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Results for “Single nucleotide polymorphisms”

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PubMed2004

Typing single-nucleotide polymorphisms in Toxoplasma gondii by allele-specific primer extension and microarray detection.

Genotyping is an important tool for epidemiological and population genetic studies in protozoan parasites. The most commonly used method for genotyping is polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis of single nucleotide polymorphisms (SNPs). However, PCR-RFLP analysis is labor intensive, and only a proportion of the SNPs are recognized by currently available restriction enzymes. Here, we have developed a more efficient microarray-based method to genotype SNPs in the protozoan parasite Toxoplasma gondii. This method is sensitive, accurate, and capable of analyzing multiple SNPs simultaneously in a high-throughput format.

Alleles↗

PubMed2005

Construction of an electrochemical DNA chip for simultaneous genotyping of single nucleotide polymorphisms.

An electrochemical DNA chip was constructed for simultaneous genotyping of single nucleotide polymorphisms (SNPs) using genomic DNA extracted from blood samples. This chip consisted of electrodes located on a single piece of substrate and allele-specific oligonucleotide probes on the electrodes. As a first application, the 4 SNPs (MxA[-88], MxA[-123], MBL[X/Y], and MBL[A/B]), which have association with the efficacy of interferon therapy for HCV patient, were genotyped on the new DNA chip. Following hybridization of PCR products containing the 4 types of fragments, washing, bisbenzimide H33258 (Hoechst 33258) reaction and electrochemical analyses, 59 blood samples were genotyped by the chip method simultaneously. All procedures were completed within 2 h and the results were 100% concordant with those by the direct sequence method. The electrochemical DNA chip is expected to be a practical tool for SNPs genotyping.

Bisbenzimidazole↗

PubMed1999

Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus.

Interleukin-10 (IL-10) is a pivotal immunoregulatory cytokine, influencing many aspects of the immune response. The IL-10 gene is located on chromosome 1 at 1q31-32 and is highly polymorphic. One microsatellite and three single nucleotide polymorphisms (SNPs) have been recorded within the 1.2 kb immediately upstream of the gene, with an additional microsatellite present at 4 kb upstream. The relationship between these two classes of polymorphism is poorly defined in the IL-10 gene. Haplotypes have been presented comprising alleles from the two microsatellite loci, and independently from the three SNPs, but these have not yet been brought together to define unified halpotypes. In the present report we describe the 29 IL-10 haplotypes found in 56 Dutch European families and show that they fall into four major haplotype groups, each of which spans the 4 kb upstream of the IL-10 gene and has a different distribution of IL10.G alleles. In addition, we describe three novel single nucleotide polymorphisms in the human IL-10 gene and suggest how they relate to these four haplotype families.

Alleles↗

PubMed2003

CYP3A53 and 6 single nucleotide polymorphisms in three distinct Asian populations.

OBJECTIVE: To determine the frequencies of two functional single nucleotide polymorphisms, CYP3A5*3 and CYP3A5*6, in the CYP3A5 gene in three distinct Asian ethnic groups, namely, the Chinese, Malays and Indians. METHODS: Single nucleotide polymorphism analyses of CYP3A5*1, *3 and *6 were performed in 296 healthy subjects (108 Chinese, 98 Malays and 90 Indians) using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The *1 allele frequency was 25% in Chinese compared with 40% in Malays and Indians ( P=0.001). The *3 allele frequency was also higher in the Chinese population, being 76% versus 60% in the Malays and Indians ( P=0.001). The Malays and Indians also had allele frequencies significantly different from Caucasian, Japanese and African-American populations (each P<or=0.001) previously published in the literature. The *6 allele was not detected in any the three Asian ethnic groups analysed. CONCLUSION: These results seem to suggest that genetic polymorphisms in CYP3A5 in Asians, in particular Malays and Indians but also Chinese although to a lesser extent, may be an important genetic contributor to interindividual as well as interethnic differences in clearance of CYP3A substrates.

Asian People↗

PubMed2005

Modeling the effect of an associated single-nucleotide polymorphism in linkage studies.

