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Results for “Single nucleotide polymorphisms (SNPs)”

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At least 271 records · Page 15Linked to original sources
PubMed2004

Mining single nucleotide polymorphisms from EST data of silkworm, Bombyx mori, inbred strain Dazao.

We made use of 81,635 expressed sequence tags (ESTs) derived from 12 different cDNA libraries of the silkworm, Bombyx mori, inbred strain Dazao (P50), to identify high-quality candidate single nucleotide polymorphisms (SNPs). By PHRAP assembling, 12,980 contigs containing 11,537 contigs assembled by more than one read were obtained, and 101 candidate SNPs and 27 single base insertions/deletions were identified from 117 contigs assembled from 1576 high-quality reads base-called with PHRED and screened on the basis of the neighborhood quality standard (NQS). Simultaneously, we also predicted 40 SNPs in coding regions (cSNPs), of which 26 were predicted to lead to amino acid non-synonymous variations and 14 synonymous substitutions. Also, the 1.66:1 ratio of transition/transversion is different from that of other insects. As the first SNP analysis of a Lepidoptera, B. mori, the single nucleotide polymorphic density is estimated to be 1.3 x 10(-3) by sequence diversity. This analysis shows that expressed sequences from multiple libraries may provide an abundant source of comparative reads to mine for cSNPs from the silkworm genome.

Amino Acid Substitution↗
PubMed2004

A FRET-based analysis of SNPs without fluorescent probes.

Fluorescence resonance energy transfer (FRET) is a simple procedure for detecting specific DNA sequences, and is therefore used in many fields. However, the cost is relatively high, because FRET-based methods usually require fluorescent probes. We have designed a cost-effective way of using FRET, and developed a novel approach for the genotyping of single nucleotide polymorphisms (SNPs) and allele frequency estimation. The key feature of this method is that it uses a DNA-binding fluorogenic molecule, SYBR Green I, as an energy donor for FRET. In this method, single base extension is performed with dideoxynucleotides labeled with an orange dye and a red dye in the presence of SYBR Green I. The dyes incorporated into the extended products accept energy from SYBR Green I and emit fluorescence. We have validated the method with ten SNPs, which were successfully discriminated by end-point measurements of orange and red fluorescence intensity in a microplate fluorescence reader. Using a mixture of homozygous samples, we also confirmed the potential of this method for estimation of allele frequency. Application of this strategy to large-scale studies will reduce the time and cost of genotyping a vast number of SNPs.

Benzothiazoles↗
PubMed2002

Novel SNPs in a candidate gene, CRTH2, for allergic diseases.

Sequencing analyses of genomic DNA samples from a Chinese population identified four single-nucleotide polymorphisms (SNPs) of the CRTH2 gene, encoding a chemoattractant receptor predominantly expressed on Th2 cells and a receptor for prostaglandin D2 (PGD2). Two coding-region SNPs with a T to G and a C to A substitutions, resulting in codon changes from Phe to Val and Pro to Thr, respectively. Two additional SNPs were discovered in the 3' untranslated region (3'-UTR). These newly identified SNPs will be useful for further functional study of variant CRTH2 gene, and for genetic studies of asthma and other immunologic diseases.

Base Sequence↗
PubMed2004

Analysis of SNPs in pooled DNA: a decision theoretic model.

Systematic analysis of the genetic background of complex diseases using single nucleotide polymorphisms (SNPs) affords a tremendous amount of genotypings. To reduce the amount of genotypings necessary and hence the overall cost of a case-control study with SNPs, the genotyping is often performed in two stages. In the first, the DNA of all cases and all controls are mixed into two pools and genotyped for each SNP. The frequency of both alleles is determined in both pooled DNA samples. If different frequencies are observed in the pools of cases and controls, genotyping is performed individually in the second stage and analyzed conventionally. However, so far no well-founded algorithm is available to guide the decision on whether to genotype a SNP individually. In this report, an approach is introduced for the decision on individual genotyping based on the results from pooled DNA. The analysis is modeled as a decision process with the specific goal to decide on whether to genotype a specific SNP individually. For a given situation, the resulting decision criteria are aimed to be optimal for those conducting the study. Different loss functions and decision rules are presented. Using Monte-Carlo simulations, we show that for a given situation, the genotyping rates and hence the costs can be reduced remarkably while maintaining acceptable overall error rates.

