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At least 145 records · Page 8Linked to original sources

PubMed2002

Three novel single nucleotide polymorphisms in UGT1A10.

Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A10 gene from 24 Japanese patients with various cancers who were administered the anti-tumor drug, irinotecan (CPT-11). The detected SNPs were as follows: 1) SNP, MPJ6_U1A003; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CAGATGCCATGAC/TTTTCAAGGAGAG-3'. 2) SNP, MPJ6_U1A004; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CCTAGAAATAGCC/TTCTGAAATTCTC-3'. 3) SNP, MPJ6_U1A030; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-GGTTGTAGTCATG/ACCAGAGGTGAGT-3' All the three SNPs were located in exon 1 and their frequencies were all 0.021. Among these SNPs, MPJ6_U1A003 and U1A030 resulted in amino acid alterations, T202I and M59I, respectively. The third SNP, MPJ6_U1A004, introduced a synonymous amino acid change (A231A).

Journal Article↗

PubMed2003

Three novel single nucleotide polymorphisms in UGT1A9.

Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A9 gene from 97 Japanese subjects (47 cancer patients and 50 cardiovascular disease patients). The detected SNPs were as follows: 1) SNP, MPJ6_U1A006; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-AATTCTCTTAGGG/TTTCTCAGATGCC-3'. 2) SNP, MPJ6_U1A007; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-TGTTACGGAGTAT/GGATCTCTACAGC-3'. 3) SNP, MPJ6_U1A031; GENE NAME, UGT1A9; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-ACTCATTCTCAGG/AGGGCATGAGGTG-3'. All three SNPs were located in exon 1 with frequencies of 0.036 for MPJ6_U1A006, and 0.005 for MPJ6_U1A007 and MPJ6_U1A031. SNP MPJ6_U1A007 (726T>G) results in formation of a termination codon TAG (Y242X). The other two SNPs, MPJ6_U1A006 (588G>T) and MPJ6_U1A031 (153G>A), result in synonymous changes (G196G and R51R, respectively).

Journal Article↗

PubMed2006

Profiling genetic variation along the androgen biosynthesis and metabolism pathways implicates several single nucleotide polymorphisms and their combinations as prostate cancer risk factors.

Several candidate genes along androgen pathway have been suggested to affect prostate cancer risk but no single gene seems to be overwhelmingly important for a large fraction of the patients. In this study, we first screened for variants in candidate genes and then chose to explore the association between 18 variants and prostate cancer risk by genotyping DNA samples from unselected (n = 847) and familial (n = 121) prostate cancer patients and population controls (n = 923). We identified a novel single nucleotide polymorphism (SNP) in the CYP19A1 gene, T201M, with a mild significant association with prostate cancer [odds ratio (OR), 2.04; 95% confidence interval (95% CI), 1.03-4.03; P = 0.04]. Stratified analysis revealed that this risk was most apparent in patients with organ-confined (T(1)-T(2)) and low-grade (WHO grade 1) tumors (OR, 5.42; 95% CI, 2.33-12.6; P < 0.0001). In contrast, CYP17A1 -34T>C alteration was associated with moderate to poorly differentiated (WHO grade 2-3) organ-confined disease (OR, 1.42; 95% CI, 1.09-1.83; P = 0.007). We also tested a multigenic model of prostate cancer risk by calculating the joint effect of CYP19A1 T201M with five other common SNPs. Individuals carrying both the CYP19A1 and KLK3 -252A>G variant alleles had a significantly increased risk for prostate cancer (OR, 2.87; 95% CI, 1.10-7.49; P = 0.03). In conclusion, our results suggest that several SNPs along the androgen pathway, especially in CYP19A1 and CYP17A1, may influence prostate cancer development and progression. These genes may have different contributions to distinct clinical subsets as well as combinatorial effects in others illustrating that profiling and joint analysis of several genes along each pathway may be needed to understand genetic contributions to prostate cancer etiology.

Aged↗

PubMed2004

[Population genetic analysis of Y-chromosomal single nucleotide polymorphism in six Chinese populations].

