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Results for “Single nucleotide polymorphisms”

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PubMed2005

[Association between single-nucleotide polymorphisms in estrogen receptor beta gene and risk of prostate cancer].

OBJECTIVE: This study was undertaken to investigate the relationship of some single nucleotide polymorphisms (SNPs) of estrogen receptor beta (ERbeta) with the risk of prostate cancer (CaP). METHODS: The allele, genotype distribution in an association study with case-control samples involving 40 CaP cases and 86 unrelated healthy male subjects was analyzed. In these individuals, three upstream regions of the proximal ER promoter SNPs (rs3829768, rs1271572, rs3841304) and exon 7 SNP (rs1256049) were analyzed by directly sequencing amplified PCR products of genomic DNA. RESULTS: Four polymorphisms were identified. The rs3841304 was excluded from further analysis because of significant deviation from the Hardy-Weinberg equilibrium. The genotype and allele frequency of rs3829768 (A/G) and rs1271572 (C/A) in the upstream region of proximal promoter were significantly decreased in the CaP cases versus control (P < 0.01). CONCLUSIONS: Our study suggests that this disease of interest is highly associated with rs3829768 (A/G) and rs1271572 (C/A) in CaP cases. CaP, prostate cancer; ERalpha, estrogen receptor alpha; ERbeta, estrogen receptor beta; SNP, Single nucleotide polymorphisms; betaERKO, ERbeta knockout; PIN, prostatic intraepithelial neoplasia; HWE, Hardy-Weinberg equilibrium; NRE, Negative Regulatory Element.

Aged↗

PubMed2000

Analysis of association at single nucleotide polymorphisms in the APOE region.

The discussion of the prospects of using a dense map of single nucleotide polymorphisms (SNPs) to identify disease genes with association analysis has been extensive. However, there is little empiric evidence to support this strategy. To begin to examine the practical issues surrounding this methodology, we identified 10 SNPs in the region immediately surrounding the apolipoprotein E locus (APOE), an established susceptibility gene for Alzheimer disease. Our goal was to examine patterns of allelic association to begin to investigate the question of whether APOE could have been identified using SNPs. Our strongest evidence of association was at the 2 SNPs immediately flanking APOE.

Age of Onset↗

PubMed2002

Screening of single nucleotide polymorphisms in nasopharyngeal carcinoma associated genes by denaturing high-performance liquid chromatography.

OBJECTIVE: To screen single nucleotide polymorphisms (SNPs) of 4 human genes at 6p21.3 by way of denaturing high-performance liquid chromatography (DHPLC). METHOD: Four exons and 1 intron fragments in the PPP1R11, PPP1R10, FLOT1 and KIAA0170 genes at 6p21.3 isolated from the blood samples from 30 patients with nasopharyngeal carcinoma (NPC) and 28 healthy subjects were amplified by PCR, and the products analyzed by DHPLC. Some fragments of interest were sequenced and compared with the sequences available in National Center for Biotechnology Information (NCBI) database. RESULTS: In the 5 fragments, 4 new SNPs were identified and 4 known SNP loci and genotypes were confirmed. CONCLUSION: DHPLC is an effective, economical, and simple method with reliability for SNPs screening.

Adaptor Proteins, Signal Transducing↗

PubMed2002

4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis. Various uses for DNA variations.

At the 4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis (Stockholm, Sweden, 10th-14th October 2001), approximately 100 scientists from more than 20 nations undertook a probing review of latest developments in the field. Despite impressive and still ongoing activities towards SNP discovery and validation, plus efforts towards haplotype exploitation, it was clear that supporting technologies for genotyping are way behind where they need to be. Innate complexity and large variances in aspects of genome function together pose immense challenges that are difficult to surmount in the human situation. In contrast, studies in simpler organisms and population/evolutionary genetics studies are yielding important new insights. Breakthroughs that are being made in understanding the genetic etiology of complex disease tend to involve genes of larger effect or extremely well merited candidates. Linkage studies and proximal phenotypes are being recommended, though the best way forward is still hotly debated. Consequently, many diverse and ambitious projects are underway, from which the data itself will eventually show what is and is not possible.

Genome, Human↗

PubMed2001

Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations.

