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Results for “Single nucleotide polymorphisms”

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At least 433 records · Page 24Linked 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↗
PubMed2003

Multiplex single-nucleotide polymorphism genotyping by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A robust high-throughput single-nucleotide polymorphism (SNP) genotyping method is reported, which applies allele-specific extension to achieve allelic discrimination and uses matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to measure the natural molecular weight difference of oligonucleotides for determination of the base in a single-nucleotide polymorphic location. Tenfold PCR is performed successfully by carefully designing the primers and adjusting the conditions of PCR. In addition, two ways used for PCR product purification are compared and the matrix used in mass spectrometry for high-throughput oligonucleotide analysis is evaluated. The result here shows that the method is very effective and suitable for high-throughput genotyping of SNPs.

DNA Primers↗
PubMed2006

[Study of single nucleotide polymorphism of A-FABP gene and its association with fatness traits in chicken].

In this experiment, Beijing-You chicken was used to detect single nucleotide polymorphisms (SNPs) in A-FBAP gene and to study the correlation between its genotype and the trait of fat accumulation. The first exon of the gene was amplified by one pair of primers, and SNPs were detected by the technique of single strand conformation polymorphism (SSCP) and finally confirmed by sequencing. Results of analysis of variance showed that a significant difference existed among abdominal fat percentage, subcutaneous fat thickness and intramuscular fat contents in breast musculature with different genotypes (P<0.01). It implied that A-FABP gene could be a major effector gene or could be linked to gene(s) which significantly affect fat metabolism in chicken.

Adipocytes↗
PubMed2000

Single nucleotide polymorphisms (SNPs) within Bov-A2 SINE in the second intron of bovine and buffalo k-casein (CSN3) gene.

The genetic polymorphism of an entire Bov-A2 element located in the second intron of the buffalo and bovine k-casein (CSN3) gene was investigated by amplification and sequencing of PCR products. Single nucleotide polymorphisms were detected. A PCR-RFLP method was developed to detect an A or G mutation at position 605 of bovine Bov-A2 element which creates a BfaI polymorphic site. The frequencies of the B allele, with the BfaI site, were for 0.275, 0.775, 0.750, 0.975, respectively, for Italian Holstein Friesian, Grey Alpine, Friuli Red Pied and Reggio bovine breeds. The mutation rate (substitutions and deletions/insertions per nucleotide site per year) was 2.5 x 10(-9) for Bov-A2 sequences in the second intron of CSN3. The comparison with other Bov-A2 elements suggests that this retroelement might be an important source of single nucleotide polymorphism for analysis of Bovidae genomes.

Animals↗
PubMed1999

Single-nucleotide polymorphisms can cause different structural folds of mRNA.

Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation in man. Genes containing one or more SNPs can give rise to two or more allelic forms of mRNAs. These mRNA variants may possess different biological functions as a result of differences in primary or higher order structures that interact with other cellular components. Here we report the observation of marked differences in mRNA secondary structure associated with SNPs in the coding regions of two human mRNAs: alanyl tRNA synthetase and replication protein A, 70-kDa subunit (RPA70). Enzymatic probing of SNP-containing allelic fragments of the mRNAs revealed pronounced allelic differences in cleavage pattern at sites 14 or 18 nt away from the SNP, suggesting that a single-nucleotide variation can give rise to different mRNA folds. By using phosphorothioate oligodeoxyribonucleotides complementary to the region of different allelic structures in the RPA70 mRNA, but not extending to the SNP itself, we find that the SNP exerts an allele-specific effect on the accessibility of its flanking site in the endogenous human RPA70 mRNA. This further supports the allele-specific structural features identified by enzymatic probing. These results demonstrate the contribution of common genetic variation to structural diversity of mRNA and suggest a broader role than previously thought for the effects of SNPs on mRNA structure and, ultimately, biological function.

Alanine-tRNA Ligase↗
PubMed2002

Large-scale genotyping of single nucleotide polymorphisms by Pyrosequencingtrade mark and validation against the 5'nuclease (Taqman((R))) assay.