OBJECTIVE: To analyze the genetic polymorphism of 15 single nucleotide polymorphism (SNP) loci on the nonrecombining portion of the Y chromosome in 6 populations in China. METHODS: Allelic specific polymerase chain reaction and 2% agarose gel electrophoresis and 6% PAGE were used to analyze the genetic polymorphism of 343 unrelated males, representing 6 populations in China, including Fujian Hans, Sichuan Hans, Mongolian, Hezhen, Sibo and Hui from the South, Northeast and Northwest. RESULTS: Thirty haplogroups were observed, and 3 of them (H15, H16, H18) were seen in all of the six populations. Although the heterozygosity levels of the Hezhen, Mongolian, Sibo populations are similar and those of the other 3 populations (Fujian Hans, Sichuan Hans, Hui) are similar, the pairwise differences among haplogroups are significant. Analysis of molecular variance (AMOVA) and principal component (PC) analysis of the haplogroup distributions suggested highly different allele diversity between group I including Hezhen, Mongolian, Sibo and group II including Hui, Fujian Hans, Sichuan Hans. CONCLUSION: The above analyses show more significant variance components in Northeast/South populations and clearly reveal the geographic genetic relationship among the six populations in the Northeast/Northwest/South. These results confirm the complexity of the genetic structure of Chinese populations and make a significant contribution for constructing the contemporary human gene pool and tracing genetic dispersal trail from Chinese populations.

Alleles↗

PubMed2003

The out of Africa model of varicella-zoster virus evolution: single nucleotide polymorphisms and private alleles distinguish Asian clades from European/North American clades.

Until 1998, varicella-zoster virus (VZV) was generally considered sufficiently stable to allow the use of a single sequenced virus (VZV-Dumas) as a consensual representation of the world VZV genotype. But recent investigations have uncovered a gE mutant virus called VZV-MSP with a second genotype and a distinguishable accelerated cell spread phenotype. A subsequent study suggested that single nucleotide polymorphisms (SNPs) could be applied toward the genetic analysis of the VZV genome. To further assess the scope of genetic variation in the VZV genome on a worldwide basis, we carried out an extensive SNP analysis of structural glycoprotein genes gB, gE, gH, gI, gL, as well as the IE62 regulatory gene in viruses collected from Western Europe, North America and Asia, including the VZV vaccine strain. The SNP data showed segregation of viral isolates of Asian origin from those of Western ancestry into distinct phylogenetic clades. Unexpectedly, however, VZV from Thailand segregated with VZV from Iceland and the United States, i.e. it was more Western than Asian in nature. Further, SNP analysis disclosed strikingly unusual genotypes, e.g. gH genes with up to five missense mutations and gL genes with insertions of an in-frame methionine codon. In summary, these VZV genomic analyses have shown that individual VZV strains, like closely related human beings, have distinctive SNP profiles containing private alleles within just five VZV genes (gB, gH, gE, gL and IE62) that provide a fingerprint to localize ancestry of the viral strain.

Africa↗

PubMed2004

Single nucleotide polymorphism typing on DNA array with hydrophobic surface fabricated by plasma-polymerization technique.

A DNA array has been fabricated on glass substrates, which enables high-throughput analysis of single-base mismatches. In this work, microfabrication-compatible plasma-polymerization (PP) method was used for immobilizing probe DNAs to study the hybridization behavior by changing surface properties. The immobilization matrix consisting of 35 A of PP layer, applied additionally on the streptavidin absorbed hexamethyldisiloxane (HMDS)-PP layer, was constructed on the substrates to anchor biotinylated DNA probes onto the surface. The hydrophobic immobilization matrix was considered to enhance hybridization accuracy and efficiency, compared with its hydrophilic acetonitrile-PP layers. The oligonucleotide arrays fabricated on HMDS-PP surface were shown to be effective in detection of single nucleotide polymorphisms (SNPs) of ApoE gene.

Apolipoproteins E↗

PubMed2005

Recognition of single nucleotide polymorphisms using scanning potential hairpin denaturation.