Case-Control Studies↗
PubMed2006

Relationship between neurokinin 2 receptor gene polymorphisms and serum vascular endothelial growth factor levels in patients with toluene diisocyanate-induced asthma.

BACKGROUND: Among the various pathogenic mechanisms of toluene diisocyanate (TDI)-induced asthma, a contribution from neurogenic inflammation has been suggested. OBJECTIVE: To evaluate neurokinin 2 receptor (NK2R) gene polymorphisms in association with the clinical phenotype of TDI-induced asthma, 70 TDI-induced occupational asthma (TDI-OA)patients, 59 asymptomatic exposed controls (AEC), and 93 unexposed healthy controls (NC) were enrolled in the study. METHODS: Two single-nucleotide polymorphisms (SNPs) of NK2R, 7853G>A (Gly231Glu) and 11 424G>A (Arg375His), were genotyped using a single base extension method. The levels of PC20 methacholine, specific IgE and IgG to TDI-human serum albumin conjugate, and serum vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and TGF-beta1 were compared according to the NK2R genotypes of the subjects with TDI-OA and AEC. RESULTS: No significant differences in allele, genotype, or haplotype frequencies of these two SNPs were noted among the three groups (P>0.05, respectively). Moreover, subjects with the NK2R 7853GG genotype had higher serum VEGF levels than those with GA or AA among the TDI-exposed workers (P=0.040). CONCLUSION: The NK2R 7853GG genotype may contribute to increased serum VEGF levels, which result in airway inflammation after TDI exposure.

Adult↗
PubMed2004

Comparative analyses of four different methods of genotyping ALDH2.

BACKGROUND: A number of methods of genotyping single nucleotide polymorphisms (SNPs) are currently available, ranging from the traditional restriction fragment length polymorphism (RFLP) and single-stranded conformational polymorphism (SSCP) to more sophisticated technologies. We determined the utility of three novel methods by genotyping aldehyde dehydrogenase-2 (ALDH2). METHODS: DNA was isolated from blood samples of 241 control subjects and 74 patients with esophageal cancer. The utility of three novel genotyping methods-melting curve analysis using a LightCycler, SNaPshot analysis using an ABI PRISM 310 genetic analyzer, and denaturing high-performance liquid chromatography using a WAVE DNA fragment analysis system-were compared with that of conventional fluorescent-based polymerase chain reaction (PCR)-SSCP using an ALF express DNA sequencer. RESULTS: The frequency of the mutant ALDH2*2 allele was significantly higher in patients with esophageal cancer (27.7%) than in control subjects (16.2%; p < 0.01; habitual alcohol drinkers). The melting curve analysis was accurate, more rapid, and easier to use than the SNaPshot analysis or denaturing high-performance liquid chromatography analysis. Fluorescent-based PCR-SSCP proved useful for analyzing a large number of samples. CONCLUSION: Melting curve analysis using the LightCycler is suitable for the genotyping of small numbers of samples in a routine clinical setting; fluorescent-based PCR-SSCP analysis using the ALF express DNA sequencer can be used for large-scale genotyping in epidemiologic studies.

Adult↗
PubMed2005

PupasView: a visual tool for selecting suitable SNPs, with putative pathological effect in genes, for genotyping purposes.

We have developed a web tool, PupasView, for the selection of single nucleotide polymorphisms (SNPs) with potential phenotypic effect. PupasView constitutes an interactive environment in which functional information and population frequency data can be used as sequential filters over linkage disequilibrium parameters to obtain a final list of SNPs optimal for genotyping purposes. PupasView is the first resource that integrates phenotypic effects caused by SNPs at both the translational and the transcriptional level. PupasView retrieves SNPs that could affect conserved regions that the cellular machinery uses for the correct processing of genes (intron/exon boundaries or exonic splicing enhancers), predicted transcription factor binding sites and changes in amino acids in the proteins for which a putative pathological effect is calculated. The program uses the mapping of SNPs in the genome provided by Ensembl. PupasView will be of much help in studies of multifactorial disorders, where the use of functional SNPs will increase the sensitivity of the identification of the genes responsible for the disease. The PupasView web interface is accessible through http://pupasview.ochoa.fib.es and through http://www.pupasnp.org.

