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Results for “single nucleotide polymorphisms”

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At least 919 records · Page 51Linked to original sources
PubMed2005

[Investigation of single nucleotide polymorphisms in the promoter region of mannan-binding lectin gene in Bais, Uars and Lahus ethnics from China].

AIM: To investigate the single nucleotide polymorphisms(SNP) in the promoter region of mannan-binding lectin (MBL) gene in Bais, Uars and Lahus ethnics. METHODS: 71, 73 and 94 blood samples were obtained from Bais, Uars and Lahus subjects, respectively from Yunnan province. Genomic DNA was isolated from leucocytes. Polymorphism alleles -550(G/C, named H/L alleles), -220(G/C, X/Y alleles) and +4(C/T, P/Q alleles) in the promoter region of MBL gene were detected by sequence-specific primer-PCR and molecular beacon real-time PCR, and the frequencies of haplotypes and genotypes were analyzed. RESULTS: The frequencies of genotypes in Bais, Uars and Lahus ethnics were as follows: LYP/LYP 4(5.6%), 4(5.5%)and 2(2.1%); HYP/LYQ 6(8.5%), 11(15.1%) and 12(12.8%); LYP/LYQ 21(29.6%), 14(19.2%) and 51(54.3%); LXP/LXP 1(1.4%), 2(2.7%)and 0,LYQ/LYQ 10(14.1%); 14(19.2%), 7(7.4%), LXP/LYQ 10(14.1%), 13(17.8%) and 15(16.0%); HYP/LYP 4(5.6%), 3(4.1%) and 4(4.3%); HYP/LXP 3(4.2%), 1(1.4%) and 0; HYP/HYP 12(16.9%), 11(15.1%) and 3(3.2%). CONCLUSION: The distribution of alleles L/H is statistically different among Uars, Bais and Larhus(P<0.01), while X/Y and P/Q are not statistically significant(P>0.05). All studied haplotypes and genotypes are statistically different among the 3 ethnics(P<0.01). Genotypes LYP/LYQ and LXP/LYQ are common in all the 3 ethnics.

Asian People↗
PubMed1999

Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene and breast cancer susceptibility.

In order to evaluate the role of inherited variation in the estrogen receptor (ESR1) gene in human breast cancer, we determined intronic sequences flanking each ESRI exon; identified multiple SNPs and length polymorphisms in the ESR1 coding sequence, splice junctions and regulatory regions; and genotyped families at high risk of breast cancer and population-based breast cancer patients and controls. Of 10 polymorphic sites in ESR1, four are synonymous SNPs, two are nonsynonymous SNPs and four are length polymorphisms; five are novel. No ESR1 polymorphisms were associated with breast cancer, either in the high-risk families or the case-control study. We therefore conclude that inherited genetic variation is not a mechanism by which the estrogen receptor is commonly involved in breast cancer development.

5' Untranslated Regions↗
PubMed2003

Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1.

CYP1A2 polymorphism has been well studied in white persons and Asians but not in Africans. We performed CYP1A2 genotype and phenotype analysis using caffeine in Ethiopians living in Ethiopia (n = 100) or in Sweden (n = 73). We sequenced the CYP1A2 gene using genomic DNA from 12 subjects, which revealed a novel intron 1 single-nucleotide polymorphism (SNP), -730C>T. We developed SNP-specific polymerase chain reaction-restriction fragment length polymorphism genotyping and molecular haplotyping methods for the intron 1 SNPs, and four different haplotypes were identified: CYP1A2*1A (wild-type for all SNPs), CYP1A2*1F (-164A), CYP1A2*1J (-740G and -164A), and CYP1A2*1K (-730T, -740G, and -164A), having frequencies of 39.9, 49.6, 7.5, and 3.0%, respectively. The frequency of CYP1A2*1J and CYP1A2*1K among Saudi Arabians (n = 136) was 5.9% and 3.6%, and among Spaniards (n = 117) 1.3% and 0.5%, respectively. Functional significance of the different intron 1 haplotypes was analyzed. Subjects with CYP1A2*1K had significantly decreased CYP1A2 activity in vivo, and reporter constructs with this haplotype had significantly less inducibility with 2,3,7,8-tetrachlorodibenzo-p-dioxin in human B16A2 hepatoma cells. Electrophoretic mobility shift assay using nuclear extracts from B16A2 cells revealed a specific DNA binding protein complex to an Ets element. Efficient competition was obtained using oligonucleotide probes carrying the wt sequence and Ets consensus probe, whereas competition was abolished using probes with the -730C>T SNP alone or in combination with -740T>G (CYP1A2*1K). The results indicate a novel polymorphism in intron 1 of importance for Ets-dependent CYP1A2 expression in vivo and inducibility of the enzyme, which might be of critical importance for determination of interindividual differences in drug metabolism and sensitivity to carcinogens activated by CYP1A2.

