scholarly journals Molecular evolution of the meningococcal fragments of 7 house-keeping genes

2020 ◽  
Vol 17 (3) ◽  
pp. 301-319
Author(s):  
H. N. Kharkhal ◽  
L. P. Titov ◽  
O. O. Yanovich
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Adenylate Cyclase ◽  
Pyruvate Dehydrogenase ◽  
Amino Acid Substitutions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Aroe Gene ◽  
Average Lead ◽  
Glucose 6 Phosphate Dehydrogenase

The objective of the article was to determine the variability of meningococcal house-keeping gene alleles circulating in Belarus. House-keeping genes sequencing was made by Sanger (ABI 3500). The phylogenetic analysis was done in MEGA X. SNPs were analyzed at pubMLST.org. 60 Belarusian meningococci, collected during 8 years, contain 17 alleles of abcZ gene (5.9 % first identified in Belarus – abcZ 1016) encoding 5 variants of the ABC transporter; 16 adk gene alleles – 2 variants of adenylate cyclase; 17 alleles of aroE gene (11.8 % Belarusian – aroE 944 and aroE 972) – 14 variants of shikimat dehydrogenase; 24 alleles of fumC gene (4.2 % Belarusian – fumC 988) – 4 variants of fumarate dehydratase; 18 alleles of gdh gene (16.7 % first identified in Belarus – gdh 560, gdh 985 and gdh 1083) – 4 variants of glucose-6-phosphate dehydrogenase; 18 alleles of pdhC gene – 11 variants of pyruvate dehydrogenase subunit and 20 alleles of pgm gene – 13 variants of phosphoglucomutase (5.6 and 5 % of Belarusian alleles − pdhC 888 and pgm 1099 respectively). Dominant alleles are abcZ 8 – 25 %, adk 5 – 30, aroE 6 – 28.3, fumC 17 – 30, gdh 560 – 20, pdhC 18 – 21.7, pgm 2 – 25 %. The Belarusian meningococcal population is diverse and includes both its own house-keeping gene alleles (7.7 %) and those circulating in other countries (92.3 %). The number of SNPs is varied from 29 (adk) to 125 (aroE). Single nucleotide polymorphisms are mostly synonymous and, on average, lead to amino acid substitutions in the range from 0.6 % in adenylate cyclase and up to 26.4 % in shikimat dehydrogenase.

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.

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.

In-silico study to identify the pathogenic single nucleotide polymorphisms in the coding region of CDKN2A gene

2021 ◽  
Author(s):  
Farzaneh Ghasemi ◽  
Mehri Khatami ◽  
Mohammad Mehdi Heidari ◽  
Reyhane Chamani
Keyword(s):  
Amino Acid ◽  
High Risk ◽  
Tumor Suppressor ◽  
Single Nucleotide Polymorphisms ◽  
Amino Acid Substitutions ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cdkn2a Gene ◽  
Missense Variants ◽  
Bioinformatics Tools

Background: CDKN2A, encoding two important tumor suppressor proteins p16 and p14, is a tumor suppressor gene. Mutations in this gene and subsequently the defect in p16 and p14 proteins lead to the downregulation of RB1/p53 and cancer malignancy. To identify the structural and functional effects of mutations, various powerful bioinformatics tools are available. The aim of this study is the identification of high-risk non-synonymous single nucleotide variants in the CDKN2A gene via bioinformatics tools. Materials and Methods: Among the identified polymorphisms in this gene, 353 missense variants are retrieved from the national center for biotechnology information/single nucleotide polymorphism database (NCBI/dbSNP). Then, the pathogenicity of missense variants are considered using different bioinformatics tools. The stability of these mutant proteins, conservation of amino acids and the secondary and tertiary structural changes are analyzed by bioinformatics tools. After the identification of high-risk mutations, the changes in the hydrophobicity of high-risk amino acid substitutions are considered. Results: Deleterious single nucleotide polymorphisms (SNPs) were screened step by step using the bioinformatics tools. The results obtained from the set of bioinformatics tools identify high-risk mutations in CDKN2A gene. Conclusion: 18 high-risk mutations including L16R/Q, G23D/R/S, L32P, N42K, G55D, G67D/R, P81R, H83R, G89D/S, A102E, G101R, G122R, and V126D were identified. According to the previous experimental studies, the association of L16R, G23D/R/S, L32P, G67R, H83R, G89D, G101R, and V126D amino acid substitutions with various cancers has been confirmed.

