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At least 289 records · Page 16Linked to original sources
PubMed2006

SNP-RFLPing: restriction enzyme mining for SNPs in genomes.

BACKGROUND: The restriction fragment length polymorphism (RFLP) is a common laboratory method for the genotyping of single nucleotide polymorphisms (SNPs). Here, we describe a web-based software, named SNP-RFLPing, which provides the restriction enzyme for RFLP assays on a batch of SNPs and genes from the human, rat, and mouse genomes. RESULTS: Three user-friendly inputs are included: 1) NCBI dbSNP "rs" or "ss" IDs; 2) NCBI Entrez gene ID and HUGO gene name; 3) any formats of SNP-in-sequence, are allowed to perform the SNP-RFLPing assay. These inputs are auto-programmed to SNP-containing sequences and their complementary sequences for the selection of restriction enzymes. All SNPs with available RFLP restriction enzymes of each input genes are provided even if many SNPs exist. The SNP-RFLPing analysis provides the SNP contig position, heterozygosity, function, protein residue, and amino acid position for cSNPs, as well as commercial and non-commercial restriction enzymes. CONCLUSION: This web-based software solves the input format problems in similar softwares and greatly simplifies the procedure for providing the RFLP enzyme. Mixed free forms of input data are friendly to users who perform the SNP-RFLPing assay. SNP-RFLPing offers a time-saving application for association studies in personalized medicine and is freely available at http://bio.kuas.edu.tw/snp-rflp/.

Animals↗
PubMed2026

Prenatal SNP-array chromosomal microarray analysis in 3,549 pregnancies: indication-specific yields and clinical implications.

BACKGROUND: SNP-based chromosomal microarray analysis (CMA) is widely used in invasive prenatal diagnosis, yet real-world performance across contemporary referral pathways, especially in the NIPT era, remains incompletely characterized. METHODS: We retrospectively analyzed 3,549 prenatal invasive samples tested by SNP array, and evaluated diagnostic yield overall and by referral indication and ultrasound phenotype. RESULTS: In total, we identified 398 pathogenic or likely pathogenic (P/LP) variants across 386 fetuses, resulting in an overall diagnostic yield of 10.9% (386/3,549). These findings comprised 223 aneuploidies and 175 pathogenic CNVs. In contrast, variants of uncertain significance (VOUS) were detected in 12.0% (426/3,549) of cases. Diagnostic yields were heavily stratified by indication: yields peaked in NIPT high-risk referrals (38.9%) and were intermediate in ultrasound-based cases (~ 11%), but dropped significantly in the advanced maternal age (AMA; 4.2%) and serum screening (~ 5-6%) groups. Conversely, VOUS rates remained remarkably stable across all referral categories. Sub-analysis of ultrasound abnormalities revealed that multisystem anomalies conferred the highest risk (27.3%), driven predominantly by aneuploidies; among soft markers, increased nuchal translucency (NT) emerged as the strongest predictor of chromosomal pathology. CONCLUSIONS: In our cohort, SNP-array identified clinically actionable findings in 10.9% of cases. NIPT enriched diagnostic yields, particularly for aneuploidies, and NT thickness was strongly associated with pathogenic findings. These results support an indication-based approach to genomic testing, with NIPT as a triage tool for aneuploidy and CMA for high-risk populations, while improving VOUS counseling.

Humans↗
PubMed2006

[SNP markers: methods of analysis, ways of development, and comparison on an example of common wheat].

SNPs (single nucleotide polymorphisms), which belong to the last-generation molecular markers, occur at high frequencies in both animal and plant genomes. The development of SNP markers allows to automatize and enhance tenfolds the effectiveness of genotype analysis. This review summarizes literature data on methods of SNP polymorphism analysis. Various methods of developing SNP markers are considered, taking common wheat Triticum aestivum L. as an example. These markers are compared to other DNA markers, in order to ensure adequate choice of marker type for solving various molecular genetic problems.