BACKGROUND: This study was designed to compare genetic differences in single-nucleotide polymorphisms of the S-mephenytoin 4'-hydroxylation (CYP2C19) gene among four Asian populations. METHODS: Polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis of CYP2C19 was conducted in Japanese, Chinese, Thai, and Vietnamese populations. All genotype frequencies were analyzed. Wild-type homozygote and wild-type heterozygote genotypes were extensive proton pump inhibitor (PPI) metabolizers. Mutant-type heterozygote and mutant-type homozygote genotypes were poor PPI metabolizers. RESULTS: No significant differences in CYP2C19 phenotype, calculated based on genotype frequencies, (P > 0.05) were found among the four populations. CONCLUSIONS: Many factors, including CYP2C19 polymorphisms, affect the success rate of Helicobacterpylori eradication with PPI-based therapy. We suspect that CYP2C19 polymorphisms may not be the main factor associated with differences among these four Asian populations in the success rates of H. pylori eradication with PPI-based therapy.

Adolescent↗

PubMed2006

Single-nucleotide polymorphism frequency in a set of selected lines of bread wheat (Triticum aestivum L.).

Information on single-nucleotide polymorphisms (SNPs) in hexaploid bread wheat is still scarce. The goal of this study was to detect SNPs in wheat and examine their frequency. Twenty-six bread wheat lines from different origins worldwide were used. Specific PCR-products were obtained from 21 genes and directly sequenced. SNPs were discovered from the alignment of these sequences. The overall sequence polymorphism observed in this sample appears to be low; 64 single-base polymorphisms were detected in approximately 21.5 kb (i.e., 1 SNP every 335 bp). The level of polymorphism is highly variable among the different genes studied. Fifty percent of the genes studied contained no sequence polymorphism, whereas most SNPs detected were located in only 2 genes. As expected, taking into account a synthetic line created with a wild Triticum tauschii parent increases the level of polymorphism (101 SNPs; 1 SNP every 212 bp). The detected SNPs are available at http://urgi.versailles.inra.fr/GnpSNP">http://urgi.versailles.inra.fr/GnpSNP. Data on linkage disequilibrium (LD) are still preliminary. They showed a significant level of LD in the 2 most polymorphic genes. To conclude, the genome size of hexaploid wheat and its low level of polymorphism complicate SNP discovery in this species.

Bread↗

PubMedDate not supplied

Association between single nucleotide polymorphisms of drug resistance-associated genes and response to chemotherapy in advanced ovarian cancer.

BACKGROUND: Single nucleotide polymorphisms (SNPs) may show clinicopathological importance as prognostic markers. This study examined the association of SNPs and the expression of drug resistance-associated markers with response to chemotherapy in advanced ovarian cancer (stages III and IV) patients. MATERIALS AND METHODS: SNPs were analyzed for MDR1, MRP1, MRP2 and LRP in 60 advanced ovarian cancer patients. The protein expression of each factor was analyzed by immunohistochemistry in all patients. RESULTS: As a result of examining the relevance of SNP genotypes to the response to chemotherapy, a significant relevance (p=0.01) was observed regarding MRP1 exon-17 SNP (G2168A) involving amino acid substitution. No significant relationship was observed between protein expression and the response to chemotherapy or disease-free survival time. CONCLUSION: Analysis of drug resistance gene polymorphism appears to be an indicator of the response to chemotherapy in advanced ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2002

Single-nucleotide polymorphism in repetitive sequences of the human deleted in azoospermia complex.

A simple and inexpensive single-nucleotide polymorphism (SNP) analysis procedure is described that uses the Fotodyne Analyst System equipped with the Gel-Pro Analysis software to compare the relative fluorescent intensity of ethidium bromide stained and MboI restricted amplicons from male individuals. The different intensity ratios reflect the ratio of repetitive elements with and without an MboI restriction enzyme site. The polymerase chain reaction (PCR) products represent a reiterated sequence within the Y-linked deleted in azoospermia (DAZ) complex involved in male fertility in humans. This procedure was utilized to determine the ratio of MboI(+) and MboI(-) repetitive sequences in 32 male individuals from two human populations, the Buryat from Mongolia and the Mayan from Yucatan. The proportion of wildtype to mutant amplicons was found to vary from 0 to 100% among individuals. This technique is well suited for large-scale analysis of the locus investigated in this manuscript and other similar polymorphisms. This approach may contribute to the study of recent human evolution based on Y-chromosome analysis as well as medical and developmental issues concerning the significance of these repetitive elements in male infertility.

Base Sequence↗

PubMed2005

Association of interleukin-10 promoter single nucleotide polymorphisms -819 T/C and -592 A/C with aging.