Here we present the first large-scale effort at genotyping using a novel sequencing method, Pyrosequencingtrade mark, as a method for genotyping of single nucleotide polymorphisms (SNPs). Pyrosequencingtrade mark genotypes were validated through duplicate analysis of 1,022 genotypes using the PSQ96trade mark instrument for pyrosequencing and TaqMan((R)) for 5'nuclease assays. Identical results were obtained using both methods. In a small pilot study, a pooling strategy using Pyrosequencingtrade mark was successfully tested. We conclude that Pyrosequencingtrade mark is highly efficient and accurate in the analysis of SNPs and represents a promising solution to high-throughput genotyping of large sample populations.

Alleles↗
PubMed2001

PIRA PCR designer for restriction analysis of single nucleotide polymorphisms.

UNLABELLED: Primer-introduced restriction analysis (PIRA-PCR) is widely used to detect Single Nucleotide Polymorphisms (SNPs). To create artificial Restriction Fragment Length Polymorphism (RFLP), a mismatch is usually introduced near the end of the primer that is close to the mutation of interest. We describe in this report a www-based computer program that screens for the suitable mismatches, designs the primers, lists the appropriate restriction enzymes and other related information. AVAILABILITY: The computer program, with related descriptions, is available at http://cedar.genetics.soton.ac.uk/public_html/primer2.html.

Base Pair Mismatch↗
PubMed2004

Single nucleotide polymorphism analysis on melanocortin receptor 1 (MC1R) of Chinese native pig.

Melanocortin receptor 1 (MC1R) gene, one of the important candidate genes for coat color trait, was used to analyze the single nucleotide polymorphism (SNP) in Chinese native pig breeds by PCR-single strand conformation polymorphism (PCR-SSCP). The study had also taken 3 imported pig breeds as control. The results showed that the three mutations G284A, T309C and T364C found in Chinese native pigs were consistent to the mutation found in the European Large Black individuals. However, 68CC or C492T and G728A were only found in the imported individuals, which were obviously different from the Chinese native pigs. Accordingly, we presumed that the coat colors of Chinese native pigs belonged to dominant black color system, which was completely distinct to that of imported pig breeds. Thus it was implied that MC1R gene was not the principal factor affecting the coat color differences of Chinese native pig breeds, but could be used to trace the molecular evolution of pig breeds.

Animals↗
PubMed2006

Single nucleotide polymorphism array analysis to predict clinical outcome in neuroblastoma patients.

PURPOSE: Neuroblastoma (NB) is a heterogeneous tumor and demonstrates favorable or unfavorable outcomes. In Japan, a nationwide NB mass screening (MS) had been performed on 6-month-old infants for approximately 20 years, which might have detected almost all NB including regressing/maturing tumors. To clarify the heterogeneity of this tumor, we examined genetic alterations in the representative cases using genomewide microarrays. METHODS: Genomic DNA was extracted from 198 NB tissue samples and paired blood samples including 76 MS-detected cases and analyzed by single nucleotide polymorphism arrays. RESULTS: The single nucleotide polymorphism array classified the genetic aberrations into 4 types: whole gain/loss type, partial gain/loss type, MYCN-amplified type, and silent type. Most MS-detecting cases belonged to the whole gain/loss type, whereas unfavorable cases who died of disease showed partial gain/loss, MYCN-amplified, or silent types. CONCLUSIONS: Genomewide genetic analysis is useful to predict the outcome of patients. Although the cases whose tumors showed whole gain/loss may respond well to contemporary therapy, sparing intensive surgery, current therapeutic strategy may be insufficient for the subgroups with partial gain/loss, MYCN-amplified, or silent type. Validation of these results would provide new tools to predict clinical outcome of children with NB.

Adolescent↗
PubMed2001

Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes.

