the head louse population. Accurate detection of resistant genotypes seems to be helpful in decision-making on lice control programs and resistance monitoring and management.

A STRUCTURAL BIOINFORMATICS APPROACH TO THE ANALYSIS OF NONSYNONYMOUS SINGLE NUCLEOTIDE POLYMORPHISMS (nsSNPs) AND THEIR RELATION TO DISEASE

2007 ◽  
Vol 05 (06) ◽  
pp. 1297-1318 ◽  
Author(s):  
CATHERINE L. WORTH ◽  
G. RICHARD J. BICKERTON ◽  
ADRIAN SCHREYER ◽  
JULIA R. FORMAN ◽  
TAMMY M. K. CHENG ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Structure Prediction ◽  
Three Dimensional ◽  
Comparative Modeling ◽  
Divergent Evolution ◽  
Amino Acid Substitutions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Proteins

The prediction of the effects of nonsynonymous single nucleotide polymorphisms (nsSNPs) on function depends critically on exploiting all information available on the three-dimensional structures of proteins. We describe software and databases for the analysis of nsSNPs that allow a user to move from SNP to sequence to structure to function. In both structure prediction and the analysis of the effects of nsSNPs, we exploit information about protein evolution, in particular, that derived from investigations on the relation of sequence to structure gained from the study of amino acid substitutions in divergent evolution. The techniques developed in our laboratory have allowed fast and automated sequence-structure homology recognition to identify templates and to perform comparative modeling; as well as simple, robust, and generally applicable algorithms to assess the likely impact of amino acid substitutions on structure and interactions. We describe our strategy for approaching the relationship between SNPs and disease, and the results of benchmarking our approach — human proteins of known structure and recognized mutation.

scholarly journals Different Mutations in the Genome-Linked Protein VPg of Potato virus Y Confer Virulence on the pvr23 Resistance in Pepper

2006 ◽  
Vol 19 (5) ◽  
pp. 557-563 ◽  
Author(s):  
Valérie Ayme ◽  
Sylvie Souche ◽  
Carole Caranta ◽  
Mireille Jacquemond ◽  
Joël Chadœuf ◽  
...  
Keyword(s):  
Amino Acid ◽  
Genetic Drift ◽  
Potato Virus ◽  
High Frequency ◽  
Potato Virus Y ◽  
Relative Fitness ◽  
Amino Acid Substitutions ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Pepper Plants

Five different amino acid substitutions in the VPg of Potato virus Y were shown to be independently responsible for virulence toward pvr23 resistance gene of pepper. A consequence of these multiple mutations toward virulence involving single nucleotide substitutions is a particularly high frequency of resistance breaking (37% of inoculated plants from the first inoculation) and suggests a potentially low durability of pvr23 resistance. These five mutants were observed with significantly different frequencies, one of them being overrepresented. Genetic drift alone could not explain the observed distribution of virulent mutants. More plausible scenarios were obtained by taking into account either the relative substitution rates, the relative fitness of the mutants in pvr23 pepper plants, or both.

scholarly journals Sparfloxacin Resistance in Clinical Isolates ofStreptococcus pneumoniae: Involvement of Multiple Mutations in gyrA and parC Genes

1998 ◽  
Vol 42 (9) ◽  
pp. 2193-2196 ◽  
Author(s):  
Hideki Taba ◽  
Nobuchika Kusano
Keyword(s):  
Streptococcus Pneumoniae ◽  
Amino Acid ◽  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
Clinical Isolates ◽  
Amino Acid Substitutions ◽  
Sequencing Analysis ◽  
High Level ◽  
Additional Nucleotide ◽  
Level Resistance