DNA, Plant↗
PubMed2007

Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects the KLF6 gene.

A genome-wide association analysis using the Affymetrix 100K SNP array was carried out in a case-control study of lung cancer. Allele frequencies were estimated initially in DNA pools. Significant differences in allele frequency detected in the SNP array analysis were first tested in the same DNA pools by pyrosequencing and then by individual genotyping. DNA pooling analysis identified rs10508266 SNP, located approximately 12.5kb from the 5'-end of the KLF6 gene, as a marker showing significant association with lung cancer risk. Since the SNP was in significant linkage disequilibrium with the KLF6 gene region, we analyzed an Italian population of 338 lung adenocarcinoma cases and 335 controls for the possible role of the reported functional rs3750861 SNP, located 15.6kb from the rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of 265 non small cell lung cancer cases, and 356 controls, however, did not confirm the association. In light of the reported functional involvement of the KLF6 gene in lung cancer and in other cancer types and to the functional nature of the rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk, although additional studies in large series are needed to confirm our findings and to elucidate the mechanism by which the KLF6 SNPs influence lung cancer risk.

Adenocarcinoma↗
PubMed2003

Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis.

Most human cancers are characterized by genomic instability, the accumulation of multiple genetic alterations, and allelic imbalance throughout the genome. Loss of heterozygosity (LOH) is a common form of allelic imbalance, and the detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. Global patterns of LOH can be discerned by allelotyping of tumors with polymorphic genetic markers. Microsatellites are reliable genetic markers for studying LOH, but typically only a modest number of microsatellites are tested in LOH studies because the genotyping procedure can be laborious. Here we describe the use of a new alternative approach to comprehensive allelotyping in which samples are genotyped for nearly 1500 single-nucleotide polymorphism (SNP) loci distributed across all human autosomal arms. We examined the pattern of allelic imbalance in human transitional cell carcinomas of the urinary bladder including 36 primary tumors and 1 recurrent tumor with matched normal DNAs. The call rate for all SNPs was 78.5 +/- 1.87% overall samples. Overall, the median number of allelic imbalance was 47.5, ranging from 20 to 118. The mean number of allelic imbalances was 36.58, 51.30, and 67.78 for pT(a), pT(1), and > or =pT(2), respectively, and also increased by grade. The SNP microarray analysis result was validated by comparison with microsatellite allelotype analysis of 118 markers in the same tumors. Overall, the two methods produced consistent loss patterns at informative loci. The SNP assay discovered previously undiscovered allelic imbalances at chromosomal arms 12q, 16p, 1p, and 2q. The detection of LOH and other chromosomal changes using large numbers of SNP markers should enable rapid and accurate identification of allelic imbalance patterns that will facilitate the mapping and identification of important cancer genes. Moreover, SNP analysis raises the possibility of individual tumor genome-wide allelotyping with potential prognostic and diagnostic applications.

Carcinoma, Transitional Cell↗
PubMed2006

Potential regulatory SNPs in promoters of human genes: a systematic approach.

Single nucleotide polymorphisms (SNPs) can significantly contribute to the cellular level of the mRNA transcripts encoded by human disease related genes. DNA variations between individuals can be an indication of predisposition to disease or affect the response to treatment. An algorithm allowing in silico extraction of SNPs with the high probability of influencing the level of gene expression is highly desirable. We performed a whole-genome analysis of SNP markers in regulatory areas of the human genes. Computational criteria were applied to predict an influence of the nucleotide replacement on the individual gene's expression. We formed a list of 14127 regulatory SNPs corresponding to 8555 regulatory areas suitable for future association studies. A catalogue of 1859 SNP entries, confirmed by analysis in populations, and allocated to 1607 human regulatory areas was created. We also revealed 13 cases of overlapped promoters corresponding to the human genes transcribed from opposite DNA strands and containing the regulatory SNP markers validated in populations. A population-validated set of regulatory SNP markers is organized in a database available in open access as a Supplementary file and by ftp://194.67.85.195/.