Increased inflammatory activity is known to accompany aging. Single nucleotide polymorphisms of inflammatory mediator genes might therefore affect the aging process. Relation of eight SNPs (tumor necrosis factor-alpha [TNF-alpha] -1031 T/C, interleukin-10 [IL-10] -819 T/C, IL-1beta -511 C/T, IL-6 -634 C/G, IL-18 -607 A/C, transforming growth factor-beta [TGF-beta] +869 C/T, matrix metalloproteinase-1 [MMP-1] -1607 1G/2G, and MMP-3 -1171 5A/6A) with age or gender was evaluated in 500 Japanese persons (mean age: 56.7 years old, range: 19-100) by the chi-square test. There was a significant association of IL-10 -819 T/C with age (p =.0026). The association remained significant after multivariate logistic regression analysis (odds ratio for an age interval for 1 year, 1.009; 95% CI, 1.002-1.016). Furthermore, the genotype distribution of IL-10 -819 T/C was completely consistent with that of -592 A/C. These data suggest that IL-10 -819 T/C and -592 A/C may be a promising candidate for an aging-related gene in a Japanese population.

Adult↗

PubMed2003

Development and evaluation of an automated workstation for single nucleotide polymorphism discrimination using bacterial magnetic particles.

We designed an automated workstation for magnetic particle-based single nucleotide polymorphism (SNP) discrimination of ALDH genotypes. Bacterial magnetic particles (BMPs) extracted from Magnetospirillum magneticum AMB-1 were used as DNA carriers. The principle for SNP discrimination in this study was based on fluorescence resonance energy transfer (FRET) between FITC (donor) and POPO-3 (acceptor) bound to double-stranded DNA. The workstation is equipped with a 96-way automated pipetter which collects and dispenses fluids as it moves in x- and z-directions. The platform contains a disposable tip rack station, a reagent vessel serving as a stock for POPO-3 and FITC-labeled probes and a reaction station for a 96-well microtiter plate. BMPs were collected by attaching a neodymium iron boron sintered (Nd-Fe-B) magnet on the bottom of the microtiter plate. This system permits the simultaneous heating and magnetic separation of 96 samples per assay. The genotypes ALDH2*1 and ALDH2*2 were discriminated by calculating the relative fluorescence intensities on BMPs.

Aldehyde Dehydrogenase↗

PubMed2003

Effect of secondary structure on single nucleotide polymorphism detection with a porous microarray matrix; implications for probe selection.

Oligonucleotide arrays capable of detecting single nucleotide polymorphisms (SNPs) from amplified nucleic acid have many applications. The expected SNP is usually placed approximately in the center of the probe to ensure the maximum shift in Tm between complementary and SNP sequences. Unfortunately, different short probes (< 30 bases) selected using widely accepted criteria do not perform consistently in this type of assay. Here we present a systematic study on the effect of secondary structure on the ability of oligonucleotide probes to detect an SNP, using real-time array monitoring of a porous microarray substrate that incorporates a novel intra-array mixing system. These results demonstrate that, although positioning of an SNP in the middle of the probe is highly destabilizing, the effect of stable secondary structure on the signal obtained is so dramatic that such probes may be very insensitive. Therefore, if the SNP flanking sequence contains significant secondary structure, then more sensitive probes with good specificity may be obtained by positioning the mutation towards one end of the probe.

Artifacts↗

PubMed2000

Single nucleotide polymorphisms and the future of genetic epidemiology.

In this review, we consider the motivation behind contemporary single nucleotide polymorphism (SNP) initiatives. Many of these initiatives are projected to involve large, population-based surveys. We therefore emphasize the utility of SNPs for genetic epidemiology studies. We start by offering an overview of genetic polymorphism and discuss the historical use of polymorphism in the identification of disease-predisposing genes via meiotic mapping. We next consider some of the unique aspects of SNPs, and their relative advantages and disadvantages in human population-based analyses. In this context, we describe and critique the following six different areas of application for SNP technologies: Gene discovery and mapping. Association-based candidate polymorphism testing. Diagnostics and risk profiling. Prediction of response to environmental stimuli, xenobiotics and diet. Homogeneity testing and epidemiological study design. Physiologic genomics. We focus on key issues within each of these areas in an effort to point out potential problems that might plague the use of SNPs (or other forms of polymorphism) within them. However, we make no claim that our list of considerations are exhaustive. Rather, we believe that they may provide a starting point for further dialog about the ultimate utility of SNP technologies. In addition, although our emphasis is placed on applications of SNPs to the understanding of human phenotypes, we acknowledge that SNP maps and technologies applied to other species (e.g. the mouse genome, pathogen genomes, plant genomes, etc.) are also of tremendous interest.