Adult↗
PubMed2006

The association of single nucleotide polymorphisms in the 5'-regulatory region of the lumican gene with susceptibility to high myopia in Taiwan.

PURPOSE: To study the relationships between single nucleotide polymorphisms (SNPs) of lumican, decorin, and DSPG3 genes and high myopia. METHODS: One hundred and twenty adult patients with high myopia (< -10.0 D) and 137 controls were used to study the relationships between the decorin, lumican, and DSPG genes and high myopia. All subjects were free of ocular diseases, other than myopia, as well as of other systemic genetic diseases. Genotyping was performed by direct sequencing after PCR amplification of chromosomal DNA. Allele frequencies were tested for Hardy-Weinberg disequilibrium. The chi(2) or Fisher test was conducted to investigate the genotypic and allelic distribution between the high myopia and control groups. RESULTS: The genotyping success rate was 100%. Univariate analysis revealed significant differences between patients and control subjects with respect to one of the SNPs (rs3759223, C->T) of the lumican gene, with a p value of 0.000283. There was no significant relationship between other SNPs of lumican, decorin, and DSPG genes and high myopia. CONCLUSIONS: Our results indicate that an SNP (rs3759223), which is located in the promoter region of the lumican gene, may be worth further investigation to determine its association with development of high myopia.

5' Flanking Region↗
PubMed2006

Association of the methylenetetrahydrofolate reductase A1298C but not the C677T single nucleotide polymorphism with sickle cell disease in Bahrain.

The association of methylenetetrahydrofolate reductase (MTHFR) gene mutations, C677T and A1298C, together with changes in homocysteine (Hcy) levels was investigated in 106 sickle cell disease patients and 156 healthy controls from Bahrain. The mutation analysis was done by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). While the frequencies of the mutant alleles C677T and A1298C were comparable between patients and controls, the frequency of the A1298C (C/C) (p = 0.03) but not C677T (T/T) (p = 0.67) genotype, and of the 677T/1298C haplotype were significantly higher in the patients (p = 0.05). Homocysteine levels were normal in all subjects. This suggests that the A1298C, but not C677T, mutation is associated with the genotype of sickle cell disease.

Adolescent↗
PubMed2001

Amplified single-nucleotide polymorphisms and a (GA)(n) microsatellite marker reveal genetic differentiation between populations of Histoplasma capsulatum from the Americas.

Histoplasma capsulatum has a worldwide distribution but is particularly concentrated in the midwestern United States and throughout Central and South America. Genetic differences between isolates resident in separate parts of the world have been reported, but the relationship between the isolates and the level of migration between different endemic foci has not been clear. In this study we used multilocus genotypes based on amplified polymorphic loci and one microsatellite to quantify the level of genetic differentiation occurring between North and South American populations of H. capsulatum. Significant genetic differentiation occurred between isolates obtained from Indiana and Alabama, and a marked division was seen between the Indiana population and the Class 1 isolates from St. Louis. Strong genetic differentiation occurred between the two North American populations and the Colombian population. This study supports the separation of North and South American H. capsulatum into different species, which has been proposed under the phylogenetic species concept.

Genetic Markers↗
PubMed2006

Single nucleotide polymorphisms of the TGFB1 gene and lung cancer risk in a Korean population.