Base Sequence↗
PubMed2005

SNPLINK: multipoint linkage analysis of densely distributed SNP data incorporating automated linkage disequilibrium removal.

SUMMARY: SNPLINK is a Perl script that performs full genome linkage analysis of high-density single nucleotide polymorphism (SNP) marker sets. The presence of linkage disequilibrium (LD) between closely spaced SNP markers can falsely inflate linkage statistics. SNPLINK removes LD from the marker sets in an automated fashion before carrying out linkage analysis. SNPLINK can compute both parametric and non-parametric statistics, utilizing the freely available Allegro and Merlin software. Graphical outputs of whole genome multipoint linkage statistics are provided allowing comparison of results before and after the removal of LD.

Algorithms↗
PubMed2005

The KPNA3 gene may be a susceptibility candidate for schizophrenia.

The present study investigated the possible association of the KPNA3 locus in the 13q14 region with schizophrenia. We detected 7 single nucleotide polymorphisms (SNPs) on 13q14, one (rs6313) present at the HTR2A locus and the other 6 at the KPNA3 locus, among 124 British family trios consisting of mother, father and affected offspring with schizophrenia. The transmission disequilibrium test (TDT) showed allelic association for rs3736830 (chi(2)=8.66, P=0.003), rs2181185 (chi(2)=3.86, P=0.049) and rs626716 (chi(2)=5.82, P=0.016), but not for rs6313 (chi(2)=0.009, P=0.926). The global P-value was 0.029 for 1000 permutations with the TDT. The 2-SNP haplotype analysis showed a disease association for the rs2273816-rs3736830 haplotypes (chi(2)=7.63, d.f.=2, P=0.022), the rs3736830-rs2181185 haplotypes (chi(2)=10.30, d.f.=2, P=0.006) and the rs2181185-rs3782929 haplotypes (chi(2)=9.26, d.f.=2, P=0.01). The global P-value was 0.034 for 1000 permutations with the 2-SNP haplotype analysis. The 6-SNP haplotype system also showed a weak association with the illness (chi(2)=15.62, d.f.=8, P=0.048), although the 1-d.f. test did not show the association for nine individual haplotypes when a P-value was corrected by the Bonferroni corrections. The present study suggests that the KPNA3 may contribute genetically to schizophrenia in a small effect size.

Adult↗
PubMed2003

Methods for analysis and visualization of SNP genotype data for complex diseases.

SNP markers are becoming central for studying genetic determinants of complex diseases. Large SNP data collected in such studies call for the development of specialized analysis tools. We present methods for selecting sets of SNPs that can be associated to sample properties in case/control studies. We also describe how scoring and selection can be statistically tested. This is done at the single locus as well as at the set level.

Bayes Theorem↗
PubMed2006

Frequent occurrence of uniparental disomy in colorectal cancer.

We used SNP arrays to identify and characterize genomic alterations associated with colorectal cancer (CRC). Laser microdissected cancer cells from 15 adenocarinomas were investigated by Affymetrix Mapping 10K SNP arrays. Analysis of the data extracted from the SNP arrays revealed multiple regions with copy number alterations and loss of heterozygosity (LOH). Novel LOH areas were identified at chromosomes 13, 14 and 15. Combined analysis of the LOH and copy number data revealed genomic structures that could not have been identified analyzing either data type alone. Half of the identified LOH regions showed no evidence of a reduced copy number, indicating the presence of uniparental structures. The distribution of these structures was non-random, primarily involving 8q, 13q and 20q. This finding was supported by analysis of an independent set of array-based transcriptional profiles, consisting of 17 normal mucosa and 66 adenocarcinoma samples. The transcriptional analysis revealed an unchanged expression level in areas with intact copy number, including regions with uniparental disomy, and a reduced expression level in the LOH regions representing factual losses (including 5q, 8p and 17p). The analysis also showed that genes in regions with increased copy number (including 7p and 20q) were predominantly upregulated. Further analyses of the SNP data revealed a subset of the identified alterations to be specifically associated with TP53 inactivation (including 8q gain and 17p loss) and lymph node metastasis status (gain of 7q and 13q). Another subset of the identified alterations was shown to represent intratumor heterogeneity. In conclusion, we demonstrate that uniparental disomy is frequent in CRC, and identify genomic alterations associated with TP53 inactivation and lymph node status.

