Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SNPs”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed2006

IL-10 promoter and IL4-Ralpha gene SNPs are associated with immediate beta-lactam allergy in atopic women.

BACKGROUND: Allergic reactions to beta-lactam antibiotics represent the most frequent cause of immunological drug reactions. OBJECTIVE: This study evaluates the involvement of genetic susceptibility factors in patients with immediate allergic reactions to beta-lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation. METHODS: We performed a case-control study involving 44 patients with immediate beta-lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)-4, IL-13, IL-4Ralpha, signal transducer and activator of transcription 6 (STAT6), interferon (IFN)-gammaR1, IFN-gammaR2 and FcepsilonRIbeta gene polymorphisms were determined using polymerase chain reaction (PCR) restriction fragment length polymorphism, and IL-21R gene and IL-10 promoter polymorphisms by direct sequencing. RESULTS: Our analysis did not reveal differences in the distribution of the 15 SNPs between allergic patients and controls. However, among atopic subjects, we found two distinct significant associations between immediate beta-lactam allergy in women and the Ile75Val variant of IL-4Ralpha gene (P = 0.012, OR = 5.4, CI: 1.16-27.7), and two linked IL-10 promoter gene polymorphisms, -819C>T and -592 C>A (P = 0.023, OR = 17.5, CI: 1.26-533.07). In contrast, we observed no association in allergic male subjects in the atopic population. Interestingly, the IL-4Ralpha Ile75Val variant could have a paradoxal protective effect in atopic male patients (P = 0.004, OR = 0.07, CI: 0.01-0.66). CONCLUSION: Our findings suggest that polymorphisms in the IL-10 promoter and IL-4Ralpha genes are genetic factors that favour beta-lactam immediate allergies in female patients with atopy.

Adolescent↗
PubMed2006

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children.

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.

Adolescent↗
PubMed2003

Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls.

beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They exhibit antibacterial, antifungal, and antiviral properties. Defensins are a component of the innate immune response, and it has been proposed that they have a protective role in the oral cavity. Previous studies have shown that human beta-defensin 1 (hBD-1) is constitutively expressed in oral epithelial cells but that expression varies between individuals. We tested the hypothesis that genetic variations in defensin peptide expression may be associated with opportunistic infections. This may be critical in the immunocompromised patient population, in which innate immune responses may have a relatively more important role. Oral Candida carriage status and the presence of six single-nucleotide polymorphisms (SNPs) in the DEFB1 gene encoding hBD-1 were evaluated in type I diabetic patients (n = 43) and nondiabetic controls (n = 50). Genomic DNA was obtained from buccal swabs. Portions of the DEFB1 gene were amplified, and each SNP was analyzed by a TaqMan assay, standardized with control DNA of known genotype. Candida carriage status was determined from unstimulated saliva on CHROMagar plating medium. A low level of Candida carriage was defined as < or = 350 CFU/ml. A high level of Candida carriage was seen in 44% of the diabetic subjects but only in 28% of the nondiabetic controls (P < 0.05). C. albicans predominated; however, diabetic subjects, especially those with high levels of carriage, showed an increased proportion of Candida glabrata and C. tropicalis. There was a strong association between an SNP in the 5' untranslated region (C-->G at position -44) and Candida carriage in both groups. Among individuals in the diabetic population who had the SNP allele 2 (G), 58% had low CFU, while 6% had high CFU. The C-->G SNP at position -44 is associated with low levels of Candida carriage. The resultant odd ratios are statistically significant for a protective effect (odd ratios, 25 for diabetic subjects and 8.5 for nondiabetic subjects). These results indicate that genetic variations in the DEFB1 gene encoding hBD-1 may have a major role in mediating and/or contributing to susceptibility to oral infection.

Adolescent↗
PubMed2004

Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium.