scholarly journals Mechanism of Metronidazole Resistance inHelicobacter pylori: Comparison of the rdxA Gene Sequences in 30 Strains

2000 ◽  
Vol 44 (8) ◽  
pp. 2207-2210 ◽  
Author(s):  
Nadia Maggi Solcà ◽  
Marco Valerio Bernasconi ◽  
Jean-Claude Piffaretti
Keyword(s):  
Phylogenetic Analysis ◽  
Helicobacter Pylori ◽  
Amino Acid ◽  
Resistant Strain ◽  
Point Mutations ◽  
Housekeeping Genes ◽  
Amino Acid Substitutions ◽  
Metronidazole Resistance ◽  
Nucleotide Mutation ◽  
Nucleotide Insertion

ABSTRACT The rdxA gene of 30 independently isolatedHelicobacter pylori strains was sequenced. A comparison of the rdxA sequences revealed a higher percentage of amino acid substitutions in the corresponding protein than in other housekeeping genes. Out of 122 point mutations, 41 were missense and 4 were nonsense. A resistant strain with a nucleotide insertion in therdxA sequence was also found. With the exception of the point mutations and the insertion generating a stop signal, no particular nucleotide mutation or amino acid substitution could be associated to metronidazole resistance. Moreover, phylogenetic analysis of the 30 nucleotide sequences did not demonstrate specific clusters associated with the resistance phenotype.

scholarly journals Molecular epidemiologic characteristics of hemagglutinin from five waves of avian influenza A (H7N9) virus infection, from 2013 to 2017, in Zhejiang Province, China

2021 ◽  
Author(s):  
Yi Sun ◽  
Haiyan Mao ◽  
Xiuyu Lou ◽  
Xinying Wang ◽  
Yin Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Zhejiang Province ◽  
Personal Genome ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Amino Acid Mutations ◽  
Influenza Outbreaks ◽  
Epidemiological Characteristics ◽  
The Waves

AbstractThere have been five waves of influenza A (H7N9) epidemics in Zhejiang Province between 2013 and 2017. Although the epidemiological characteristics of the five waves have been reported, the molecular genetics aspects, including the phylogeny, evolution, and mutation of hemagglutinin (HA), have not been systematically investigated. A total of 154 H7N9 samples from Zhejiang Province were collected between 2013 and 2017 and sequenced using an Ion Torrent Personal Genome Machine. The starting dates of the waves were 16 March 2013, 1 July 2013, 1 July 2014, 1 July 2015, and 1 July 2016. Single-nucleotide polymorphisms (SNPs) and amino acid mutations were counted after the HA sequences were aligned. The evolution of H7N9 matched the temporal order of the five waves, among which wave 3 played an important role. The 55 SNPs and 14 amino acid mutations with high frequency identified among the five waves revealed the dynamic occurrence of mutation in the process of viral dissemination. Wave 3 contributed greatly to the subsequent epidemic of waves 4 and 5 of H7N9. Compared with wave 1, wave 5 was characterized by more mutations, including A143V and R148K, two mutations that have been reported to weaken the immune response. In addition, some amino acid mutations were observed in wave 5 that led to more lineages. It is necessary to strengthen the surveillance of subsequent H7N9 influenza outbreaks.