Computer Graphics↗
PubMed2003

Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome.

OBJECTIVE: To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case-control study. SETTING: University-based clinic. PATIENT(S): One hundred twelve white women with PCOS and 115 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURES: The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm. RESULT(S): Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8). CONCLUSION(S): The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.

Case-Control Studies↗
PubMed2006

Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patients.

Mismatch repair (MMR) genes are among of the most important genes associated with colorectal cancer (CRC). Single-nucleotide polymorphisms (SNPs) are generally thought to provide important information across a wide spectrum of life sciences; however, no study of association between SNPs of MMR genes and Chinese sporadic colorectal cancer (SCRC) is available. We chose 29 reported single-nucleotide variants that have rarely been verified in a population-based study. We identified SNPs and the genotype-phenotype association in Chinese populations of 150 healthy individuals and 160 SCRC patients. We extracted the genomic DNA from the blood of these individuals and used sequencing to determine these SNPs. Three SNPs (MLH1 394G-->C, 655A-->G, 1151T-->A) occurred with a frequency of 8.8-11.2% in the Chinese population. These SNPs formed a series with combined effects. The haplotype of concurrent MLH1 655 and 1151 SNPs and the haplotype combinations of MLH1 1151, MLH1 394 occurred exclusively in SCRC. None of the other 26 variants were detected in the Chinese population.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Haplotypes extending across ACE are associated with Alzheimer's disease.

Numerous genes have been implicated in Alzheimer's disease (AD), but, with the exception of a demonstrated association with the epsilon 4 allele of APOE, findings have not been consistently replicated across populations. One of the most widely studied is the gene for angiotensin I converting enzyme (ACE ). A meta-analysis of published data on a common Alu indel polymorphism in ACE was performed which indicated highly significant association of the insertion allele with AD (OR 1.30; 95% CI 1.19 - 1.41; P=4 x 10(-8)). To further explore the influence of ACE on AD, several single-nucleotide polymorphisms (SNPs) were genotyped in five independent populations represented by over 3100 individuals. Analyses based upon single markers and haplotypes revealed strong evidence of association in case-control models and also in a model examining the influence of variation in ACE upon cerebrospinal fluid levels of amyloid beta42 peptide (Abeta42). The most significant evidence for association with AD was found for an SNP, A-262T, located in the ACE promoter (OR 1.64; 95% CI 1.33 -1.94; P=2 x 10(-5)). Estimates of population attributable risk for the common allele of this SNP suggest that it, or an allele in tight linkage disequilibrium (LD) with it, may contribute to as much as 35% of AD in the general population. Results support a model whereby decreased ACE activity may influence AD susceptibility by a mechanism involving beta-amyloid metabolism.

Aged↗
PubMed2004

Toll-like receptor 4 gene polymorphisms and susceptibility to juvenile idiopathic arthritis.

OBJECTIVES: To determine if polymorphisms within the Toll-like receptor 4 (TLR4) gene are associated and linked with juvenile idiopathic arthritis (JIA). To investigate any possible gene-gene (epistatic) interaction between TLR4 and macrophage migration inhibitory factor (MIF) gene polymorphisms. METHODS: 313 simplex families (each containing one affected JIA proband) were genotyped. Two known functionally important single nucleotide polymorphisms (SNPs) within the TLR4 gene (Asp299Gly and Thr399Ile) were typed by SNaPshot ddNTP primer extension and capillary electrophoresis. Single point and multipoint transmission disequilibrium tests (TDT) were carried out through the extended TDT and TDT phase packages for the two TLR4 SNPs. Epistatic interaction between TLR4 haplotypes and the previously JIA associated MIF CATT(7)-MIF-173*C promoter haplotype was investigated by chi(2) test and unconditional logistic regression in Stata version 7. RESULTS: No distortion from random inheritance was observed by single point analysis for TLR4 Asp299Gly (p = 0.89) or TLR4 Thr399Ile (p = 0.40). Similarly, no distortion in transmission was seen when the TLR4 haplotypes were studied (p = 0.54). Additionally, no evidence for gene-gene interaction between TLR4 polymorphisms and the previously associated MIF gene polymorphisms was found (p = 0.40). CONCLUSIONS: No linkage or association was seen for Asp299Gly or Thr399Ile SNPs of TLR4 with JIA susceptibility. No evidence of an epistatic interaction between these TLR4 polymorphisms and MIF polymorphisms was found.

