scholarly journals Multicapillary Electrophoresis Analysis of Single-Nucleotide Sequence Variations in the Deoxycytidine Kinase Gene

2006 ◽  
Vol 52 (9) ◽  
pp. 1756-1762 ◽  
Author(s):  
Eszter Szantai ◽  
Zsolt Ronai ◽  
Maria Sasvari-Szekely ◽  
Günther Bonn ◽  
András Guttman
Keyword(s):  
Nucleotide Sequence ◽  
Complex Traits ◽  
Large Scale ◽  
Deoxycytidine Kinase ◽  
Individual Response ◽  
Kinase Gene ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Sequence Variations ◽  
The Individual

Abstract Background: Investigation of the genetic background of complex traits is the focus of recent interest, as several common diseases or the individual response to treatments of various illnesses have not yet been explored. These studies require the development and implementation of reliable and large-scale genotyping methods. In this report, we introduce an efficient technique based on PCR–restriction fragment length sequence variation technique for the analysis of the −360CG and −201CT single-nucleotide sequence variations in the deoxycytidine kinase gene. Methods: A multicapillary gel electrophoresis instrument was used for the size determination of the generated DNA fragments. A healthy Hungarian population of 100 individuals was investigated to determine allele and genotype frequencies for the 2 sequence variations of interest. Results: We found that the occurrence of the minor allele is rather low, i.e., the frequency of both the −360G and −201T variants is 1%. Conclusions: Our technique can readily facilitate the analysis of these important sequence variations in other ethnic groups to clarify the role of these sequence variations in conjunction with arabinosylcytosine treatment in acute myeloid leukemia.

Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 118-125 ◽  
Author(s):  
Barbara Plaimauer ◽  
Jakob Fuhrmann ◽  
Gabriele Mohr ◽  
Waltraud Wernhart ◽  
Katharina Bruno ◽  
...  
Keyword(s):  
Amino Acid ◽  
Missense Mutation ◽  
Specific Activity ◽  
Phenotypic Expression ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Common Amino Acid ◽  
Sequence Variations ◽  
Adamts13 Deficiency ◽  
The Individual

Abstract Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases.

scholarly journals Short-term modulation of the lesioned language network

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Gesa Hartwigsen ◽  
Anika Stockert ◽  
Louise Charpentier ◽  
Max Wawrzyniak ◽  
Julian Klingbeil ◽  
...  
Keyword(s):  
Large Scale ◽  
Right Hemisphere ◽  
Functional Neuroimaging ◽  
Inferior Frontal Gyrus ◽  
Individual Response ◽  
Short Term ◽  
Large Scale Networks ◽  
The Individual ◽  
The Right ◽  
Language Network

Language is sustained by large-scale networks in the human brain. Stroke often severely affects function and network dynamics. However, the adaptive potential of the brain to compensate for lesions is poorly understood. A key question is whether upregulation of the right hemisphere is adaptive for language recovery. Targeting the potential for short-term reorganization in the lesioned brain, we applied 'virtual lesions' over left anterior or posterior inferior frontal gyrus (IFG) in post-stroke patients with left temporo-parietal lesions prior to functional neuroimaging. Perturbation of the posterior IFG selectively delayed phonological decisions and decreased phonological activity. The individual response delay was correlated with the upregulation of the lesion homologue, likely reflecting compensation. Moreover, stronger individual tract integrity of the right superior longitudinal fascicle was associated with lesser disruption. Our results provide evidence for functional and structural underpinnings of plasticity in the lesioned language network, and a compensatory role of the right hemisphere.

Models, Practices and Methods of Reading: Evolution in Time and Space

2009 ◽  
pp. 59-64
Author(s):  
Yulia P. Melentyeva
Keyword(s):  
Large Scale ◽  
Social Groups ◽  
National Program ◽  
Time And Space ◽  
Lack Of Information ◽  
The Individual

In recent years as public in general and specialist have been showing big interest to the matters of reading. According to discussion and launch of the “Support and Development of Reading National Program”, many Russian libraries are organizing the large-scale events like marathons, lecture cycles, bibliographic trainings etc. which should draw attention of different social groups to reading. The individual forms of attraction to reading are used much rare. To author’s mind the main reason of such an issue has to be the lack of information about forms and methods of attraction to reading.

scholarly journals The Evolution of Isochores: Evidence From SNP Frequency Distributions

Genetics ◽  
2002 ◽  
Vol 162 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Martin J Lercher ◽  
Nick G C Smith ◽  
Adam Eyre-Walker ◽  
Laurence D Hurst
Keyword(s):  
Population Genetics ◽  
Large Scale ◽  
Gc Content ◽  
Nucleotide Composition ◽  
Compositional Variation ◽  
Mutation Bias ◽  
Single Nucleotide ◽  
Frequency Distributions ◽  
Noncoding Regions ◽  
Standard Population