Phylogeny and Polymorphism in the Long Control Region, E6, and L1 of Human Papillomavirus Types 53, 56, and 66 in Central Brazil

2011 ◽  
Vol 21 (2) ◽  
pp. 222-229 ◽  
Author(s):  
Patrícia Soares Wyant ◽  
Daniela Marreco Cerqueira ◽  
Daniella Sousa Moraes ◽  
José Paulo Gagliardi Leite ◽  
Cláudia Renata Fernandes Martins ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Genetic Variability ◽  
Binding Sites ◽  
Long Control Region ◽  
Amino Acid Substitutions ◽  
Nucleotide Substitutions ◽  
Central Brazil ◽  
Hpv Types ◽  
Genomic Regions

Introduction:Several studies related that different human papillomavirus (HPV) types and intratype variants can present different oncogenic potential. In opposite to HPVs 16 and 18 variants, information about variants of other carcinogenic HPV types is still scarce. The aim of this study was to investigate the genetic variability of HPVs 53, 56, and 66 from Central Brazil isolates.Methods:The long control region (LCR), E6, and L1 genomic regions were amplified and sequenced. We evaluate for nucleotide variations in relation to the reference sequence of each HPV type and also the conservation of physicochemical properties of the deduced amino acid substitutions. In silico analysis was performed to locate binding sites for transcriptional factors within the LCR. Moreover, we performed a phylogenetic analysis with the Central Brazilian and worldwide sequences available at genomic databases.Results:Gathering LCR, E6, and L1 genomic regions, the highest genetic variability was found among HPV-53 isolates with 52 nucleotide variations, followed by HPVs 56 and 66 with 24 and 16 nucleotide substitutions, respectively. The genetic analysis revealed 11 new molecular variants of all HPV types analyzed, totalizing 31 new nucleotide and 3 new amino acid variations. Eight nonconservative amino acid substitutions were detected, which may indicate a biological and pathogenic diversity among HPV types. Furthermore, 8 nucleotide substitutions were localized at putative binding sites for transcription factors in the LCR with a potential implication on viral oncogene expression. The HPVs 53, 56, and 66 phylogenetic analysis confirmed a dichotomic division only described to HPV subtypes and different from the patterns described for HPVs 16 and 18 variants.Conclusions:The high genetic variability observed emphasizes the importance of investigating polymorphisms in types other than HPVs 16 or 18 to better understand the molecular genomic profile of viral infection by different HPV types.

scholarly journals SINGLE-NUCLEOTIDE POLYMORPHISMS OF CALCIUM-SENSING RECEPTOR ENCODING GENE ASSOCIATED WITH CALCIUM KIDNEY STONE DISEASE IN BABYLON PROVINCE

2018 ◽  
Vol 11 (2) ◽  
pp. 417 ◽  
Author(s):  
Zahraa Isam ◽  
Rabab Omran ◽  
Ammad Hassan Mahmood
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Kidney Stone ◽  
Stone Disease ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Calcium Sensing Receptor ◽  
Single Nucleotide ◽  
Kidney Stone Disease ◽  
Calcium Sensing

  Objective: The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that is mainly expressed in the parathyroid and the kidneys where it regulates parathyroid hormone secretion and renal tubular calcium reabsorption. Inactivating and activating CASR gene due to mutations severally caused hypercalcemia or hypocalcemia disorders. The aim of the study was to investigate the risk factor of CASR rs1801725 (Ala986Ser) patients with renal disease.Method: The blood samples were collected from 100 patients and divided into two groups, each one containing 50 samples; chronic kidney disease and end-stage renal disease, who admitted Merjan Teaching Hospital in Babylon Province, Iraq, from February to July 2016. In addition, healthy persons as a control group (50 samples). Genotyping of CASR single-nucleotide polymorphisms (SNP) was performed using a polymerase chain reaction technique, followed by single-strand conformation polymorphism. Accordingly, these DNA polymorphisms were confirmed using DNA sequencing.Results: The conformational haplotypes of CASR, exon7 NCBI Primer3plus reference were obtained in three patterns, including two, three, and four bands, due to the presence SNPs within the studied region. These SNPs leads to change three amino acid residues of CASR, including amino acid substitutions were Ala 128→ Ser 128, Leu 155→Tye 155, and Leu 156→ Ser 156 that may affect or modified the tertiary structure of the receptor, subsequently the function like the affinity to calcium ion may be effected.Conclusion: These results suggest that the variants of CASR SNP, namely, rs1801725 might be involved in susceptibility to kidney stone disease.