Alleles↗

PubMed2003

[Single nucleotide polymorphism loci of HIV-1 coreceptor CCR5 gene in Chinese Han people].

OBJECTIVE: To investigate the single nucleotide polymorphism(SNP) loci of HIV-1 coreceptor CCR5 gene in Chinese Han people. METHODS: The coding region of CCR5 was amplified using 2 pairs of primers and the PCR products of all 42 healthy subjects were sequenced by 4 different primers. The results of sequencing were analyzed by DNAstar in search of SNP loci. RESULTS: Six SNP loci were discovered in the coding region of CCR5, among them four SNPs, i.e. 184A-->G, 503G-->T, 688G-->A and 999G-->T, cause amino acids changes and two SNPs are nonsense mutations. One cytosine deletion at the 894nt results in frame shift mutation and prematured termination. 184A-->G, 503G-->T and 999G-->T were found in Chinese Han people for the first time. The allelic frequencies of mutant 184G, 503T and 999T alleles were 1.1%, 21.1% and 10.0% in healthy Hans, respectively. The population distribution of G503T markedly deviated from Hardy-Weinberg equilibrium. CONCLUSION: The SNP loci in the coding region of CCR5 in Chinese Han people has its own characteristics, which is not consistent with those of Japanese and obviously different from those of Caucasian and African.

Adult↗

PubMed2005

Genome-wide linkage analysis for alcohol dependence: a comparison between single-nucleotide polymorphism and microsatellite marker assays.

Both theoretical and applied studies have proven that the utility of single nucleotide polymorphism (SNP) markers in linkage analysis is more powerful and cost-effective than current microsatellite marker assays. Here we performed a whole-genome scan on 115 White, non-Hispanic families segregating for alcohol dependence, using one 10.3-cM microsatellite marker set and two SNP data sets (0.33-cM, 0.78-cM spacing). Two definitions of alcohol dependence (ALDX1 and ALDX2) were used. Our multipoint nonparametric linkage analysis found alcoholism was nominal linked to 12 genomic regions. The linkage peaks obtained by using the microsatellite marker set and the two SNP sets had a high degree of correspondence in general, but the microsatellite marker set was insufficient to detect some nominal linkage peaks. The presence of linkage disequilibrium between markers did not significantly affect the results. Across the entire genome, SNP datasets had a much higher average linkage information content (0.33 cM: 0.93, 0.78 cM: 0.91) than did microsatellite marker set (0.57). The linkage peaks obtained through two SNP datasets were very similar with some minor differences. We conclude that genome-wide linkage analysis by using approximately 5,000 SNP markers evenly distributed across the human genome is sufficient and might be more powerful than current 10-cM microsatellite marker assays.

Alcoholism↗

PubMed2003

Investigating single nucleotide polymorphism (SNP) density in the human genome and its implications for molecular evolution.

We investigated the single nucleotide polymorphism (SNP) density across the human genome and in different genic categories using two SNP databases: Celera's CgsSNP, which includes SNPs identified by comparing genomic sequences, and Celera's RefSNP, which includes SNPs from a variety of sources and is biased toward disease-associated genes. Based on CgsSNP, the average numbers of SNPs per 10 kb was 8.33, 8.44, and 8.09 in the human genome, in intergenic regions, and in genic regions, respectively. In genic regions, the SNP density in intronic, exonic and adjoining untranslated regions was 8.21, 5.28, and 7.51 SNPs per 10 kb, respectively. The pattern of SNP density based on RefSNP was different from that based on CgsSNP, emphasizing its utility for genotype-phenotype association studies but not for most population genetic studies. The number of SNPs per chromosome was correlated with chromosome length, but the density of SNPs estimated by CgsSNP was not significantly correlated with the GC content of the chromosome. Based on CgsSNP, the ratio of nonsense to missense mutations (0.027), the ratio of missense to silent mutations (1.15), and the ratio of non-synonymous to synonymous mutations (1.18) was less than half of that expected in a human protein coding sequence under the neutral mutation theory, reflecting a role for natural selection, especially purifying selection.

DNA, Intergenic↗

PubMedDate not supplied

MDR1 single nucleotide polymorphism C3435T in normal colorectal tissue and colorectal carcinomas detected by MALDI-TOF mass spectrometry.