Adenocarcinoma↗
PubMed2005

Genome-wide SNP discovery and linkage analysis in barley based on genes responsive to abiotic stress.

More than 2,000 genome-wide barley single nucleotide polymorphisms (SNPs) were developed by resequencing unigene fragments from eight diverse accessions. The average genome-wide SNP frequency observed in 877 unigenes was 1 SNP per 200 bp. However, SNP frequency was highly variable with the least number of SNP and SNP haplotypes observed within European cultivated germplasm reflecting effects of breeding history on genetic diversity. More than 300 SNP loci were mapped genetically in three experimental mapping populations which allowed the construction of an integrated SNP map incorporating a large number of RFLP, AFLP and SSR markers (1,237 loci in total). The genes used for SNP discovery were selected based on their transcriptional response to a variety of abiotic stresses. A set of known barley abiotic stress QTL was positioned on the linkage map, while the available sequence and gene expression information facilitated the identification of genes potentially associated with these traits. Comparison of the sequenced SNP loci to the rice genome sequence identified several regions of highly conserved gene order providing a framework for marker saturation in barley genomic regions of interest. The integration of genome-wide SNP and expression data with available genetic and phenotypic information will facilitate the identification of gene function in barley and other non-model organisms.

Expressed Sequence Tags↗
PubMed2006

Cyclic GMP-independent mechanisms contribute to the inhibition of platelet adhesion by nitric oxide donor: a role for alpha-actinin nitration.

The nitric oxide-mediated actions are mostly due to cyclic GMP (cGMP) formation, but cGMP-independent mechanisms, such as tyrosine nitration, have been suggested as potential signaling pathways modulating the NO-induced responses. However, the mechanisms that lead to tyrosine nitration in platelets are poorly studied, and the protein targets of nitration have not been identified in these cells. Therefore, we have used the model of platelet adhesion to fibrinogen-coated plates to investigate the cGMP-independent mechanisms of the NO-donor sodium nitroprusside (SNP) that leads to inhibition of platelet adhesion. SNP concentration-dependently inhibited platelet adhesion, as observed at 15-min and 60-min adhesion. Additionally, SNP markedly increased the cGMP levels, and the soluble guanylate inhibitor ODQ nearly abolished the SNP-mediated cGMP elevations in all experimental conditions used. Nevertheless, ODQ failed to affect the adhesion inhibition obtained with 1.0 mM SNP at 15 min. On the other hand, superoxide dismutase or peroxynitrite (ONOO(-)) scavenger epigallocatechin gallate significantly reversed the inhibition of platelet adhesion by SNP (1 mM, 15 min). Western blot analysis in SNP (1 mM, 15 min)-treated platelets showed a single tyrosine-nitrated protein with an apparent mass of approximately 105 kDa. Nanospray LC-MS/MS identified the human alpha-actinin 1 cytoskeletal isoform (P12814) as the protein contained in the nitrated SDS gel band. Thus, tyrosine nitration of alpha-actinin, through ONOO(-) formation, may be a key modulatory mechanism to control platelet adhesion.

Actinin↗
PubMed2007

Solution-phase DNA mutation scanning and SNP genotyping by nanoliter melting analysis.