AIMS/HYPOTHESIS: AKT1, a serine/threonine protein kinase, is an important downstream target of the insulin-signalling pathway, with both anti-apoptotic and peripheral metabolic effects. Because impaired insulin signalling is a major hallmark of Type II (non-insulin-dependent) diabetes mellitus, we considered whether the AKT1 gene could be a candidate gene involved in susceptibility of this condition. To test this possibility, we isolated and characterized the human AKT1 gene. We also looked for single nucleotide polymorphisms in the gene and examined their association with Type II diabetes mellitus in the Ashkenazi Jewish population. METHODS: Human BAC/P1 genomic libraries were screened to isolate the AKT1 gene. To obtain structural information and the sequences of the exon-intron boundaries, BAC/P1 clones were directly sequenced. Identification of single nucleotide polymorphisms was done by polymerase chain reaction of each exon, followed by denaturing high performance liquid chromatography. Six single nucleotide polymorphisms were genotyped in Ashkenazi Jewish patients with Type II diabetes mellitus and in control subjects. RESULTS: The human AKT1 gene was at least 24.6 kb in length and comprised 14 exons. Altogether 13 putative intragenic single nucleotide polymorphisms, with minor-allele frequencies ranging from 0.011 to 0.354, were identified. The allelic and the genotypic frequencies of 6 single nucleotide polymorphisms were the same in diabetic patients and in control subjects. CONCLUSION/INTERPRETATION: The results of our studies show that the AKT1 gene is not a major contributor to susceptibility to Type II diabetes mellitus in Ashkenazi Jews.

Base Sequence↗
PubMed2004

Genotyping using single nucleotide polymorphism, fluorescence spectroscopy and pattern recognition.

This paper describes a method for genetic screening using single nucleotide polymorphism. Fluorescence spectra with an excitation frequency of 488 nm are recorded over a range of 550 to 660 nm of fragments of human DNA together with two fluorescent probe dyes attached to specific primers, one for each type of allele and a background dye, prepared using the Taqman reaction. The fluorescence spectra are monitored and principal components analysis used to separate spectra into three groups, which are visually identified as allele 1 (wild type), allele 2 (mutant) and mixed allele by comparison to reference samples. Malahanobis distance using 4 principal components are used to correctly classify samples into groups.

DNA↗
PubMed2005

Screening for deleterious nonsynonymous single-nucleotide polymorphisms in genes involved in steroid hormone metabolism and response.

To facilitate selection of single-nucleotide polymorphisms (SNP) for molecular epidemiologic studies investigating the hormonal carcinogenesis hypothesis, we used two sequence homology-based tools [Sort Intolerant from Tolerant (SIFT) and Polymorphism Phenotype (PolyPhen)] to predict the potential impact a nonsynonymous SNP (nsSNP), which results in an amino acid substitution, may have on the activity of proteins encoded by genes involved in the steroid hormone metabolism and response pathway. We screened 137 variants. Of these, 28% were predicted by SIFT and PolyPhen as having a potentially damaging effect on protein function. Investigation into the association of these variant alleles with hormone-related cancers may prove to be fruitful.

Algorithms↗
PubMed2002

Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms.

Escherichia coli O157:H7 (O157) strains demonstrate varied pulsed-field gel electrophoresis patterns following XbaI digestion, which enable epidemiological surveillance of this important human pathogen. The genetic events underlying PFGE differences between strains, however, are not defined. We investigated the mechanisms for strain variation in O157 by recovering and examining nucleotide sequences flanking each of the XbaI restriction enzyme sites in the genome. Our analysis demonstrated that differences between O157 strains were due to discrete insertions or deletions that contained the XbaI sites polymorphic between strains rather than single-nucleotide polymorphisms in the XbaI sites themselves. These insertions and deletions were found to be uniquely localized within the regions of the genome that are specific to O157 compared to E. coli K-12 (O islands), suggesting that strain-to-strain variation occurs in these O islands. These results may be utilized to devise novel strain-typing tools for this pathogen.

Chromosomes, Bacterial↗
PubMed2005

Application of family-based association testing to assess the genotype-phenotype association involved in complex traits using single-nucleotide polymorphisms.