The agouti related protein (AgRP) exerts its anabolic effects on food intake by antagonising the alpha-melanocyte stimulating hormone (alpha-MSH) at its receptors, melanocortin receptors 3 and 4 (MC3R and MC4R). A single nucleotide polymorphism (SNP) in the promoter of the human AgRP (hAgRP), -38C>T, was associated with low body fatness. The -38T allele that was associated with low body fatness also resulted in lower promoter activity. Here we report a novel SNP, -3019G>A, again in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the -38C>T SNP (linked alleles: -3019A/-38T and -3019G/-38C). Functional analyses in a human adrenal and two mouse hypothalamus cell lines showed that the -3019A allele had significantly higher promoter activity. Hence, the two linked alleles (-3019A and -38T) had opposite effects on promoter function and yet they were both associated with low body fatness. The region encompassing the -38C>T SNP had approximately 1000-fold higher activity than the region encompassing the -3019G>A SNP, potentially determining the net functional effect between these two SNPs.

Agouti-Related Protein↗
PubMed2002

Detection rates for genotyping errors in SNPs using the trio design.

One well-known approach for the analysis of transmission-disequilibrium is the investigation of single nucleotide polymorphisms (SNPs) in trios consisting of an affected child and its parents. Results may be biased by erroneously given genotypes. Various reasons, among them sample swap or wrong pedigree structure, represent a possible source for biased results. As these can be partly ruled out by good study conditions together with checks for correct pedigree structure by a series of independent markers, the remaining main cause for errors is genotyping errors. Some of the errors can be detected by Mendelian checks whilst others are compatible with the pedigree structure. The extent of genotyping errors can be estimated by investigating the rate of detected genotyping errors by Mendelian checks. In many studies only one SNP of a specific genomic region is investigated by TDT which leaves Mendelian checks as the only tool to control genotyping errors. From the rate of detected errors the true error rate can be estimated. Gordon et al. [Hum Hered 1999;49:65-70] considered the case of genotyping errors that occur randomly and independently with some fixed probability for the wrong ascertainment of an allele. In practice, instead of single alleles, SNP genotypes are determined. Therefore, we study the proportion of detected errors (detection rate) based on genotypes. In contrast to Gordon et al., who reported detection rates between 25 and 30%, we obtain higher detection rates ranging from 39 up to 61% considering likely error structures in the data. We conclude that detection rates are probably substantially higher than those reported by Gordon et al.

Genotype↗
PubMed2003

Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study.

We describe an approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes. Based on a preliminary sample of 70 control subjects chosen at random from each of the 5 ethnic groups in the MEC we estimate haplotype frequencies using a variant of the Excoffier-Slatkin E-M algorithm after genotyping a high density of SNPs selected every 3-5 kb in and surrounding a candidate gene. In order to evaluate the performance of a candidate set of htSNPS (which will be genotyped in the much larger case-control sample) we treat the haplotype frequencies estimate above as known, and carry out a formal calculation of the uncertainty of the number of copies of common haplotypes carried by an individual, summarizing this calculation as a coefficient of determination, R2h. A candidate set of htSNPS of a given size is chosen so as to maximize the minimum value of R2h over the common haplotypes, h.

Aromatase↗
PubMed2006

A simple model of linkage disequilibrium and genetic drift in human genomic SNPs: importance of demography and SNP age.

We propose a simple model of evolution at a pair of SNP loci, under mutation, genetic drift and recombination. The developed model allows to consider evolution of SNPs under different demographic scenarios. We applied it to SNP data containing polymorphisms spanning 19 gene regions. We initially matched the linkage disequilibrium (LD) data only, and then we reconciled both LD and heterozygosity data. The imbalance between LD and heterozygosity data, observed for some of the analyzed genomic regions, may be a signature of selection acting in these regions. However, assuming neutrality, we obtain estimates of the age of population expansion of modern humans, which are consistent with the consensus estimates. In addition, we are able to estimate the ages of the polymorphisms observed in different genomic regions and we find that they vary widely with respect to their age. Polymorphisms at loci implicated in human disease, seem to be younger than average. Our results supplement the conclusions originally obtained by Reich and co-workers for the same set of data.

Genetic Drift↗
PubMed2006

Isolation, mapping and identification of SNPs for four genes (ACP6, CGN, ANXA9, SLC27A3) from a bovine QTL region on BTA3.