AbstractThe large-scale systematic variation in nucleotide composition along mammalian and avian genomes has been a focus of the debate between neutralist and selectionist views of molecular evolution. Here we test whether the compositional variation is due to mutation bias using two new tests, which do not assume compositional equilibrium. In the first test we assume a standard population genetics model, but in the second we make no assumptions about the underlying population genetics. We apply the tests to single-nucleotide polymorphism data from noncoding regions of the human genome. Both models of neutral mutation bias fit the frequency distributions of SNPs segregating in low- and medium-GC-content regions of the genome adequately, although both suggest compositional nonequilibrium. However, neither model fits the frequency distribution of SNPs from the high-GC-content regions. In contrast, a simple population genetics model that incorporates selection or biased gene conversion cannot be rejected. The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Spectral Pitch Similarity is a Predictor of Perceived Change in Sound- as Well as Note-Based Music

2019 ◽  
Vol 2 ◽  
pp. 205920431984735
Author(s):  
Roger T. Dean ◽  
Andrew J. Milne ◽  
Freya Bailes
Keyword(s):  
Time Series ◽  
Piano Music ◽  
Individual Response ◽  
Discrete Events ◽  
Acoustic Intensity ◽  
Spectral Parameters ◽  
Cross Sectional ◽  
Perceived Change ◽  
Predictive Role ◽  
The Individual

Spectral pitch similarity (SPS) is a measure of the similarity between spectra of any pair of sounds. It has proved powerful in predicting perceived stability and fit of notes and chords in various tonal and microtonal instrumental contexts, that is, with discrete tones whose spectra are harmonic or close to harmonic. Here we assess the possible contribution of SPS to listeners’ continuous perceptions of change in music with fewer discrete events and with noisy or profoundly inharmonic sounds, such as electroacoustic music. Previous studies have shown that time series of perception of change in a range of music can be reasonably represented by time series models, whose predictors comprise autoregression together with series representing acoustic intensity and, usually, the timbral parameter spectral flatness. Here, we study possible roles for SPS in such models of continuous perceptions of change in a range of both instrumental (note-based) and sound-based music (generally containing more noise and fewer discrete events). In the first analysis, perceived change in three pieces of electroacoustic and one of piano music is modeled, to assess the possible contribution of (de-noised) SPS in cooperation with acoustic intensity and spectral flatness series. In the second analysis, a broad range of nine pieces is studied in relation to the wider range of distinctive spectral predictors useful in previous perceptual work, together with intensity and SPS. The second analysis uses cross-sectional (mixed-effects) time series analysis to take advantage of all the individual response series in the dataset, and to assess the possible generality of a predictive role for SPS. SPS proves to be a useful feature, making a predictive contribution distinct from other spectral parameters. Because SPS is a psychoacoustic “bottom up” feature, it may have wide applicability across both the familiar and the unfamiliar in the music to which we are exposed.

scholarly journals Bayesian reassessment of the epigenetic architecture of complex traits

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Trejo Banos ◽  
Daniel L. McCartney ◽  
Marion Patxot ◽  
Lucas Anchieri ◽  
Thomas Battram ◽  
...  
Keyword(s):  
Complex Traits ◽  
Complex Disease ◽  
Target Identification ◽  
Blood Cholesterol ◽  
Methylation Array ◽  
Single Nucleotide ◽  
Epigenetic Effects ◽  
Probability Prediction ◽  
Stimuli Response ◽  
Insight Into

Abstract Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal.

scholarly journals Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Crop Breeding ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Phenotype Identification

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.

LONG‐TIME RESPONSE PREDICTED BY EXACT ELASTIC RAY THEORY

Geophysics ◽  
1965 ◽  
Vol 30 (3) ◽  
pp. 363-368 ◽  
Author(s):  
T. W. Spencer
Keyword(s):  
Formal Solution ◽  
Intermediate Stage ◽  
Time Limit ◽  
Time Interval ◽  
Individual Response ◽  
Axially Symmetric ◽  
Long Time ◽  
The Difference ◽  
The Individual ◽  
Significant Figures

The formal solution for an axially symmetric radiation field in a multilayered, elastic system can be expanded in an infinite series. Each term in the series is associated with a particular raypath. It is shown that in the long‐time limit the individual response functions produced by a step input in particle velocity are given by polynomials in odd powers of the time. For rays which suffer m reflections, the degree of the polynomials is 2m+1. The total response is obtained by summing all rays which contribute in a specified time interval. When the rays are selected indiscriminately, the difference between the magnitude of the partial sum at an intermediate stage of computation and the magnitude of the correct total sum may be greater than the number of significant figures carried by the computer. A prescription is stated for arranging the rays into groups. Each group response function varies linearly in the long‐time limit and goes to zero when convolved with a physically realizable source function.

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