Conventional single nucleotide polymorphism (SNP) assays, which based their detection on the stringency or temperature of the washing buffers, have encountered difficulties to distinguish a single base pair mismatch from a perfect match. In this study, scanning potential hairpin denaturation (SPHD) has been developed to detect SNP in a sensitive and reliable manner. Combined with hairpin oligonucleotide probes, scanning surface electric potential was used to induce a dissociation of double-stranded DNA around a unique "melting potential" (Vm), and it generated a high-contrast SNP recognition signal. A 21 base pair p53 gene segment was used to test this novel method. A single nucleotide mismatch to the hairpin probes caused an average of 400-800 mV difference in melting potential against the perfect match, while the error of this assay was lower than 20 mV. Experiments demonstrated that the hairpin stem was critical to the method. The concept of scanning potential hairpin denaturation could also be used extensively in different areas of nucleotide hybridization based assays.

DNA↗

PubMed2000

Direct analysis of single-nucleotide polymorphism on double-stranded DNA by pyrosequencing.

Pyrosequencing, a new method for DNA sequencing, is gaining widespread use for many different types of DNA analysis. The method takes advantage of four coupled enzymes in a single tube assay to monitor DNA synthesis in real time using a luminometric detection system. Here, we demonstrate the use of pyrosequencing for direct analysis of single-nucleotide polymorphism on double-stranded PCR product. Pyrosequencing data on the human glutathione peroxidase gene (GPX1) from several individuals were analysed and three different allelic variants were determined and confirmed. The possibility of further simplifying the sequencing and template-preparation steps is discussed.

Alleles↗

PubMed2005

Study of single-nucleotide polymorphisms by means of electrical conductance measurements.

Understanding the complexities of DNA has been a hallmark of science for over a half century, and one of the important topics in DNA research is recognizing the occurrence of mutations in the base-stack. In this article, we present a study of SNPs by direct-contact electrical measurements to a single DNA duplex. We have used short, 11- and 12-bp dsDNA to investigate the change in conductance that occurs if a single base pair, a single base, or two separate bases in the stack are modified. All measurements are carried out in aqueous solution with the DNA chemically bound to the electrodes. These measurements demonstrate that the presence of a single base pair mismatch can be identified by the conductance of the molecule and can cause a change in the conductance of dsDNA by as much as an order of magnitude, depending on the specific details of the double helix and the single nucleotide polymorphism.

DNA↗

PubMed2005

Digital single-nucleotide polymorphism analysis for allelic imbalance.

Digital single-nucleotide polymorphism (SNP) analysis is developed to amplify a single template from a pool of DNA samples, thereby generating the amplicons that are homogeneous in sequence. Different fluorophores are then applied as probes to detect and discriminate different alleles (paternal vs maternal alleles or wild-type vs mutant), which can be readily counted. In this way, digital SNP analysis transforms the exponential and analog signals from conventional polymerase chain reaction (PCR) to linear and digital ones. Digital SNP analysis has the following advantages. First, statistical analysis of the PCR products becomes available as the alleles can be directly counted. Second, this technology is designed to generate PCR products of the same size; therefore, DNA degradation would not be a problem as it commonly occurs when microsatellite markers are used to assess allelic status in clinical samples. Last, digital SNP analysis is designed to amplify a relatively small amount of DNA samples, which is available in some clinical samples. Digital SNP analysis has been applied in quantification of mutant alleles and detection of allelic imbalance in clinical specimens and it represents another example of the power of PCR and provides unprecedented opportunities for molecular genetic analysis.

Allelic Imbalance↗

PubMed2005

Nanocrystal-based bioelectronic coding of single nucleotide polymorphisms.

A bioelectronic method for coding unknown single nucleotide polymorphisms (SNPs) based on the use of different encoding nanocrystals is described. Four such nanocrystals, ZnS, CdS, PbS, and CuS, linked to the adenosine, cytidine, guanosine and thymidine mononucleotides, respectively, are sequentially introduced to the DNA hybrid-coated magnetic-bead solution. Each mutation captures via base pairing different nanocrystal-mononucleotide conjugates, and yields a characteristic multipotential voltammogram, whose peak potentials reflect the identity of the mismatch. The mismatch recognition events are being amplified by the metal accumulation feature of the stripping voltammetric transduction mode. Each of the eight possible one-base mismatches can thus be identified in a single voltammetric run. The use of nanocrystal tracers for detecting two known mutations in a single DNA target is also illustrated in connection to nanocrystals linked to two nucleotides along with a single voltammetric run. The protocol presented should facilitate the rapid, simple, low-cost, and high throughput screening for SNPs.