The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the transforming growth factor-beta 1 (TGFB1) gene and susceptibility to lung cancer and the clinical effect of the SNPs on lung cancer progression in a Korean population. Two polymorphisms in the promoter region of the TGFB1 (T-1572C, C-509T), and one SNP in codon 10 (T+869C) were determined using a SNaPshot primer extension assay in 194 Korean lung cancer patients and 283 normal controls. The polymorphic allele frequencies of A-1572G, C-509T, and T+869C were similar among lung cancer patients (0.52, 0.47, and 0.47, respectively) and controls (0.54, 0.46, and 0.44, respectively). When the data was stratified for smoking history, patients who smoked heavily and had heterozygous C-509T and T+869C genotypes showed an increased lung cancer risk (odds ratio OR = 3.77, confidence interval 95% CI = 1.25-11.30, P = 0.017; OR = 3.61, 95% CI = 1.21-10.74, P = 0.021 for each), after adjustment for age and sex. When heterozygous and homozygous variants for each SNPs were analyzed together, patients who were smokers and had variant genotypes also showed increased risk compared to the reference group. Further analyses to test the effect of the SNPs on the clinical parameters did not reveal an association of each polymorphic allele to the tumor stage or response to treatment. In addition, DNA fragments containing polymorphic genotype of the promoter region (-509T) showed increased transcriptional activity in luciferase assays using non-small cell lung cancer cell lines. In conclusion, this study suggests that heavy smokers in this Korean population who have specific polymorphic variants, which have been associated with increased transcriptional activity of TGFB1, might be more vulnerable to lung cancer.

Base Sequence↗
PubMed2005

[Possible association between 278C/A single nucleotide polymorphism of FKBP6 and idiopathic azoospermia].

OBJECTIVE: To investigate 2 polymorphism sites in exon 3 and intron 2 of FKBP6 in Chinese population, while screening the gene mutations and polymorphisms in exons 3, 4 of FKBP6, and the association of these polymorphisms with azoospermia. METHODS: Possible variations of exons 3, 4 and genotypes and frequencies of 2 polymorphic loci were examined by denaturing high-performance liquid chromatography(DHPLC) and PCR-restriction fragment length polymorphism(PCR-RFLP) technique in 177 azoospermia patients and 231 control individuals. RESULTS: The observed allele frequencies conformed well to Hardy-Weinberg equilibrium. The frequency of 278A allele was significantly higher in controls than that in patients (P<0.05). C/T(s7797242) polymorphism was not found in either group and variations in exons 3, 4 were not detected. CONCLUSION: 278A polymorphism of FKBP6 gene was associated with idiopathic azoospermia, while C/T, 370G/A, 430G/C, 467T/C, 468G/A polymorphisms might be very rare in Chinese population.

Azoospermia↗
PubMed2004

Fourteen novel single nucleotide polymorphisms in the SLC22A2 gene encoding human organic cation transporter (OCT2).

Thirty-three genetic variations including fourteen novel ones were found in the SLC22A2 gene from 116 Japanese individuals. The novel variations were as follows: 596C>T (MPJ6_OC2003), 602C>T (MPJ6_OC2004), IVS5+20A>G (MPJ6_OC2010), IVS5-84_-83insG (MPJ6_OC2013), IVS6+30T>C (MPJ6_OC2014), IVS6+146G>T (MPJ6_OC2016), IVS6+179G>T (MPJ6_OC2017), IVS6-16delT (MPJ6_OC2018), 1920G>A (MPJ6_OC2022), 2153G>A (MPJ6_OC2026), 2157C>T (MPJ6_OC2028), 2306T>C (MPJ6_OC2031), 2342+5T>C (the last nucleotide number of mRNA+the position in the 3'-flanking region; MPJ6_OC2032) and 2342+127T>C (MPJ6_OC2033). Six variations were located in the exons, four of which were in the 3'-untranslated region (3'-UTR) of exon 11; six were in the introns; and two were in the 3'-flanking region. The frequencies were 0.802 for IVS5-84_-83insG, 0.013 for 602C>T, 0.009 for 596C>T, and 0.004 for the other 11 variations. Among them, 596C>T and 602C>T resulted in amino acid substitutions (Thr199Ile and Thr201Met, respectively).

Amino Acid Substitution↗
PubMed2005

Allelic imbalance analysis of oral tongue squamous cell carcinoma by high-density single nucleotide polymorphism arrays using whole-genome amplified DNA.