ABSTRACT Antimicrobial susceptibility testing revealed among 150 clinical isolates of Streptococcus pneumoniae 4 pneumococcal isolates with resistance to fluoroquinolones (MIC of ciprofloxacin, ≥32 μg/ml; MIC of sparfloxacin, ≥16 μg/ml). Gene amplification and sequencing analysis of gyrA andparC revealed nucleotide changes leading to amino acid substitutions in both GyrA and ParC of all four fluoroquinolone-resistant isolates. In the case of strains 182 and 674 for which sparfloxacin MICs were 16 and 64 μg/ml, respectively, nucleotide changes were detected at codon 81 in gyrA and codon 79 in parC; these changes led to an Ser→Phe substitution in GyrA and an Ser→Phe substitution in ParC. Strains 354 and 252, for which sparfloxacin MICs were 128 μg/ml, revealed multiple mutations in both gyrA and parC. These strains exhibited nucleotide changes at codon 85 leading to a Glu→Lys substitution in GyrA, in addition to Ser-79→Tyr and Lys-137→Asn substitutions in ParC. Moreover, strain 252 showed additional nucleotide changes at codon 93, which led to a Trp→Arg substitution in GyrA. These results suggest that sparfloxacin resistance could be due to the multiple mutations in GyrA and ParC. However, it is possible that other yet unidentified mutations may also be involved in the high-level resistance to fluoroquinolones in S. pneumoniae.

scholarly journals Visualizing Amino Acid Substitutions in a Physicochemical Vector Space

2021 ◽  
Author(s):  
Louis R Nemzer
Keyword(s):  
Amino Acid ◽  
Genetic Code ◽  
Three Dimensional ◽  
Point Mutations ◽  
Amino Acid Substitutions ◽  
Standard Genetic Code ◽  
Single Nucleotide ◽  
Single Nucleotide Mutation ◽  
Nucleotide Mutation ◽  
Hereditary Disorders

A three-dimensional representation of the twenty proteinogenic amino acids in a physicochemical space is presented. Vectors corresponding to amino acid substitutions are classified based on whether they are accessible via a single-nucleotide mutation. It is shown that the standard genetic code establishes a "choice architecture" that permits nearly independent tuning of the properties related with size and those related with hydrophobicity. This work sheds light on the metarules of evolvability that may have shaped the standard genetic code to increase the probability that adaptive point mutations will be generated. An illustration of the usefulness of visualizing amino acid substitutions in a 3D physicochemical space is shown using data collected from the SARS-CoV-2 receptor binding domain. The substitutions most responsible for antibody escape are almost always inaccessible via single nucleotide mutation, and also change multiple properties concurrently. The results of this research can extend our understanding of certain hereditary disorders caused by point mutations, as well as guide the development of rational protein and vaccine design.

scholarly journals Pyrosequencing Using the Single-Nucleotide Polymorphism Protocol for Rapid Determination of TEM- and SHV-Type Extended-Spectrum β-Lactamases in Clinical Isolates and Identification of the Novel β-Lactamase Genes blaSHV-48, blaSHV-105, and blaTEM-155

2008 ◽  
Vol 53 (3) ◽  
pp. 977-986 ◽  
Author(s):  
C. Hal Jones ◽  
Alexey Ruzin ◽  
Margareta Tuckman ◽  
Melissa A. Visalli ◽  
Peter J. Petersen ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Amino Acid ◽  
Sequence Data ◽  
Rapid Determination ◽  
The United States ◽  
Amino Acid Substitutions ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extended Spectrum ◽  
Rapid Sequence