For linkage analysis in affected sibling pairs, we propose a regression model to incorporate information from a disease-associated single-nucleotide polymorphism located under the linkage peak. This model can be used to study if the associated single-nucleotide polymorphism marker partly explains the original linkage peak. Two sources of information are used for performing this task, namely the genotypes of the parents and the genotypes of the siblings. We applied the methods to three significantly disease-associated single-nucleotide polymorphisms and five microsatellite markers at the end of chromosome 3 of replicate 1 of Aipotu population. Two out of five of the microsatellite markers showed a LOD score higher than 3. The question to be answered was whether one of the single-nucleotide polymorphisms partly explains these high LOD scores. We did not have the answers when we analyzed the data.

Chromosomes, Human, Pair 3↗

PubMed2002

High-throughput single-nucleotide polymorphism genotyping by fluorescent competitive allele-specific polymerase chain reaction (SNiPTag).

Single nucleotide polymorphisms (SNPs) are becoming widely recognized as the new currency for gene mapping as increasing numbers are discovered. Here we outline a method for their rapid analysis based on an allele-specific polymerase chain reaction (PCR) which employs a competitive approach, whereby both allele-specific primers are present in the same reaction and carry different fluorescent labels. This procedure is simple and amenable to high-throughput genotyping using conventional automated sequencing equipment, and no post-PCR modifications are required. Verification of the procedure was carried out by comparison of results derived by this method with those from restriction enzyme digestion of the ALDH2 exon 12 functional polymorphism (Glu-487-Lys) in 109 individuals. Additionally, we have examined all combinations of nucleotide substitutions and shown them to be differentiated by this method. As proof of concept, several assays were combined and loaded on a single gel lane/capillary to substantially improve throughput. This was made possible by designing the PCR products to be of different lengths and no interference was observed between products differing in size by only six nucleotides. We outline a number of test assays for well-characterized SNPs in human candidate genes for behavioral disorders.

Aldehyde Dehydrogenase↗

PubMed2003

Correlation of a single nucleotide polymorphism in the E-cadherin gene promoter with tumorigenesis and progression of gastric carcinoma in Japan.

A C/A single nucleotide polymorphism (SNP) in the E-cadherin gene promoter has been shown to affect transcriptional efficiency in vitro. In this study, we analyzed the C/A SNP in 106 gastric carcinoma cases and 90 cancer-free controls compared with clinicopathological parameters. The genotype of C/C, C/A, and A/A was found in 61 (58%), 34 (32%) and 11 (10%) of 106 gastric carcinoma cases and in 32 (36%), 52 (58%) and 6 (6%) of 90 cancer-free controls, respectively. The genotype of C/C was significantly more frequent in gastric carcinoma cases than in cancer-free controls (p<0.05). The E-cadherin protein expression level in non-neoplastic gastric mucosa was higher in the C/C genotype than in the C/A. In gastric carcinoma cases, the genotype of C/C was significantly more frequent in the cases of poorly differentiated adenocarcinoma (31/44; 70%) than in well differentiated type (30/62; 48%). The C/C genotype was also significantly more frequent in the cases with deep invasion (51/74; 69%) and with lymph node metastasis (38/54; 70%) than in those confined superficially (10/32; 31%) and without lymph node metastasis (23/52; 44%), respectively (p<0.05). These results suggest that the C/A SNP in the E-cadherin promoter may be a good marker for malignancy of gastric carcinomas.

Aged↗

PubMedDate not supplied

Association of p53 mutations and a codon 72 single nucleotide polymorphism with lower overall survival and responsiveness to adjuvant radiotherapy in endometrioid endometrial carcinomas.

p53 Genetic alterations are associated with advanced stage and aggressive tumors in a variety of human malignancies. The aim of this study was to examine p53 for genetic alterations and to evaluate the association of these alterations with clinical outcome and response to adjuvant radiotherapy in endometrioid endometrial carcinomas. p53 mutations in exons 2-11 were assessed in 59 endometrioid carcinomas by polymerase chain reaction-single-strand conformational polymorphism and sequence analysis. Twelve mutations (20.3%) and nine polymorphisms were identified. Seven of the nine polymorphisms were codon 72 single nucleotide polymorphisms (SNP) with an Arg/Pro allelotype. Women harboring either a mutation or an Arg/Pro allelotype at codon 72 had a lower overall survival rate than women whose tumors lacked alterations in the p53 gene (P= 0.0029). Women were stratified based on p53 genetic alterations (p53 mutation or p53 codon 72 SNP) and whether or not they received adjuvant radiation therapy. Women with p53 genetic alterations who did not receive adjuvant radiotherapy had the lowest survival rate (P= 0.0005). Treated women with p53 genetic alterations and untreated women with no p53 alteration had similar rates of survival. Among women with p53 alterations, adjuvant radiotherapy substantially increased survival (P= 0.035). In multivariate analyses, the group of women with p53 genetic alterations who did not receive adjuvant radiation therapy had a 5.9-fold increased risk of death (95% confidence interval: 1.5-22.7) compared to women whose tumors lacked p53 alterations and did not receive adjuvant radiation therapy.