Single nucleotide polymorphisms (SNPs) may contribute to the malignant process and may show clinicopathological importance as prognostic markers. The multidrug resistance gene MDR1 encodes a membrane transporter which confers cytostatic drug resistance in tumors and protects normal tissues from xenobiotics. We analyzed the C3435T SNP in the MDR1 gene which is associated with altered cellular drug uptake in matched tumor and normal tissues of 45 patients suffering from colorectal carcinoma. We have developed a highly sensitive matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method to survey the C3435T polymorphism in PCR-amplified fragments of the MDR1 gene. Thirteen patients were homozygous for C/C (29%), 15 were heterozygous (33%) and 17 were homozygous for T/T (38%). None of the tumor samples showed an altered SNP compared to their matched normal tissue samples. As analyzed by the Kruskall-Wallis test, none of the clinicopathological parameters was significantly associated with homo- or heterozygosity. The combination of PCR, allele-specific primer extension reactions and MALDI-TOF-MS offers a promising alternative method for genotyping the MDR1 gene especially for heterozygous situations. The inherent advantages of MALDI-TOF-MS based genotyping include its high molecular resolution, high signal-to-noise-ratios and reproducibility, combined with an excellent sensitivity. As none of the tumor samples showed an altered state compared to their matched normal tissue samples, the genotypic frequency of this polymorphism seems not to be altered during colorectal tumorigenesis.

Adult↗

PubMed2006

Characterization and functional investigation of single nucleotide polymorphisms (SNPs) in the human TLR5 gene.

Toll-like receptors recognize pathogen-associated molecular patterns (PAMPs) and TLR5 is the pathogen recognition receptor (PRR) for bacterial flagellin. Patients carrying a R392 stop polymorphism display an inflammatory phenotype and increased susceptibility to pneumonia caused by the flagellated bacteria Legionella pneumophila. While this suggests that TLR5 mutations may be clinically relevant, functional data are not available for the majority of the other TLR5 polymorphisms. We have characterized all known single nucleotide polymorphisms (SNPs) of TLR5 for their functional relevance upon stimulation in transiently transfected CHO-K1 cells. Among the 13 missense SNPs of TLR5 reported in the human genetic databases, three SNPs (c.1174C>T, p.R392X; c.2081A>G, p.D694G; and c.2464C>T, p.L822F) were found to be functionally relevant in transiently transfected CHO-K1 cells. The prevalences of these functionally relevant SNPs in our investigation were 11.9 %, 0 %, and 0 %, in healthy donors. The p.D694G and p.L822F SNPs are of low frequency in the Caucasian population though further investigations of the common p.R392X variant alone or of functional relevant TLR5 SNPs in combination with other TLR SNPs will elucidate their possible role on disease susceptibility in humans and may facilitate clinical diagnosis.

Alleles↗

PubMed2005

[Association of single nucleotide polymorphism in matrix metalloproteinases promoter with susceptibility to ovarian cancer].

OBJECTIVE: To investigate the association of single nucleotide polymorphism in matrix metalloproteinase (MMP)-1 and MMP-3 promoter with susceptibility to ovarian cancer. METHODS: The genotype of MMP-1 and MMP-3 gene promoter region was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 ovarian cancer patients (ovarian cancer group) and 151 unrelated healthy women (control group). RESULTS: The frequencies of 2G and 1G alleles in ovarian cancer group were 68.0%, 32.0% and in control group 66.9%, 33.1%, with no significant difference between the two groups (P > 0.05); the genotype frequencies of 1G/1G, 1G/2G, 2G/2G in ovarian cancer group (16.4%, 31.1% and 52.5%) was not significantly different from that in control group (16.6%, 33.1% and 50.3%) (P > 0.05). Compared to 1G/1G genotype, neither 2G/2G nor in combination with 1G/2G genotype significantly modified the risk of developing ovarian cancer. The adjusted odds ratio was 1.05 (95% CI = 0.53-2.07) and 1.00 (95% CI = 0.52-1.90), respectively. The frequencies of 5A and 6A alleles in MMP-3 in ovarian cancer group were 17.2%, 82.8% and in control group 20.2%, 79.8%, with no significant difference between the two groups (P > 0.05). No significant difference in genotype (5A/5A, 5A/6A and 6A/6A) distribution between ovarian cancer and control groups was observed, either. Compared to 6A/6A genotype, 5A/5A plus 5A/6A genotype did not significantly modify the risk of developing ovarian cancer, the adjusted odds ratio was 1.34 (95% CI = 0.81-2.23). 2G allele of MMP-1 and 6A allele of MMP-3 were in linkage disequilibrium (chi(2) = 56.53, P < 0.01). CONCLUSION: MMP-1 and MMP-3 promoter polymorphism is not associated with the susceptibility to ovarian cancer.

Case-Control Studies↗