scholarly journals A Comparison of DNA Pools Constructed Following Whole Genome Amplification for Two-Stage SNP Genotyping Designs

2005 ◽  
Vol 8 (4) ◽  
pp. 353-361 ◽  
Author(s):  
Zhen Zhen Zhao ◽  
Dale R. Nyholt ◽  
Michael R. James ◽  
Renee Mayne ◽  
Susan A. Treloar ◽  
...  
Keyword(s):  
Multiple Displacement Amplification ◽  
Cost Effective ◽  
Mean Difference ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Individual Genotyping ◽  
Dna Pools ◽  
Snp Validation ◽  
Using Data ◽  
Time Required

AbstractGenotyping in DNA pools reduces the cost and the time required to complete large genotyping projects. The aim of the present study was to evaluate pooling as part of a strategy for fine mapping in regions of significant linkage. Thirty-nine single nucleotide polymorphisms (SNPs) were analyzed in two genomic DNA pools of 384 individuals each and results compared with data after typing all individuals used in the pools. There were no significant differences using data from either 2 or 8 heterozygous individuals to correct frequency estimates for unequal allelic amplification. After correction, the mean difference between estimates from the genomic pool and individual allele frequencies was .033. A major limitation of the use of DNA pools is the time and effort required to carefully adjust the concentration of each individual DNA sample before mixing aliquots. Pools were also constructed by combining DNA after Multiple Displacement Amplification (MDA). The MDA pools gave similar results to pools constructed after careful DNA quantitation (mean difference from individual genotyping .040) and MDA provides a rapid method to generate pools suitable for some applications. Pools provide a rapid and cost-effective screen to eliminate SNPs that are not polymorphic in a test population and can detect minor allele frequencies as low as 1% in the pooled samples. With current levels of accuracy, pooling is best suited to an initial screen in the SNP validation process that can provide high-throughput comparisons between cases and controls to priori- tize SNPs for subsequent individual genotyping.

Association Between CYP3A4 and CYP3A5 Genotypes and Cyclosporine's Blood Levels and Doses among Jordanian Kidney Transplanted Patients

2019 ◽  
Vol 20 (8) ◽  
pp. 682-694 ◽  
Author(s):  
Sahar El-Shair ◽  
Mohammad Al Shhab ◽  
Khaled Zayed ◽  
Moaath Alsmady ◽  
Malek Zihlif
Keyword(s):  
Kidney Transplantation ◽  
Strong Association ◽  
Mean Difference ◽  
Allele Frequencies ◽  
Assay Method ◽  
Therapeutic Window ◽  
Blood Levels ◽  
Nucleotide Polymorphisms ◽  
Significant Difference ◽  
The Mean

Background: Cyclosporine is used as an immunosuppressive agent in kidney transplantation. It has a narrow therapeutic window. Cyclosporine is predominantly metabolized by CYP3A4 and CYP3A5. The most common Single Nucleotide Polymorphisms (SNPs) affecting cyclosporine metabolism (CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3) were investigated among Jordanian kidney transplanted patients to find out the genotypes and allele frequencies of these SNPs. Additionally, this study investigated whether genotypes of CYP3A4 and CYP3A5 affect C2 blood levels, dosing of cyclosporine and the prevalence of acute rejection. Methods: Blood samples of 109 adult patients taking cyclosporine as their primary immunosuppressant for kidney transplantation were collected from the Prince Hamzah Hospital, Amman, Jordan. Patients’ first C2 blood levels and their first two given doses were collected. Patients were genotyped for the four SNPs using Polymerase Chain Reaction- restriction Fragment Length Polymorphism (PCR-RFLP) assay method. Results: Allele frequencies among Jordanian patients for CYP3A4*1B, CYP3A4*1G, CYP3A4*22 and CYP3A5*3 were 0.037, 0.399, 0.037 and 0.271, respectively. There was a significant association between CYP3A4*22 and mean difference in the second and first given doses (P=0.034). There was a big difference between CYP3A4*22 and the mean of the first C2 blood levels (P=0.063). Conclusion: There was a strong association between CYP3A4*22 and the mean difference between the second and first given doses. There was a trend of significant difference between the mean of the first C2 blood levels among heterozygous CYP3A4*22 patients. Pharmacogenomics may hold promise in assisting the prediction of the best cyclosporine dose and C2 blood level among Jordanian kidney transplant patients.

scholarly journals Assessing Allele Frequencies of Single Nucleotide Polymorphisms in DNA Pools by PyrosequencingTM Technology

BioTechniques ◽  
2002 ◽  
Vol 32 (5) ◽  
pp. 1144-1152 ◽  
Author(s):  
Jon Wasson ◽  
Gary Skolnick ◽  
Latisha Love-Gregory ◽  
M. Alan Permutt
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Pools

scholarly journals Evaluation of a New Pooling Strategy Based on Leukocyte Count for Rapid Quantification of Allele Frequencies

2007 ◽  
Vol 53 (5) ◽  
pp. 980-982 ◽  
Author(s):  
Heidi Rossmann ◽  
Elena Büchler ◽  
Jürgen J Wenzel ◽  
Carolin Neukirch ◽  
Jean-Baptist du Prel ◽  
...  
Keyword(s):  
Whole Blood ◽  
Leukocyte Count ◽  
Allele Frequencies ◽  
Published Data ◽  
Nucleotide Polymorphisms ◽  
Dna Pooling ◽  
Blood Samples ◽  
Dna Concentration ◽  
Dna Pools ◽  
Whole Blood Samples