Adult↗

PubMed2004

Estimation of relative allele frequencies of single-nucleotide polymorphisms in different populations by microarray hybridization of pooled DNA.

Single-nucleotide polymorphisms (SNPs) are considered useful polymorphic markers for genetic studies of polygenic traits. A new practical approach to high-throughput genotyping of SNPs in a large number of individuals is needed in association study and other studies on relationships between genes and diseases. We have developed an accurate and high-throughput method for determining the allele frequencies by pooling the DNA samples and applying a DNA microarray hybridization analysis. In this method, the combination of the microarray, DNA pooling, probe pair hybridization, and fluorescent ratio analysis solves the dual problems of parallel multiple sample analysis, and parallel multiplex SNP genotyping for association study. Multiple DNA samples are immobilized on a slide and a single hybridization is performed with a pool of allele-specific oligonucleotide probes. The results of this study show that hybridization of microarray from pooled DNA samples can accurately obtain estimates of absolute allele frequencies in a sample pool. This method can also be used to identify differences in allele frequencies in distinct populations. It is amenable to automation and is suitable for immediate utilization for high-throughput genotyping of SNP.

Gene Frequency↗

PubMedDate not supplied

Single-nucleotide polymorphism of the urokinase-plasminogen activator gene during aging and transformation of human diploid kidney cell cultures.

Single-nucleotide polymorphisms (SNPs) are differences in the nucleotide sequence of a specific gene from different individuals. The frequency at which SNPs occur varies among individuals, is gene dependent, and may be influenced by the aging process or by mechanisms that result in cell transformation. Urokinase-plasminogen activator (uPA) is a serine protease that is important in embryonic development, aging, and the onset of pathogenic conditions. The frequency of SNP and the stability of the SNPs in the uPA gene have not been defined with regard to processes that are associated with cellular aging or transformation. In this study, the complete nucleotide sequence has been determined for the gene encoding uPA from 26 human diploid kidney cell lines. The frequency of SNP occurrence within the uPA gene and whether this frequency changed during cellular aging, or after cell transformation, were determined. The results demonstrated three donor-dependent SNPs. One SNP was located at base pair 422, which is in the region of the gene responsible for encoding the high-molecular weight domain of uPA (HMW-uPA). The other SNPs were located at base pairs 691 and 822, both of which are in the region of the gene responsible for encoding the low-molecular weight domain of uPA (LMW-uPA). Single-nucleotide polymorphisms were not detected in the portion of the gene responsible for encoding the uPA secretion signal. Leucine or proline would be encoded at amino acid 141 of HMW-uPA as the result of an SNP at base pair 422. The SNP detected at base pair 691 would encode for lysine or glutamine at amino acid 231 of LMW-uPA. The SNP detected at base pair 822 would not change the encoded asparagine located at position 274 of the protein. The SNPs identified in this study were donor dependent and were not altered during cellular aging, or by changes in karyology due to spontaneous transformation of the cell line. These results demonstrate that the integrity of the uPA gene is stable and not subject to alterations that accompany cell aging or transformation.

Aging↗

PubMed2004

Single nucleotide polymorphism characterization by mRNA expression imbalance assessment.

The functional characterization of single nucleotide polymorphism (SNPs) represents a major challenge for pharmacogenetics and related research areas. Here, we propose a procedure, termed mRNA expression imbalance assessment, that can be applied to detect cis-acting SNPs with an effect on mRNA expression. The procedure is based on the observation that the relative transcript levels derived from the two alleles of an autosomal gene are reflected in the sequence of the amplified cDNA. The key element of the procedure is the detection of a discrepancy between the specific nucleotide signal intensity of a marker SNP in the genomic DNA and in the cDNA. We used the CYP3A5*1/*3 polymorphism as a proof principle for this approach. In this case, we could even demonstrate that the procedure works equally well with the appropriate tissue samples and in silico, using the existing databanks of sequences. In conclusion, the procedure provides a fast and easy tool, which may facilitate identification of functional SNPs.