scholarly journals Spontaneous Mutations in thePlasmodium falciparumSarcoplasmic/ Endoplasmic Reticulum Ca2+-ATPase (PfATP6) Gene among Geographically Widespread Parasite Populations Unexposed to Artemisinin-Based Combination Therapies

2010 ◽  
Vol 55 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Kazuyuki Tanabe ◽  
Sedigheh Zakeri ◽  
Nirianne Marie Q. Palacpac ◽  
Manada Afsharpad ◽  
Milijaona Randrianarivelojosia ◽  
...  
Keyword(s):  
Amino Acid ◽  
South America ◽  
Artemisinin Resistance ◽  
Common Snps ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Single Nucleotide ◽  
Baseline Information ◽  
A Minor ◽  
Parasite Populations

ABSTRACTRecent reports on the decline of the efficacy of artemisinin-based combination therapies (ACTs) indicate a serious threat to malaria control. The endoplasmic/sarcoplasmic reticulum Ca2+-ATPase ortholog ofPlasmodium falciparum(PfSERCA) has been suggested to be the target of artemisinin and its derivatives. It is assumed that continuous artemisinin pressure will affect polymorphism of the PfSERCA gene (serca) if the protein is the target. Here, we investigated the polymorphism ofsercain parasite populations unexposed to ACTs to obtain baseline information for the study of potential artemisinin-driven selection of resistant parasites. Analysis of 656 full-length sequences from 13 parasite populations in Africa, Asia, Oceania, and South America revealed 64 single nucleotide polymorphisms (SNPs), of which 43 were newly identified and 38 resulted in amino acid substitutions. No isolates showed L263E and S769N substitutions, which were reportedly associated with artemisinin resistance. Among the four continents, the number of SNPs was highest in Africa. In Africa, Asia, and Oceania, common SNPs, or those with a minor allele frequency of ≥0.05, were less prevalent, with most SNPs noted to be continent specific, whereas in South America, common SNPs were highly prevalent and often shared with those in Africa. Of 50 amino acid haplotypes observed, only one haplotype (3D7 sequence) was seen in all four continents (64%). Forty-eight haplotypes had frequencies of less than 5%, and 40 haplotypes were continent specific. The geographical difference in the diversity and distribution ofsercaSNPs and haplotypes lays the groundwork for assessing whether some artemisinin resistance-associated mutations and haplotypes are selected by ACTs.

scholarly journals The complete chloroplast genome of Limonium tetragonum (Plumbaginaceae) isolated in Korea

2021 ◽  
Vol 51 (3) ◽  
pp. 337-344
Author(s):  
Yongsung KIM ◽  
Hong XI ◽  
Jongsun PARK
Keyword(s):  
Phylogenetic Analysis ◽  
Chloroplast Genome ◽  
Phylogenetic Trees ◽  
Sister Group ◽  
Single Copy ◽  
Nucleotide Polymorphisms ◽  
Large Single Copy ◽  
Single Nucleotide ◽  
Complete Chloroplast Genome ◽  
Cp Genome

The chloroplast genome of Limonium tetragonum (Thunb.) Bullock, a halophytic species, was sequenced to understand genetic differences based on its geographical distribution. The cp genome of L. tetragonum was 154,689 bp long (GC ratio is 37.0%) and has four subregions: 84,572 bp of large single-copy (35.3%) and 12,813 bp of small singlecopy (31.5%) regions were separated by 28,562 bp of inverted repeat (40.9%) regions. It contained 128 genes (83 proteincoding genes, eight rRNAs, and 37 tRNAs). Thirty-five single-nucleotide polymorphisms and 33 INDEL regions (88 bp in length) were identified. Maximum-likelihood and Bayesian inference phylogenetic trees showed that L. tetragonum formed a sister group with L. aureum, which is incongruent with certain previous studies, including a phylogenetic analysis.

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