Abstract Background: Allele frequencies of single-nucleotide polymorphisms (SNPs) can be quantified from DNA pools. The conventional preparation of DNA pools requires DNA isolation and quantification for each blood sample. We hypothesized that pooling of whole blood samples according to their leukocyte count, which determines DNA content, would be as reliable as the conventional pooling method but much less tedious to perform. Methods: We collected 100 whole blood samples and measured the leukocyte count. Samples were frozen until further use. After thawing, pools were generated by combining aliquots containing an equal number of leukocytes. In parallel, DNA was extracted from another aliquot, DNA concentration was measured, and DNA concentration-based pools were assembled. All original samples were genotyped directly using 4 different SNP assays to obtain the exact allele frequencies in the pool. In addition, samples of known genotypes were mixed according to the DNA concentration or the leukocyte count to generate artificial samples of known allele frequencies. We analyzed pools and mixes in triplicate by pyrosequencing and calculated allelic frequencies. Results: Leukocyte and DNA pooling provided equally accurate and precise SNP frequencies comparable to published data. Conclusion: DNA and leukocyte pooling are both suitable strategies to determine allele frequencies in frozen samples. The leukocyte pooling approach is much less tedious, quicker, and less expensive. It should be always considered if leukocyte counts are available.

EpiPen: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

scholarly journals Modeling Fused Filament Fabrication using Artificial Neural Networks

2021 ◽  
Author(s):  
Paul Oehlmann ◽  
Paul Osswald ◽  
Juan Camilo Blanco ◽  
Martin Friedrich ◽  
Dominik Rietzel ◽  
...  
Keyword(s):  
Real Time ◽  
Large Scale ◽  
Cost Effective ◽  
Print Quality ◽  
Ann Model ◽  
Production Environment ◽  
Fused Filament Fabrication ◽  
Artificial Neural ◽  
Using Data ◽  
Artificial Neural Network Ann

AbstractWith industries pushing towards digitalized production, adaption to expectations and increasing requirements for modern applications, has brought additive manufacturing (AM) to the forefront of Industry 4.0. In fact, AM is a main accelerator for digital production with its possibilities in structural design, such as topology optimization, production flexibility, customization, product development, to name a few. Fused Filament Fabrication (FFF) is a widespread and practical tool for rapid prototyping that also demonstrates the importance of AM technologies through its accessibility to the general public by creating cost effective desktop solutions. An increasing integration of systems in an intelligent production environment also enables the generation of large-scale data to be used for process monitoring and process control. Deep learning as a form of artificial intelligence (AI) and more specifically, a method of machine learning (ML) is ideal for handling big data. This study uses a trained artificial neural network (ANN) model as a digital shadow to predict the force within the nozzle of an FFF printer using filament speed and nozzle temperatures as input data. After the ANN model was tested using data from a theoretical model it was implemented to predict the behavior using real-time printer data. For this purpose, an FFF printer was equipped with sensors that collect real time printer data during the printing process. The ANN model reflected the kinematics of melting and flow predicted by models currently available for various speeds of printing. The model allows for a deeper understanding of the influencing process parameters which ultimately results in the determination of the optimum combination of process speed and print quality.

scholarly journals Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rattanaporn Sukprasong ◽  
Sumonrat Chuwongwattana ◽  
Napatrupron Koomdee ◽  
Thawinee Jantararoungtong ◽  
Santirhat Prommas ◽  
...  
Keyword(s):  
Snp Genotyping ◽  
Allele Frequencies ◽  
Nucleotide Polymorphisms ◽  
Poor Metabolizer ◽  
Thai Population ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Genotyping Assay ◽  
Intermediate Metabolizer ◽  
Important Drug

AbstractPrior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.

scholarly journals First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 931
Author(s):  
Chi-Leung Chiang ◽  
Sik-Kwan Chan ◽  
Shing-Fung Lee ◽  
Horace Cheuk-Wai Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cost Effectiveness ◽  
Lifetime Cost ◽  
Cost Effective ◽  
First Line ◽  
First Line Therapy ◽  
Payer Perspective ◽  
Life Years ◽  
Using Data

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

scholarly journals A SNaPshot Assay for Determination of the Mannose-Binding Lectin Gene Variants and an Algorithm for Calculation of Haplogenotype Combinations

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Jana Mrazkova ◽  
Petr Sistek ◽  
Jan Lochman ◽  
Lydie Izakovicova Holla ◽  
Zdenek Danek ◽  
...  
Keyword(s):  
Association Studies ◽  
Genetic Association Studies ◽  
Cost Effective ◽  
European Population ◽  
Mannose Binding Lectin ◽  
Nucleotide Polymorphisms ◽  
Online Application ◽  
Czech Population ◽  
Mannose Binding ◽  
Binding Lectin

Mannose-binding lectin (MBL) deficiency caused by the variability in the MBL2 gene is responsible for the susceptibility to and severity of various infectious and autoimmune diseases. A combination of six single nucleotide polymorphisms (SNPs) has a major impact on MBL levels in circulation. The aim of this study is to design and validate a sensitive and economical method for determining MBL2 haplogenotypes. The SNaPshot assay is designed and optimized to genotype six SNPs (rs1800451, rs1800450, rs5030737, rs7095891, rs7096206, rs11003125) and is validated by comparing results with Sanger sequencing. Additionally, an algorithm for online calculation of haplogenotype combinations from the determined genotypes is developed. Three hundred and twenty-eight DNA samples from healthy individuals from the Czech population are genotyped. Minor allele frequencies (MAFs) in the Czech population are in accordance with those present in the European population. The SNaPshot assay for MBL2 genotyping is a high-throughput, cost-effective technique that can be used in further genetic-association studies or in clinical practice. Moreover, a freely available online application for the calculation of haplogenotypes from SNPs is developed within the scope of this project.

Sign in / Sign up

Export Citation Format

Share Document