Base Pair Mismatch↗

PubMed2001

DNA melting analysis for detection of single nucleotide polymorphisms.

BACKGROUND: Several methods for detection of single nucleotide polymorphisms (SNPs; e.g., denaturing gradient gel electrophoresis and denaturing HPLC) are indirectly based on the principle of differential melting of heteroduplex DNA. We present a method for detecting SNPs that is directly based on this principle. METHODS: We used a double-stranded DNA-specific fluorescent dye, SYBR Green I (SYBR) in an efficient system (PE 7700 Sequence Detector) in which DNA melting was controlled and monitored in a 96-well plate format. We measured the decrease in fluorescence intensity that accompanied DNA duplex denaturation, evaluating the effects of fragment length, dye concentration, DNA concentration, and sequence context using four naturally occurring polymorphisms (three SNPs and a single-base deletion/insertion). RESULTS: DNA melting analysis (DM) was used successfully for variant detection, and we also discovered two previously unknown SNPs by this approach. Concentrations of DNA amplicons were readily monitored by SYBR fluorescence, and DNA amplicon concentrations were highly reproducible, with a CV of 2.6%. We readily detected differences in the melting temperature between homoduplex and heteroduplex fragments 15-167 bp in length and differing by only a single nucleotide substitution. CONCLUSIONS: The efficiency and sensitivity of DMA make it highly suitable for the large-scale detection of sequence variants.

Base Pair Mismatch↗

PubMed2006

Capture and release of DNA using aminosilane-modified bacterial magnetic particles for automated detection system of single nucleotide polymorphisms.

Bacterial magnetic particles (BMPs) were modified with 3-[2-(2-aminoethylamino)-ethylamino]-propyltrimethoxysilane (AEEA) to produce a dense amine surface. Modification of BMPs in a toluene solution resulted in an increased amine yield, and approximately 11.3 x 10(4) surface amines were detected on a single particle. The modified BMPs were capable of efficient electrostatic capture of DNA. The maximum amount of DNA captured on 10 microg of aminosilane-modified BMPs was 600 ng. A 10 mM phosphate buffer effectively released the captured DNA. This efficiency was dramatically enhanced by incubation at 80 degrees C and DNA recovery from aminosilane-modified BMPs approached 95%. DNA extraction from whole blood using these modified BMPs, followed by PCR, was successfully performed. Furthermore, automated single nucleotide polymorphism (SNP) detection of the aldehyde dehydrogenase 2 (ALDH2) was demonstrated.

Bacterial Proteins↗

PubMed2002

An electrochemical detection scheme for identification of single nucleotide polymorphisms using hairpin-forming probes.

Single nucleotide polymorphisms are implicated as having a significant role in regulating growth, development and, thereby, human health and disease. We have developed a method for identifying single nucleotide genetic alterations by combining hairpin-forming DNA probes and electrochemical detection of sandwich DNA hybridization. Incorporation of hairpin-forming competitor probes and the catalyzed reporter deposition amplification system further improves assay specificity by 7-fold and sensitivity by 100-fold. We have demonstrated that the system successfully identified the factor V Leiden mutations from human blood specimens.

DNA Probes↗

PubMed2004

No association of the A260G and A386G DAZL single nucleotide polymorphisms with male infertility in a Caucasian population.