Base Sequence↗

PubMed2004

[Single nucleotide polymorphisms and point mutations of ataxia telangiectasia mutated gene in Chinese of Han ethnicity].

OBJECTIVE: To explore the single nucleotide polymorphisms (SNPs) and point mutations of ataxia telangiectasia mutated (ATM) gene in Chinese of Han ethnicity. METHODS: The target fragments of the exon 39, exon 61 and exon 63 of ATM gene were first amplified using PCR technique, then screened for the SNPs and point mutations using single strand conformation polymorphism (SSCP) technique, finally the representative bands were sequenced for the verification of the new single nucleotide polymorphisms and point mutations using the automatic DNA sequencing technique. RESULTS: Six new SNPs were found in the exon 39, intron 61 and intron 63 of ATM gene. They are respectively the A/T polymorphisms at nucleotide 5689 and 5691 in exon 39, the T/G polymorphisms at nucleotide +69 and +99, the A/G polymorphism at nucleotide +94 in intron 61, the G/C polymorphism at nucleotide +17 in intron 63. Five new point mutations were found in the exon 61, intron 62 and exon 63 of ATM gene. They are respectively the T/G transversion at nucleotide 8618 in exon 61, the T/G transversion at nucleotide -13 in intron 62, the T/G transversion at nucleotide 8793, the G/A transitions at nucleotide 8816 and 8848 in exon 63. The known three SNPs, the G/A polymorphism at nucleotide 5557 in exon 39, the T/C polymorphism at nucleotide +104 in intron 61 and the T/C polymorphism at nucleotide -55 in intron 62, were verified in Chinese of Han ethnicity. CONCLUSION: There are great differences in the SNPs of ATM gene between Chinese of Han ethnicity and Caucasian.

Asian People↗

PubMed2004

Structure of Pseudomonas aeruginosa populations analyzed by single nucleotide polymorphism and pulsed-field gel electrophoresis genotyping.

Pseudomonas aeruginosa has a wide ecological distribution that includes natural habitats and clinical settings. To analyze the population structure and distribution of P. aeruginosa, a collection of 111 isolates of diverse habitats and geographical origin, most of which contained a genome with a different SpeI macrorestriction profile, was typed by restriction fragment length polymorphism based on 14 single nucleotide polymorphisms (SNPs) located at seven conserved loci of the core genome (oriC, oprL, fliC, alkB2, citS, oprI, and ampC). The combination of these SNPs plus the type of fliC present (a or b) allowed the assignment of a genetic fingerprint to each strain, thus providing a simple tool for the discrimination of P. aeruginosa strains. Thirteen of the 91 identified SNP genotypes were found in two or more strains. In several cases, strains sharing their SNP genotype had different SpeI macrorestriction profiles. The highly virulent CHA strain shared its SNP genotype with other strains that had different SpeI genotypes and which had been isolated from nonclinical habitats. The reference strain PAO1 also shared its SNP genotype with other strains that had different SpeI genotypes. The P. aeruginosa chromosome contains a conserved core genome and variable amounts of accessory DNA segments (genomic islands and islets) that can be horizontally transferred among strains. The fact that some SNP genotypes were overrepresented in the P. aeruginosa population studied and that several strains sharing an SNP genotype had different SpeI macrorestriction profiles supports the idea that changes occur at a higher rate in the accessory DNA segments than in the conserved core genome.

Electrophoresis, Gel, Pulsed-Field↗

PubMed2001

An assessment of the utility of single nucleotide polymorphisms (SNPs) for forensic purposes.

This paper assesses the use of single nucleotide polymorphisms (SNPs) for forensic analysis. It demonstrates that relatively small arrays of approx. 50 loci are comparable to existing short tandem repeat (STR) multiplexes. A quantitative test, however, is a prerequisite for mixture interpretation. In addition, as the mixture proportion becomes low, it will be necessary to distinguish between the allele and background. Relatively small biallelic arrays are also suitable to distinguish between closely related individuals such as brothers.