On the basis of fine mapping of a quantitative trait loci region of BTA3 for milk fat content, an examination of the comparative map between cattle and human indicates that the annexin 9 protein gene (ANXA9) and the fatty acid transport protein type 3 gene (SLC27A3) are two strong candidate genes. The objective of the present study is to isolate, map and characterize these genes and identify polymorphisms that could be further utilized in linkage or association studies. Furthermore, two new genes which are in the same region, cingulin protein gene (CGN) and lysophosphatidic acid phosphatase protein gene (ACP6) were studied. DNA fragments (869, 1778, 1933 and 2618 bp) corresponding to partial sequences of ACP6,CGN,ANXA9 and SLC27A3 genes were isolated. Direct sequencing of PCR products amplified from different cattle breeds revealed 1, 4, 4 and 2 SNPs for ACP6, CGN,ANXA9 and SLC27A3, respectively. For ANXA9 one SNP was located in exon 5 (A-->G 951) resulting in an amino acid change from histidine to arginine. Finally, ACP6,CGN,ANXA9 and SLC27A3 genes were located on chromosome 3 between ILSTS096 and BMS819 markers, in a region in which quantitative trait loci (QTL) for several milk traits have been described.

3' Untranslated Regions↗
PubMed2004

Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene.

PURPOSE: To study some functional candidate genes in cataract families of Indian descent. METHODS: Nine Indian families, clinically documented to have congenital/childhood cataracts, were screened for mutations in candidate genes such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing. Genomic DNA samples of either probands or any representative affected member of each family were PCR amplified and sequenced commercially. Documentation of single nucleotide polymorphisms (SNPs) and candidate mutations was done through BLAST SEARCH (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?). RESULTS: Several single nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed. Because they do not co-segregate with the phenotype, they were excluded as candidates for the cataract formation in these patients. However, a substitution (W151C in exon 6 of CRYBB2) was identified as the most likely causative mutation underlying the phenotype of central nuclear cataract in all affected members of family C176. Protein structural interpretations demonstrated that no major structural alterations could be predicted and that even the hydrogen bonds to the neighboring Leu166 were unchanged. Surprisingly, hydropathy analysis of the mutant betaB2-crystallin featuring the amino acids at position 147 to 155, further increased the hydrophobicity, which might impair the solubility of the mutant protein. Finally, the Cys residue at position 151 might possibly be involved in intramolecular disulphide bridges with other cysteines during translation, possibly leading to dramatic structural changes. CONCLUSIONS: Exon 6 of CRYBB2 appears to be a critical region susceptible for mutations leading to lens opacity.

Adolescent↗
PubMed2005

Genotyping DNA pools on microarrays: tackling the QTL problem of large samples and large numbers of SNPs.

BACKGROUND: Quantitative trait locus (QTL) theory predicts that genetic influence on complex traits involves multiple genes of small effect size. To detect QTL associations of small effect size, large samples and systematic screens of thousands of DNA markers are required. An efficient solution is to genotype case and control DNA pools using SNP microarrays. We demonstrate that this is practical using DNA pools of 100 individuals. RESULTS: Using standard microarray protocols for the Affymetrix GeneChip Mapping 10 K Array Xba 131, we show that relative allele signal (RAS) values provide a quantitative index of allele frequencies in pooled DNA that correlate 0.986 with allele frequencies for 104 SNPs that were genotyped individually for 100 individuals. The sensitivity of the assay was demonstrated empirically in a spiking experiment in which 15% and 20% of one individual's DNA was added to a DNA pool. CONCLUSION: We conclude that this approach, which we call SNP-MaP (SNP microarrays and pooling), is rapid, cost effective and promises to be a valuable initial screening method in the hunt for QTLs.

Alleles↗
PubMed2004

Single-track sequencing for genotyping of multiple SNPs in the N-acetyltransferase 1 (NAT1) gene.