Multiple displacement-based whole-genome DNA amplification is a promising tool to obtain sufficient DNA from small tissue specimens for various genetic analyses, such as SNP array-based analysis. Using Affymetrix 10 K and 100 K SNP mapping array, we evaluated the performance of the Phi29 DNA polymerase-based genome amplification. Greater than 99% concordance in genotyping calls were achieved between amplified and non-amplified DNAs for both arrays. By utilizing the Affymetrix GeneChip Chromosome Copy Number Tool, the allelic imbalance profiles for the advanced stage oral tongue squamous cell carcinoma (OTSCC) were generated based on 10 K and 100 K SNP mapping array results. The results from these two array platforms agree closely, but more precise allelic imbalance patterns can be revealed from the 100 K SNP mapping array data. Furthermore, our data suggested a frequent loss at 3p11-p12 for advanced stage OTSCC.

Allelic Imbalance↗
PubMed2005

A possible association between the -116C/G single nucleotide polymorphism of the XBP1 gene and lithium prophylaxis in bipolar disorder.

Bipolar disorder (BPD) is a severe, chronic, and life-threatening illness, and its pathogenesis remains unclear. Recently, a functional polymorphism (-116C/G) of the X-box binding protein 1 (XBP1) gene was reported to be a genetic risk factor for BPD. Moreover, the endoplasmic reticulum stress responses were impaired in cultured lymphocytes from BPD patients with the -116G allele and only valproate rescued such impairment among three major mood stabilizers. In this context, we hypothesized that BPD patients with different genotypes respond differently to mood stabilizers. We investigated the association between the -116C/G polymorphism of the XBP1 gene and lithium response in Japanese patients with BPD. We found that lithium treatment is more effective among BPD patients with the -116C allele carrier than in patients homozygous for the -116G allele. The association between the -116C/G polymorphism and clinical efficacy of mood stabilizers should be further investigated in a prospective study with a larger sample.

Adult↗
PubMed2006

Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients.

The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123 patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85-3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85-16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5-8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might be more prominent in men.

Arthritis, Rheumatoid↗
PubMed2006

Identification of single nucleotide polymorphism of adipocyte fatty acid-binding protein gene and its association with fatness traits in the chicken.

Fatty acid-binding proteins (FABP) belong to a superfamily of lipid binding proteins that exhibit a high affinity for long chain fatty acids and appear to function in metabolism and intracellular transportation of lipids. The current study was designed to investigate the effects of the adipocyte (A)-FABP gene on chicken growth and body composition traits. Two F2 resource populations were used in the current study. Body weight and body composition traits were measured in the populations. Primers for the coding region of the A-FABP gene were designed from chicken genomic and cDNA sequences. Polymorphism between parental lines was detected by DNA sequencing, and the PCR-RFLP method was developed to genotype the F2 populations. The results indicated that an A-FABP gene polymorphism was associated with abdominal fat weight and percentage of abdominal fat, and the A-FABP gene could be a candidate locus or linked to a major gene(s) that affects abdominal fat content in the chicken.

Animals↗
PubMed2005

Linkage between I172N mutation, a marker of 21-hydroxylase deficiency, and a single nucleotide polymorphism in Int6 of CYP21B gene: a genetic study of Sardinian family.

Congenital adrenal hyperplasia (CAH) is a genetic disorder due to 21-hydroxylase deficiency. More than 90% of CAH cases are caused by mutations of CYP21B gene, most of which are the result of microconversion events between the functional gene and its pseudogene. Using a combination of RFLP and direct sequencing analysis, in this paper we describe the genetic study of a Sardinian family carrying I172N mutation in linkage with a SNP namely 1636 Int6. The characterization of new polymorphisms in CYP21B can improve the analysis of segregation of CYP21B mutated alleles especially in genetic familial studies. The analysis of linkage between specific mutations and this SNPs, especially if focused on genetic familial studies, may improve the quality of genetic analysis of 21-hydroxylase deficiency.

17-alpha-Hydroxyprogesterone↗
PubMed2005

G125A single-nucleotide polymorphism in the human BAX promoter affects gene expression.