Adolescent↗
PubMed2006

The admixture maximum likelihood test: a novel experiment-wise test of association between disease and multiple SNPs.

Disease association studies often test large numbers of markers, and various methods have been proposed to correct for multiple testing. In this paper, we propose an admixture maximum likelihood approach that estimates both the proportion of associated single nucleotide polymorphisms (SNPs) and their typical effect size. We assessed this method and compared it with several previously proposed approaches by simulation. The maximum likelihood approach performed similarly to or better than all other tests across a wide range of alternative hypotheses. The rank truncated product method also had good power, though somewhat inferior to the maximum likelihood approach in most cases. A simple Bonferroni correction performed best only when the number of associated SNPs was small.

Genetic Predisposition to Disease↗
PubMed2005

A simple, bead-based approach for multi-SNP molecular haplotyping.

Single nucleotide polymorphisms (SNPs) within a gene region have often been studied to determine their effect on phenotype. Although a single base pair change can produce a phenotypic change, phenotype is often influenced by the presence of multiple polymorphisms and their relative positions within a given region. For example, if multiple changes occur in a promoter region, how they influence gene expression will depend on their cis/trans configuration. As such, it is essential to consider the haplotype, or the alignment of multiple SNP alleles on each chromosome when attempting to associate genomic changes with phenotype. Unfortunately, no method of high-throughput molecular haplotyping of multiple SNPs currently exists. In response to this unmet need, we have developed an inexpensive, reliable bead-based capture-based haplotyping (CBH) assay to determine the phase, or haplotype, of multiple SNP alleles in a high-throughput manner. The CBH assay requires minimal setup and handling, requires no centrifugation steps and can be performed in <1 h. Data collection is performed via flow cytometry and the assay yields plus/minus results allowing for automated calling by a simple computer application. We will present data demonstrating the molecular haplotyping of 11 SNPs within exon 2 of the N-acetyltransferase-2 (NAT2) gene, which expresses an important drug-metabolizing enzyme. This assay has applications in diagnostic testing, promoter analysis, association studies and pharmacogenetic analysis.

Arylamine N-Acetyltransferase↗
PubMed2006

Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy.

DNA repair enzymes repair DNA damaged by platinum agents and ionising radiation. Single nucleotide polymorphisms (SNPs) in DNA repair genes modulate the repair capacity and might affect response and prognosis following platinum-based chemoradiotherapy (CRT). We investigated associations between the functional SNPs in DNA repair genes and response and survival in muscle-invasive bladder cancer patients treated with CRT to determine the predictive value of the SNPs in patient selection for bladder conservation therapy. The study group comprised 78 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms in xeroderma pigmentosum complementation groups C (Lys939Gln, A/C), D (XPD; Lys751Gln, A/C), and G (Asp1104His, G/C), and X-ray repair cross-complementing groups 1 (XRCC1; Arg399Gln, G/A) and 3 (Thr241Met, T/C) genes were genotyped. Combined genotypes with at least one variant allele in XPD or XRCC1 were significantly associated with improved cancer-specific survival compared with remaining groups (P=0.009). In multivariate analysis, only the combined XPD and XRCC1 genotypes were independently associated with cancer-specific survival (P=0.04). The association was stronger in stage T3/T4 patients (P=0.0008). These results suggest that combined XPD and XRCC1 genotypes might be prognostic factors in muscle-invasive bladder cancer patients treated with CRT.

Aged↗
PubMed2004

Further investigation of linkage disequilibrium SNPs and their ability to identify associated susceptibility loci.