BACKGROUND: We used the FBAT (family-based association test) software to test for association between 300 individual single-nucleotide polymorphisms and P1 (a latent trait of Kofendred Personality Disorder) in 100 simulated replicates of the Aipotu population. Using the Genetic Analysis Workshop 14 dataset, we calculated the power of FBAT to detect linkage disequilibrium on chromosome 3 (D2). Also, we calculated the false-positive rate on chromosome 1, which contains a true locus (D1) but no linkage disequilibrium was simulated between the trait and all the surrounding single-nucleotide polymorphisms. RESULTS: We were able to detect the associations between phenotype P1 and three adjacent markers B03T3056 (average p-value = 0.0002), B03T3057 (average p-value = 0.00072), and B03T3058 (average p-value = 0.0038) with power of 98%, 87%, 71% on chromosome 3, respectively. The overall false positive rate to detect association was 0.06 on chromosome 1. CONCLUSION: The power to detect a significant association in 100 nuclear families affected with the latent trait of Kofendred Personality Disorder by using FBAT was reasonable (based on 100 replicates). In the future, we will compare the performance of FBAT with alternative approaches, such as using FBAT-generalized estimating equations methods to test for association in families affected with complex traits.

Chromosomes, Human, Pair 1↗
PubMed2005

A method for finding single-nucleotide polymorphisms with allele frequencies in sequences of deep coverage.

BACKGROUND: The allele frequencies of single-nucleotide polymorphisms (SNPs) are needed to select an optimal subset of common SNPs for use in association studies. Sequence-based methods for finding SNPs with allele frequencies may need to handle thousands of sequences from the same genome location (sequences of deep coverage). RESULTS: We describe a computational method for finding common SNPs with allele frequencies in single-pass sequences of deep coverage. The method enhances a widely used program named PolyBayes in several aspects. We present results from our method and PolyBayes on eighteen data sets of human expressed sequence tags (ESTs) with deep coverage. The results indicate that our method used almost all single-pass sequences in computation of the allele frequencies of SNPs. CONCLUSION: The new method is able to handle single-pass sequences of deep coverage efficiently. Our work shows that it is possible to analyze sequences of deep coverage by using pairwise alignments of the sequences with the finished genome sequence, instead of multiple sequence alignments.

Computers, Molecular↗
PubMed2002

Single nucleotide polymorphisms derived from ancestral populations show no evidence for biased diversity estimates in Drosophila melanogaster.

Single nucleotide polymorphisms (SNPs) are about to become one of the most popular genetic markers for genetic model organisms. To test the usefulness of SNPs for estimating genetic diversity, we surveyed three genomic regions in two Drosophila melanogaster populations, one from Africa and one European, collected in Austria. Diversity estimates based on the full SNP set indicated higher levels of variability in the African than in the European flies. When the analysis was based on the European SNP set, European and African flies had similar levels of variability. Interestingly, this bias was not observed for diversity estimates using SNPs derived from the ancestral African population. This result suggests that diversity estimates based on SNPs from ancestral populations could provide a general strategy to avoid biased SNP diversity estimates. Finally, the potential of SNPs for nonmodel organisms is discussed.

Animals↗
PubMed2006

Rapid melting curve analysis on monolayered beads for high-throughput genotyping of single-nucleotide polymorphisms.

This report describes a rapid solid-phase melting curve analysis method for single-nucleotide polymorphism (SNP) genotyping. The melting curve analysis is based on dynamic allele-specific hybridization (DASH). The DNA duplexes are conjugated on beads that are immobilized on the surface of a microheater chip with integrated heaters and temperature sensors. SNP on PCR products were scored, illustrating the sensitivity and robustness of the system. The method is based on random bead immobilization by microcontact printing. Single-bead detection and multiplexing were performed with a heating rate more than 20 times faster than conventional DASH. Analyses that took more than 15 min could be performed in less that 1 min, enabling ultrarapid SNP analysis. In addition, an array version of the chip was implemented enabling the preparation of an array of bead arrays for high-throughput and rapid SNP genotyping.

Alleles↗