Earlier we had reported a guanine to adenosine substitution at position 125 (G125A) in the BAX promoter, and its association with higher stage of the disease and failure to achieve complete response to treatment in chronic lymphocytic leukemia (CLL) patients. The aim of this study was to test the hypothesis that G125A leads to a reduction in the transcription of the BAX gene and that this is a direct cause of altered BAX mRNA and protein expression. In lymphocytes of CLL patients, BAX mRNA expression was determined by RNase protection assay and Bax protein was detected by immunoblotting. The presence of G125A in the BAX promoter was associated with lower BAX mRNA (P=0.004) and protein (P=0.024) levels. In transient expression assays using wild-type and mutant BAX promoter sequences linked to Luciferase as a reporter, the G125A polymorphism reduced expression of the BAX promoter by 2.6-fold. These studies suggest a mechanism for the biological effect of the G125A.

Adenine↗
PubMed2005

Single nucleotide polymorphisms in the apoptosis receptor gene TNFRSF6.

The homotrimeric Fas receptor, an inducer of lymphocyte apoptosis, plays a critical role in cellular pathways of immune homeostasis and immunologic tolerance. Inherited and acquired defects in the Fas gene, TNFRSF6 (tumor necrosis factor receptor superfamily member 6) have been associated with human autoimmune lymphoproliferative syndrome (ALPS) and a spectrum of other complex autoimmune diseases and malignancies. In addition to over 60 deleterious mutations associated with dominant inhibitory defects or null mutations of TNFRSF6, several sequence variants have been noted. To facilitate interpretation of genotypes of this important locus, we sequenced DNA from unrelated, healthy Caucasians and African Americans. Two new and 12 previously recorded SNPs were confirmed, and their allele frequencies were determined. We also investigated haplotype frequencies and linkage disequilibrium (LD) coefficients for these SNPs in Caucasians. Four TNFRSF6 SNP pairs were found to be in strong LD. The TNRFSF6 SNPs are useful for linkage and loss of heterozygosity studies probing the role of Fas-mediated apoptosis in autoimmune diseases and malignancies.

Black or African American↗
PubMed2006

The investigation of mutation and single nucleotide polymorphism of receptor tyrosine kinases and downstream scaffold molecules in acute myeloid leukemia.

We investigate the role of mutations of receptor tyrosine kinases as well as their downstream scaffold molecules in leukemogenesis of acute myeloid leukemia (AML) in Chinese patients. Genes of interest included FLT3, PDGFRbeta, KDR, CSF2Rbeta, SOCS1, PIAS3 and SHIP. The coding sequence of these genes was analysed by the reverse transcription-polymerase chain reaction to search novel mutations. A novel mutation (A > T, Q1154L) of SHIP (1 of 192, 0.52%) was identified and another novel mutation (C > T, R685C) of PDGFRbeta (2 of 192, 1.04%). In addition, FLT3 mutations were seen in three of five patients with AML following myelodysplastic syndrome (60%) and 39 of 268 (14.6%) de novo AML patients (P < 0.05). No mutations were found in the coding sequence regions of KDR, CSF2Rbeta, SOCS1 or PIAS3.

Base Sequence↗
PubMed2006

Detection of C:C mismatch base pair by fluorescence spectral change upon addition of silver (I) cation: toward the efficient analyses of single nucleotide polymorphism.

We have already found that silver (I) cation specifically binds to C:C mismatch base pair in heteroduplex, which increases the melting temperature of heteroduplex involving C:C mismatch base pair by about 4 degrees C. This result shows that addition of the metal cation is a promising strategy for the mismatch base pair detection in heteroduplex, but UV melting to determine the melting temperature is time-consuming. In the present study, to develop a more convenient way for the mismatch base pair detection, we examined the fluorescence spectral change of fluorescent-labelled duplex upon addition of the metal cation. Addition of silver (I) cation to the heteroduplex involving the C:C mismatch base pair significantly changed the fluorescence intensity, but no significant change in the fluorescence intensity was observed for the duplexes involving other base pairs. Our results certainly support the idea that the fluorescence spectral change upon the addition of the metal cation could be a convenient strategy for the mismatch base pair detection by the heteroduplex analysis, and may eventually lead to progress in SNP genotyping.

Base Pair Mismatch↗