BACKGROUND: The human DAZ gene family includes two autosomal genes, BOULE and DAZL, and a Y-chromosomal DAZ gene cluster. All are RNA-binding proteins and assumed to be master regulators of germline gene expression. We have investigated the impact of two DAZL polymorphisms, located at nucleotide positions 260 (SNP 260) and 386 (SNP 386), on the fertility of Caucasian men. These single nucleotide polymorphisms (SNPs) have been described previously to be associated with spermatogenic failure. METHODS: Blood samples were collected and genomic DNA was extracted from 165 normozoospermic men and 202 oligo- or azoospermic patients, of whom 28 displayed an AZFc deletion. The frequencies of A or G allelic variants in SNP 260 and 386 were analysed via TaqMan allelic discrimination assays. In both cases, the A to G transition leads to a threonine to alanine change. RESULTS: A total of 24.2% of the controls showed a heterozygous nucleotide variant (AG) for the SNP 260 and the remaining 75.8% were homozygous for A. In the AZFc-deleted group, this distribution was significantly different, with 39.3% for AG, 57.1% for AA and 3.6% for GG. However, the increased heterozygosity was not correlated with sperm counts and morphology. The patients without deletions displayed a similar allelic pattern to the controls (24.1% AG/75.9% AA). For SNP 386, only the AA nucleotide variant was found in all subjects studied and in no case was the previously described heterozygous AG variant found. CONCLUSION: In a selected Caucasian population, the DAZL SNP 386 is completely absent and SNP 260 is not associated with spermatogenic failure and therefore does not represent a molecular marker for genetic diagnosis of male infertility.

Alanine↗

PubMed2003

Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene.

Point mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population-based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor-tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3' UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ-line. Frequencies of the 500 C-->G and 540 C-->T polymorphisms in the 3' UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor-specific survival was significantly shorter in patients with either the 500 C-->G or 540 C-->T polymorphism than those with wild-type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3' UTR polymorphisms in the CDKN2A gene in tumor invasiveness.

3' Untranslated Regions↗

PubMed2006

Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 vis-à-vis chemotherapy drug cytotoxicity in human glioma.

ERCC1 and ERCC2 have been known to belong to the nucleotide excision repair (NER) pathway and are essential to the repair of cisplatin DNA adducts. In the present study, we have examined the potential correlation of ERCC1, ERCC2 mRNA expression and single nucleotide polymorphism (SNP) to chemotherapy drug cytotoxicity from 49 human gliomas. Fresh human glioma specimens were obtained during surgery. SNPs of ERCC1 and ERCC2 was determined by single strand conformation polymorphism (SSCP) and sequencing. ERCC1 and ERCC2 expression was quantified using real-time quantitative reverse transcription-PCR. Chemotherapy drug cytotoxicity was determined by the tetrazolium (MTT) assay for cisplatin (CDDP), 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), vincristine (VCR) and teniposide (VM26). The results show that there was no statistically significant association between the C8092A polymorphism of ERCC1 or codon 312 and codon 751 polymorphisms of ERCC2 and the chemotherapy drug cytotoxicity. However there was a strong correlation between ERCC1 and ERCC2 mRNA expression levels (Spearman r = 0.42; P < 0.003). Further more, tumor samples with low ERCC1 mRNA expression levels showed enhanced CDDP cytotoxicity (P = 0.0001) while ERCC2 expression was reversely correlated with BCNU cytotoxicity (P = 0.004). In sum, Our results indicated that ERCC1 mRNA expression is associated with CDDP cytotoxicity and ERCC2 mRNA levels is related with BCNU cytotoxicity, while there was no correlation between SNP of ERCC1, ERCC2 and in vitro cytotoxicity of four anticancer drugs, CDDP, BCNU, VCR and VM26.

Adolescent↗

PubMed2003

Single-nucleotide polymorphisms in uncoding regions of ALS2 gene of Japanese patients with autosomal-recessive amyotrophic lateral sclerosis.

ALS2 is an autosomal recessive form of amyotrophic lateral sclerosis (AR-ALS) with juvenile onset, and has been mostly found in North African and Middle Eastern countries. Deletion mutations in the coding exons of a new gene ALS2, encoding a protein with guanine-nucleotide exchange factor (GEF) domains, have recently been identified in ALS2 patients. These mutations are predicted to cause a loss of protein function, indicating that ALS2 is the causative gene underlying ALS2. To examine whether ALS2 is mutated in Japanese ALS patients sharing some characteristics of ALS2, we analyzed ALS2 gene from three patients with AR-ALS. While no deletion mutation was detected in the coding regions of ALS2 gene, several single-nucleotide polymorphisms (SNPs) that have been found in healthy controls as well as in Tunisian ALS2 patients were found mostly in intronic regions of the gene. These results suggest that deletion mutations in ALS2 gene detected in ALS2 patients seem to be uncommon in Japanese AR-ALS, and that SNPs in uncoding regions might possibly be relevant to predisposition to ALS.

Adult↗