Three single nucleotide polymorphisms leading to non-synonymous amino acid substitution in the human ribonuclease 2 and angiogenin genes exhibit markedly less genetic heterogeneity in six populations

2008 ◽  
Vol 26 (6) ◽  
pp. 718-722 ◽  
Author(s):  
Misuzu Ueki ◽  
Haruo Takeshita ◽  
Junko Fujihara ◽  
Hisakazu Takatsuka ◽  
Isao Yuasa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Amino Acid Substitution ◽  
Genetic Heterogeneity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Predicting Amino Acid Substitution Probabilities Using Single Nucleotide Polymorphisms

Genetics ◽  
2017 ◽  
pp. genetics.300078.2017
Author(s):  
Francesca Rizzato ◽  
Alex Rodriguez ◽  
Xevi Biarnés ◽  
Alessandro Laio
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Amino Acid Substitution ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

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.

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 Identification of Amino Acid Substitutions with Compensational Effects in the Attachment Protein of Canine Distemper Virus

2014 ◽  
Vol 88 (14) ◽  
pp. 8057-8064 ◽  
Author(s):  
Ursula Sattler ◽  
Mojtaba Khosravi ◽  
Mislay Avila ◽  
Paola Pilo ◽  
Johannes P. Langedijk ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Canine Distemper Virus ◽  
Nucleotide Polymorphisms ◽  
Canine Distemper ◽  
Wild Type ◽  
Attachment Protein ◽  
Single Nucleotide ◽  
Hemagglutinin Gene ◽  
H Gene

ABSTRACTThe hemagglutinin (H) gene of canine distemper virus (CDV) encodes the receptor-binding protein. This protein, together with the fusion (F) protein, is pivotal for infectivity since it contributes to the fusion of the viral envelope with the host cell membrane. Of the two receptors currently known for CDV (nectin-4 and the signaling lymphocyte activation molecule [SLAM]), SLAM is considered the most relevant for host susceptibility. To investigate how evolution might have impacted the host-CDV interaction, we examined the functional properties of a series of missense single nucleotide polymorphisms (SNPs) naturally accumulating within the H-gene sequences during the transition between two distinct but related strains. The two strains, a wild-type strain and a consensus strain, were part of a single continental outbreak in European wildlife and occurred in distinct geographical areas 2 years apart. The deduced amino acid sequence of the two H genes differed at 5 residues. A panel of mutants carrying all the combinations of the SNPs was obtained by site-directed mutagenesis. The selected mutant, wild type, and consensus H proteins were functionally evaluated according to their surface expression, SLAM binding, fusion protein interaction, and cell fusion efficiencies. The results highlight that the most detrimental functional effects are associated with specific sets of SNPs. Strikingly, an efficient compensational system driven by additional SNPs appears to come into play, virtually neutralizing the negative functional effects. This system seems to contribute to the maintenance of the tightly regulated function of the H-gene-encoded attachment protein.IMPORTANCETo investigate how evolution might have impacted the host-canine distemper virus (CDV) interaction, we examined the functional properties of naturally occurring single nucleotide polymorphisms (SNPs) in the hemagglutinin gene of two related but distinct strains of CDV. The hemagglutinin gene encodes the attachment protein, which is pivotal for infection. Our results show that few SNPs have a relevant detrimental impact and they generally appear in specific combinations (molecular signatures). These drastic negative changes are neutralized by compensatory mutations, which contribute to maintenance of an overall constant bioactivity of the attachment protein. This compensational mechanism might reflect the reaction of the CDV machinery to the changes occurring in the virus following antigenic variations critical for virulence.

scholarly journals (6) Highly Polymorphic Genesin Cultivated Tomato

HortScience ◽  
2005 ◽  
Vol 40 (4) ◽  
pp. 999A-999
Author(s):  
Angela Baldo ◽  
Larry Robertson ◽  
Joanne Labate
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Germplasm Conservation ◽  
Wild Relatives ◽  
Nonsynonymous Snps ◽  
Nucleotide Polymorphisms ◽  
Nucleotide Polymorphism ◽  
Tomato Genome ◽  
Single Nucleotide

Cultivated tomato varieties are genetically extremely similar. We identified 764 Unigenes with potential single nucleotide polymorphisms (SNPs) among more than 15 cultivars from public expressed tomato data. By sequencing regions from 53 of these Unigenes in two to three cultivars, we discovered an unexpected wealth of nucleotide polymorphism (62 SNPs and 12 indels in 21 Unigenes). This included a high proportion of predicted nonsynonymous nucleotide (17 of 33 SNPs in exons) and nonconservative amino acid (6 of 16 nonsynonymous SNPs) changes. We hypothesize that five of these regions are associated with introgressions from wild relatives. Identifying polymorphic, expressed genes in the tomato genome will be useful for both tomato improvement and germplasm conservation.

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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