BACKGROUND: Fast, cheap and reliable methods are needed to identify large populations, which may be at risk in relation to environmental exposure. Polymorphisms in NAT1 (N-acetyl transferase) may be suitable markers to identify individuals at risk. RESULTS: A strategy allowing to address simultaneously 24 various genetic variants in the NAT1 gene using the single sequencing reaction method on the same PCR product is described. A modified automated DNA sequencing using only one of the sequence terminators was used to genotype PCR products in single-track sequencing reactions of NAT1 and was shown to be universal for both DNA sequencing using labeled primers and labeled nucleotides. By this method we detected known SNPs at site T640G, which confers the NAT1*11 allele with frequency of 0.036, further T1088A and C1095A with frequency of 0.172 and 0.188, respectively and a deletion of TAATAATAA in the poly A signal area with a frequency 0.031. All observed frequencies were in Hardy Weinberg equilibrium and comparable to those in Caucasian population. The single-track signatures of the variant genotypes were verified on samples previously genotyped by RLFP. CONCLUSIONS: The method could be of great help to scientists in the field of molecular epidemiology of screening of large populations for known informative biomarkers of susceptibility, such as NAT1.

Arylamine N-Acetyltransferase↗
PubMed2005

The use of genetic SNPs as new diagnostic markers in preventive medicine.

Using an automated mass spectrometric genotyping platform, we have completed more than ten whole-genome SNP scans on phenotypically stratified population pools. The pools are usually constructed to represent one ethnicity, one gender, and one phenotype, classified as strictly as possible. From 28,000 to 91,000 different SNPs are used for each study, and the pools typically contain DNA from 300 different individuals. Significant correlations between SNP allele and phenotype are first reproduced in the pools, then replicated on individual DNA samples (deconvolution of the pools), and then where possible replicated in completely independent populations.

A Kinase Anchor Proteins↗
PubMed2005

Genome-wide linkage disequilibrium from 100,000 SNPs in the East Finland founder population.

Information about linkage disequilibrium (LD) is important in understanding the genome structure and has its applications in association studies. Here we present the first genome-wide LD study based on a founder population (East Finland). The LD data consist of 118 unrelated individuals and around 480,000 SNP pairs genotyped with the Affymetrix 100K genotyping assay. Using the minor allele frequency (MAF) limit of .05, the squared correlation coefficient between two loci (r(2)) was .48, .37, .28, and .20 for distances of 5, 10, 20, and 40 kb respectively. MAF had a significant effect on the mean r(2) so that the extent of useful LD (r(2) > .3) varied from 17 kb to 80 kb depending on the limit set for the MAF. For D' the effect of MAF was smaller but reflected the possible age of the mutation: SNPs with high MAF had lower D' than those with low MAF. The X chromosome showed higher D' values than autosomes and the extent of useful LD (r(2) > .3) was twice as long on the X chromosome than on the autosomes. Based on the results, LD varies across the genome and is correlated to local recombination rate between and within chromosomes. However, the recombination rate does not explain all the variation found in LD. We also report a number of long chromosomal regions where exceptionally high or low LD were detected.

Alleles↗
PubMed2005

Typing of Y chromosome SNPs with multiplex PCR methods.

We describe a method for the simultaneous typing of Y-chromosome single nucleotide polymorphism (SNP) markers by means of multiplex polymerase chain reaction (PCR) strategies that allow the detection of 35 Y chromosome SNPs on 25 amplicons from 100 to 200 pg of chromosomal deoxyribonucleic acid (DNA). Multiplex PCR amplification of the DNA was performed with slight modifications of standard PCR conditions. Single-base extension (SBE) was performed using the SNaPshot kit containing fluorescently labeled ddNTPs. The extended primers were detected on an ABI 3100 sequencer. The most important factors for the creation of larger SNP typing PCR multiplexes include careful selection of primers for the primary amplification and the SBE reaction, use of DNA primers with homogenous composition, and balancing the primer concentrations for both the amplification and the SBE reactions.

Base Sequence↗
PubMed2004

Three novel single nucleotide polymorphisms (SNPs) of the CYP2B6 gene in Japanese individuals.