ABSTRACT TEM- and SHV-type extended-spectrum β-lactamases (ESBLs) are the most common ESBLs found in the United States and are prevalent throughout the world. Amino acid substitutions at a number of positions in TEM-1 lead to the ESBL phenotype, although substitutions at residues 104 (E to K), 164 (R to S or H), 238 (G to S), and 240 (E to K) appear to be particularly important in modifying the spectrum of activity of the enzyme. The SHV-1-derived ESBLs are a less diverse collection of enzymes; however, the majority of amino acid substitutions resulting in an ESBL mirror those seen in the TEM-1-derived enzymes. Pyrosequencing by use of the single-nucleotide polymorphism (SNP) protocol was applied to provide sequence data at positions critical for the ESBL phenotype spanning the bla TEM and bla SHV genes. Three novel β-lactamases are described: the ESBLs TEM-155 (Q39K, R164S, E240K) and SHV-105 (I8F, R43S, G156D, G238S, E240K) and a non-ESBL, SHV-48 (V119I). The ceftazidime, ceftriaxone, and aztreonam MICs for an Escherichia coli isolate expressing bla SHV-105 were >128, 128, and >128 μg/ml, respectively. Likewise, the ceftazidime, ceftriaxone, and aztreonam MICs for an E. coli isolate expressing bla TEM-155 were >128, 64, and > 128 μg/ml, respectively. Pyrosequence analysis determined the true identity of the β-lactamase on plasmid R1010 to be SHV-11 rather than SHV-1, as previously reported. Pyrosequencing is a real-time sequencing-by-synthesis approach that was applied to SNP detection for TEM- and SHV-type ESBL identification and represents a robust tool for rapid sequence determination that may have a place in the clinical setting.

Single Nucleotide Polymorphisms Influence the Phenotype of Mutations P618A and R1336W found in the ADAMTS13 Gene of Congenital TTP Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2977-2977
Author(s):  
Barbara Plaimauer ◽  
Gabriele Mohr ◽  
Waltraud Wernhart ◽  
Katharina Bruno ◽  
Gerhard Antoine ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Single Amino Acid ◽  
Paternal Allele ◽  
Amino Acid Substitutions ◽  
Common Snps ◽  
Nucleotide Polymorphisms ◽  
Adamts13 Activity ◽  
Maternal Allele ◽  
Single Nucleotide

Abstract ADAMTS13 cleaves plasmatic von Willebrand factor (VWF) between Tyr1605 and Met1606 and regulates thereby the hemostatic activity of VWF. Mutations in the ADAMTS13 gene leading to severe ADAMTS13 deficiency have been found in patients with congenital thrombotic thrombocytopenic purpura (TTP). We have analyzed the ADAMTS13 gene defects in two brothers with hereditary TTP [Antoine et al, Brit. J. Hematol., 2003] where we detected a total of six nucleotide exchanges causing point mutations. On the maternal allele we found an accumulation of five amino acid substitutions (R7W, Q448E, P618A, A732V, R1336W) and on the paternal allele a stop mutation (Q44X) leading to premature protein termination in the propeptide region. Both brothers were double heterozygotes with < 3% of ADAMTS13 activity, whereas their asymptomatic parents have ~ 50% activity. Four (R7W, Q448E, P618A, A732V) of the five maternal mutations constitute single nucleotide polymorphisms (SNP) but R1336W was identified as novel rare mutation in the second cub domain. To evaluate the biologic phenotype of a given haplotype, e.g. the functional significance of the presence of the various SNPs, we analyzed the functional impact of the individual mutations on ADAMTS13 antigen levels and ADAMTS13 activity. A series of mutant ADAMTS13 molecules was expressed which contained either single amino acid substitutions or combinations of mutations with each other. We found that the common SNPs R7W, Q448E and A732V, as single mutations, had either no or only a minor impact on ADAMTS13 secretion and ADAMTS13 activity, whereas P618A and R1336W conferred a dominant adverse effect on ADAMTS13 secretion levels. Co-expression of SNPs R7W or Q448E with SNP P618A lead to improved ADAMTS13 secretion levels and could therefore partly attenuate the detrimental effect of P618A. Concomitant expression of all four SNPs reconstituted secretion levels similar to wild-type implicating a complex synergistically interaction of SNPs located in different ADAMTS13 domain regions, however, functional activity was impaired to 50%. Mutation R1336W was shown to be, as a single amino acid exchange, responsible for reduced ADAMTS13 antigen levels, but in contrast to P618A, the negative effect of R1336W was rather enhanced by the co-expression of R7W and Q448E, than rescued, leading to the total absence of ADAMTS13 secretion from the maternal allele. Our findings provide for the first time evidence that fairly common SNPs, dependent on the presence or absence of other mutations, may differently modulate functional ADAMTS13 protease levels.

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