There is currently considerable interest in the use of single-nucleotide polymorphisms (SNPs) to map disease susceptibility genes. The success of this method will depend on a number of factors including the strength of linkage disequilibrium (LD) between marker and disease loci. We used a data set of SNP genotypings in the region of the APOE disease susceptibility locus to investigate the likely usefulness of SNPs in case-control studies. Using the estimated haplotype structure surrounding and including the APOE locus, and assuming a codominant disease model, we treated each SNP in turn as if it were a disease susceptibility locus and obtained, for each disease locus and markers, the expected likelihood ratio test (LRT) to assess disease association. We were particularly interested in the power to detect association with the susceptibility polymorphism itself, the power of nearby markers to detect association, and the ability to distinguish between the susceptibility polymorphism and marker loci also showing association. We found that the expected LRT depended critically on disease allele frequencies. For disease loci with a reasonably common allele we were usually able to detect association. However, for only a subset of markers in the close neighbourhood of the disease locus was association detectable. In these cases we were usually, but not always, able to distinguish the disease locus from nearby associated marker loci. For some disease loci, no other loci demonstrated detectable association with the disease phenotype. We conclude that one may need to use very dense SNP maps in order to avoid overlooking polymorphisms affecting susceptibility to a common phenotype.

Alzheimer Disease↗
PubMed2003

Maximum likelihood and Bayesian methods for estimating the distribution of selective effects among classes of mutations using DNA polymorphism data.

Maximum likelihood and Bayesian approaches are presented for analyzing hierarchical statistical models of natural selection operating on DNA polymorphism within a panmictic population. For analyzing Bayesian models, we present Markov chain Monte-Carlo (MCMC) methods for sampling from the joint posterior distribution of parameters. For frequentist analysis, an Expectation-Maximization (EM) algorithm is presented for finding the maximum likelihood estimate of the genome wide mean and variance in selection intensity among classes of mutations. The framework presented here provides an ideal setting for modeling mutations dispersed through the genome and, in particular, for the analysis of how natural selection operates on different classes of single nucleotide polymorphisms (SNPs).

Bayes Theorem↗
PubMed2004

Mutation detection in the drug-resistant hepatitis B virus polymerase gene using nanostructured reverse micelles.

The emergence of drug-resistant hepatitis B virus (HBV) has been reported in patients with prolonged administration of lamivudine, which is a potent drug for the prevention of HBV infection. Lamivudine-resistant HBV has several types of mutations at the YMDD motif of its DNA polymerase. We successfully demonstrated that monitoring the hybridization behavior in nanostructured reverse micelles enables us to detect single nucleotide polymorphisms (SNPs). With the aid of reverse micelles, a model 40-mer oligonucleotide containing a single-base substitution was clearly distinguished from the normal, complementary oligonucleotide. In addition, we extended this technique to a high-throughput analysis. The results obtained with a 96-well micro-plate reader indicated the possibility of SNPs detection toward multiple samples of patients.

Anti-HIV Agents↗
PubMed2001

[Clinical significance and strategies to analyze genetic polymorphisms].

A DNA polymorphism can be defined as a difference in the primary sequence of DNA, and the frequency of the rarer allele among the general population exceeds 1%. Several types of polymorphisms, including minisatellite and microsatellite markers, deletion or insertion of short nucleotide sequences, and single nucleotide polymorphisms(SNPs), are present in human genome, with different frequencies and different distribution patterns. SNPs are very common and clinically important, because they often appear within genes, particularly within coding sequences. The biological significance of a polymorphism differs significantly depending upon its location within the genome. For example, polymorphisms located outside genes usually do not have biological consequences, and will be used merely as markers for genetic linkage. On the other hand, those located within a gene may cause subtle changes in transcription, mRNA stability, or protein conformation if amino acid substitution occurs. These subtle changes in biologically important factors then alter susceptibility to certain disorders. Environmental factors often interact with genes. Relationships between genetic polymorphisms and disease susceptibility have been reported on many kinds of human diseases, including neurological and psychiatric disorders, infectious diseases, endocrine and metabolic disorders, malignancy, as well as cardiovascular diseases. Recent years have seen the progress in novel strategies for rapid genotyping of a large numbers of polymorphisms, and also, for searching unknown SNPs.

Genetic Predisposition to Disease↗