Solution-phase, DNA melting analysis for heterozygote scanning and single nucleotide polymorphism (SNP) genotyping was performed in 10 nl volumes on a custom microchip. Human genomic DNA was PCR amplified in the presence of the saturating fluorescent dye, LCGreen Plus, and placed within microfluidic channels that were created between two glass slides. The microchip was heated at 0.1 degrees C/s with a Peltier device and viewed with an inverted fluorescence microscope modified for photomulitiplier tube detection. The melting data was normalized and the negative first derivative plotted against temperature. Mutation scanning for heterozygotes was easily performed by comparing the shape of the melting curve to homozygous standards. Genotyping of homozygotes by melting temperature (T(m)) required absolute temperature comparisons. Mutation scanning of ATM exon 17 and CFTR exon 10 identified single base change heterozygotes in 84 and 201 base-pair (bp) products, respectively. All genotypes at HFE C282Y were distinguished by simple melting analysis of a 40-bp fragment. Sequential analysis of the same sample on the gold-standard, commercial high-resolution melting instrument HR-1, followed by melting in a 10 nl reaction chamber, produced similar results. DNA melting analysis requires only minutes after PCR and is a simple method for genotyping and scanning that can be reduced to nanoliter volumes. Microscale systems for performing DNA melting reduce the reagents/DNA template required with a promise for high throughput analysis in a closed chamber without risk of contamination.

DNA↗
PubMed2000

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Alleles↗
PubMed2005

[Analysis and application of SNP and haplotype in the human genome].

Single nucleotide polymorphism (SNP) is the most common type of genetic variant in human genome. Haplotype, defined as a specific set of alleles observed on a single chromosome, or a part of a chromosome,has been an integral part of human genetics for decades. The goal of the international HapMap project is to determine the common patterns of DNA sequence variation and find the Tag SNPs representing all SNPs in the human genome. Some studies demonstrated that the analyses of haplotype defined by the grouping and interaction of several variants rather than any individual SNP correlated with complex phenotypes. Here, we describe the definitions of SNPs, genotype, haplotype and some information of the HapMap project. In this review, we summarize the current three haplotype-inference methods, including Clark' method, EM algorithm and Byes approach, and the different defining methods for haplotype block, as well as the methods for choosing tag SNPs and association studies of complex diseases using haplotype. The major public SNP databases and applications of SNPs and haplotype in common complex diseases and drug response are also introduced in the paper.

Algorithms↗
PubMed2006

Single nucleotide polymorphisms for integrative mapping in the Turkey (Meleagris gallopavo).

When multiple genetic maps exist for a species, integration of these maps requires a set of common markers be genotyped across the individual mapping populations. In the turkey, three genetic maps based on separate mapping populations are available. In this study, SNP-based markers were developed for integrating the cDNA/RFLP-based map (1) with microsatellite markers of the second-generation turkey genome map (2). Forty-eight primer sets were designed and tested and 33 (69%) correctly amplified turkey genomic DNA by PCR. Putative SNPs were detected in 20 (61%) of the amplified gene fragments, and 10 SNP markers were subsequently genotyped by PCR/RFLP for segregation analysis. Eight SNP markers were incorporated into the turkey genetic map.

Animals↗
PubMed2004

Pharmacogenetics of disease-modifying anti-rheumatic drugs.

The outcome of treatment with disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients is considerably variable and is also unpredictable. It would be useful clinically if physicians were able to predict responses to DMARDs prior to their administration. One possible cause of differences in efficacy and adverse drug reactions is genetic variation in how individuals metabolize drugs. Based on pharmacogenetics, tailor-made drug therapy, also called personalized drug therapy or individual drug therapy, will be possible with analysis of genetic polymorphism, such as single nucleotide polymorphism (SNP), and analysis of haplotype and diplotype configuration. Several studies of the correlation between the genetic polymorphism of enzymes metabolizing several DMARDs and efficacy or adverse drug reactions have already been reported, suggesting that pharmacogenetics will be applicable to the treatment of RA in the near future.

Antirheumatic Agents↗