Development of an automation system for single nucleotide polymorphisms genotyping using bio-strand, a new three-dimensional microarray

2005 ◽  
Vol 99 (2) ◽  
pp. 120-124 ◽  
Author(s):  
Yuriko Tojo ◽  
Junko Asahina ◽  
Yukiko Miyashita ◽  
Masaaki Takahashi ◽  
Naoko Matsumoto ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Three Dimensional ◽  
Automation System ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

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.

A survey of proteins encoded by non-synonymous single nucleotide polymorphisms reveals a significant fraction with altered stability and activity

2009 ◽  
Vol 424 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Abdellah Allali-Hassani ◽  
Gregory A. Wasney ◽  
Irene Chau ◽  
Bum Soo Hong ◽  
Guillermo Senisterra ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Three Dimensional ◽  
Catalytic Efficiency ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Coding Region ◽  
Wild Type Enzyme ◽  
Single Nucleotide ◽  
The Stability ◽  
And Function

On average, each human gene has approximately four SNPs (single nucleotide polymorphisms) in the coding region, half of which are nsSNPs (non-synonymous SNPs) or missense SNPs. Current attention is focused on those that are known to perturb function and are strongly linked to disease. However, the vast majority of SNPs have not been investigated for the possibility of causing disease. We set out to assess the fraction of nsSNPs that encode proteins that have altered stability and activity, for this class of variants would be candidates to perturb cellular function. We tested the thermostability and, where possible, the catalytic activity for the most common variant (wild-type) and minor variants (total of 46 SNPs) for 16 human enzymes for which the three-dimensional structures were known. There were significant differences in the stability of almost half of the variants (48%) compared with their wild-type counterparts. The catalytic efficiency of approx. 14 variants was significantly altered, including several variants of human PKM2 (pyruvate kinase muscle 2). Two PKM2 variants, S437Y and E28K, also exhibited changes in their allosteric regulation compared with the wild-type enzyme. The high proportion of nsSNPs that affect protein stability and function, albeit subtly, underscores the need for experimental analysis of the diverse human proteome.

scholarly journals Computational and Mass Spectrometry-Based Approach Identify Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) in JMJD6

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4653
Author(s):  
Tianqi Gong ◽  
Lujie Yang ◽  
Fenglin Shen ◽  
Hao Chen ◽  
Ziyue Pan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Progression ◽  
Three Dimensional ◽  
Prediction Method ◽  
Mrna Splicing ◽  
Dimensional Structure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Liquid Chromatography Tandem Mass

The jumonji domain-containing protein 6 (JMJD6) gene catalyzes the arginine demethylation and lysine hydroxylation of histone and a growing list of its known substrate molecules, including p53 and U2AF65, suggesting a possible role in mRNA splicing and transcription in cancer progression. Mass spectrometry-based technology offers the opportunity to detect SNP variants accurately and effectively. In our study, we conducted a combined computational and filtration workflow to predict the nonsynonymous single nucleotide polymorphisms (nsSNPs) present in JMJD6, followed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and validation. The computational approaches SIFT, PolyPhen-2, SNAP, I-Mutant 2.0, PhD-SNP, PANTHER, and SNPS&GO were integrated to screen out the predicted damaging/deleterious nsSNPs. Through the three-dimensional structure of JMJD6, H187R (rs1159480887) was selected as a candidate for validation. The validation experiments showed that the mutation of this nsSNP in JMJD6 obviously affected mRNA splicing or the transcription of downstream genes through the reduced lysyl-hydroxylase activity of its substrates, U2AF65 and p53, further indicating the accuracy of this prediction method. This research provides an effective computational workflow for researchers with an opportunity to select prominent deleterious nsSNPs and, thus, remains promising for examining the dysfunction of proteins.

Development of a simple method for the determination of single nucleotide polymorphisms

2010 ◽  
Vol 34 (8) ◽  
pp. S75-S75
Author(s):  
Weifeng Zhu ◽  
Zhuoqi Liu ◽  
Daya Luo ◽  
Xinyao Wu ◽  
Fusheng Wan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Simple Method ◽  
Single Nucleotide
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