We sequenced all exons and exon-intron junctions of the CYP2B6 gene from 200 Japanese individuals. We found three novel single nucleotide polymorphisms (SNPs) (1375A>G, 1427G>A and 1454A>T) causing amino acid substitutions (Met(459)Val, Gly(476)Asp and Gln(485)Leu in exon 9), respectively. The detected SNP was as follows: 1) SNP, 031226Hiratsuka01; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CAGAACTTCTCCA/GTGGCCAGCCCCG-3'. 2) SNP, 031226Hiratsuka02; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CCCAGGAGTGTGG/ATGTGGGCAAAAT-3'. 3) SNP, 031226Hiratsuka03; GENE NAME, CYP2B6; ACCESSION NUMBER, AC023172; LENGTH, 25 base; 5'-CCCCAACATACCA/TGATCCGCTTCCT-3'.

Amino Acid Substitution↗
PubMed2001

High-throughput conformation-sensitive gel electrophoresis for discovery of SNPs.

High-throughput screening for single nucleotide polymorphisms (SNPs) or mutations can be achieved by inexpensive technologies. We modified the original protocols of conformation-sensitive gel electrophoresis (CSGE) to increase throughput several fold to 1.3 samples/min, which is about five times faster than denaturing high-performance liquid chromatography (DHPLC). The modifications include decreasing the gel thickness, increasing the number of lanes to 96, and increasing the number of samples per lane to seven. This high-throughput CSGE method is fast, robust, and as simple as the original protocols. Together with a two-stage strategy for screening homozygotes and the replacement of ethidium bromide with SYBR Gold DNA dye staining, this protocol is a reliable and cost-effective alternative for laboratories that require high-throughput screening.

Heterozygote↗
PubMed2001

Melting curve analysis of SNPs (McSNP): a gel-free and inexpensive approach for SNP genotyping.

High-throughput methods for assaying DNA variation require two important steps: (i) discriminating the variation and (ii) detecting the signal. In this report, we describe a novel SNP genotyping method that we refer to as melting curve analysis of SNPs (McSNP). McSNP combines a classic approach for discriminating alleles, restriction enzyme digestion, with a more recent method for detecting DNA fragments, melting curve analysis. Melting curve analysis is performed by slowly heating DNA fragments in the presence of the dsDNA-specific fluorescent dye SYBR Green I. As the sample is heated, fluorescence rapidly decreases when the melting temperature of a particular fragment is reached. We show that it is possible to determine the composition of simple mixtures of DNA fragments, such as those that result from restriction enzyme digestions of short PCR products. McSNP is well suited for high-throughput genotyping because 96 samples can be analyzed and automatically scored in 20 min. Our results clearly demonstrate that McSNP is a simple, inexpensive, and accurate means of genotyping SNP variation.

Genotype↗
PubMed2026

Microsatellites Versus Genome-Wide SNPs Data for Pedigree Reconstruction in Twin Simmental Crossbred Cattle.

Accurate pedigree reconstruction is critical for genetic evaluation in admixed cattle populations, yet the relative performance of microsatellite and genome-wide SNP markers in twin-rich herds with incomplete pedigree records remains unclear. We compared 12 ISAG-recommended microsatellite markers with whole-genome SNP data for dam-calf assignment in a Simmental crossbred population (n = 43, 13 dam-calf groups) from southern China. Twin zygosity was determined from SNP identity-by-descent (PI_HAT) values: nine calf pairs were dizygotic, one pair was monozygotic (20A/21A), and one adult pair was composed of dizygotic twin sisters (31A/34A). Admixture analysis at K = 3 revealed ancestry proportions of 50.7% European taurine, 28.9% Chinese indicine and 20.4% East Asian taurine. The SNP-based neighbor-joining tree correctly recovered 12 of 13 groups (92.3%, 95% CI: 64.0-99.8%), whereas the microsatellite-based tree recovered 11 (84.6%, 95% CI: 54.6-98.1%); the difference was not statistically significant (exact McNemar test, p = 1.0). Locus INRA023 was monomorphic (PIC = 0), reducing the effective number of markers to 11. These results indicate that genome-wide SNPs show a favourable trend in accuracy and are less prone to false-positive clustering than a standard microsatellite panel in admixed, twin-rich cattle populations.

SNP↗