Alleles↗

PubMed2005

Identification of single-nucleotide polymorphisms in the human N-methyl-D-aspartate receptor subunit NR2D gene, GRIN2D, and association study with schizophrenia.

OBJECTIVES: The glutamatergic dysfunction is one of the main hypotheses for the pathophysiology of schizophrenia. N-methyl-D-aspartate receptors are of major interest because phencyclidine, a non-competitive antagonist of N-methyl-D-aspartate receptors, produces a schizophrenia-like psychosis. Therefore, the genes encoding N-methyl-D-aspartate receptor subunits are strong candidates for schizophrenia susceptibility genes. We focused on the N-methyl-D-aspartate receptor subunit NR2D gene in the case-control study of schizophrenia. METHODS: We screened for polymorphisms in exons, exon-intron boundaries and the 5' upstream region of GRIN2D by direct sequencing in 32 Japanese patients. Out of the total 13 single-nucleotide polymorphisms identified, we genotyped 200-201 Japanese patients and 219-221 controls for nine common single-nucleotide polymorphisms (minor allele frequency over 0.05). RESULTS: None of the nine single-nucleotide polymorphisms showed significant differences in genotype and allele frequencies between cases and controls. We observed significant associations of pairwise haplotypes in three combinations of four single-nucleotide polymorphisms, INT10SNP-EX13SNP2, EX13SNP2-EX13SNP3 and EX6SNP-EX13SNP2, with the disease even after the Bonferroni correction (P=1.094 x 10(-6), Pcorrected=2.297 x 10(-5), P=2.825 x 10(-6), Pcorrected=5.933 x 10(-5) and P=2.02 x 10(-4), Pcorrected=4.242 x 10(-3), respectively). The same results were also obtained using the false discovery rate (BL) method at the threshold P value, 2.908 x 10(-3). CONCLUSIONS: We conclude that the GRIN2D locus is a possible genomic region contributing to schizophrenia susceptibility in the Japanese population.

Haplotypes↗

PubMed2000

FHIT gene mutations and single nucleotide polymorphism in Indian oral and cervical squamous cell carcinomas.

Genetic alterations at the FHIT (fragile histidine triad) tumor suppressor gene have been found in various human cancers. We have made an attempt to find point mutations of this gene in two different cancers from India, with entirely different etiologic factors: oral cancer (55 samples) caused by chewing tobacco and cervical cancer (43 samples) caused mainly by HPV (human papilloma virus) infection. Analysis of tumor DNA by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method was performed on each of FHIT exons 5-9 individually, using exon-flanking primers. Two different mutations were identified in both oral and cervical tumors: one at the second nucleotide 3' to the termination codon (TGA) in exon 9 and the other at the ninth nucleotide upstream to the beginning of exon 9. These results indicate that mutations in the FHIT gene are rare events in these tumors in India (approximately 4%). In addition, we found a single nucleotide FHIT gene polymorphism which is due to T/A replacement at 17 nucleotides upstream to exon 9 where the A allele is 0.6 of the population.

Acid Anhydride Hydrolases↗

PubMed2000

A high-density single-nucleotide polymorphism map of Xq25-q28.

A high-density single-nucleotide polymorphism (SNP) map was developed for Xq25-q28 using a targeted approach to SNP discovery. This high-density map includes 217 new SNP markers, and 117 are informative in the CEPH parent population with >20% minor allele frequency. The average distance between SNP markers is 100 kb in the targeted regions. This is the densest genetic map of Xq25-q28 to date. The SNP markers are presented in order by their distance in megabases along the X chromosome, and the markers from the current genetic map are placed using the same scale to produce an integrated map of the region.

Base Sequence↗

PubMed2003

Single nucleotide polymorphism genotyping: biochemistry, protocol, cost and throughput.

The large number of single nucleotide polymorphism (SNP) markers available in the public databases makes studies of association and fine mapping of disease loci very practical. To provide information for researchers who do not follow SNP genotyping technologies but need to use them for their research, we review here recent developments in the fields. We start with a general description of SNP typing protocols and follow this with a summary of current methods for each step of the protocol and point out the unique features and weaknesses of these techniques as well as comparing the cost and throughput structures of the technologies. Finally, we describe some popular techniques and the applications that are suitable for these techniques.

Alleles↗