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Results for “Single nucleotide polymorphisms”

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At least 505 records · Page 28Linked to original sources
PubMed2004

Identification and characterization of single-nucleotide polymorphisms in MCH-R1 and MCH-R2.

OBJECTIVE: To identify and functionally characterize single-nucleotide polymorphisms (SNPs) in melanin-concentrating hormone (MCH)-R1 and -R2. RESEARCH METHODS AND PROCEDURES: The entire coding regions and intron/exon splice junction regions of MCH-R1 and MCH-R2 were sequenced from anonymous white (n=45) and African-American (n=46) individuals. DNA was analyzed, and SNPs were identified using Phred, Phrap, and Consed software. DNA constructs containing MCH-R1 and MCH-R2 SNPs were generated and expressed in CHO cells. The effect of the SNPs in MCH-R1 and MCH-R2 were assessed in receptor binding assays and functional assays measuring changes in intracellular cAMP and Ca2+ levels. RESULTS: We identified 12 SNPs in the MCH-R1 gene. Two of these SNPs are in coding regions, and one produces an arginine-for-glycine substitution at residue 34 in the MCH-R1 sequence. This SNP is present at a minor allele frequency of 15% in the African-American population tested in this study. We identified eight SNPs in the MCH-R2 gene. Four of these SNPs are in coding regions, and two produce amino acid substitutions. Lysine substitutes for arginine at residue 63 of the African-American population, and glutamine substitutes for arginine at residue 152 in whites (minor allele frequency of 2% for both SNPs). No changes in receptor binding or functional signaling were observed with the SNP mutations in MCH-R1 or MCH-R2. DISCUSSION: These data indicate that potential therapeutics designed to act at the MCH receptor are unlikely to have altered effects in subpopulations that express variant forms of MCH-R1 or MCH-R2.

Amino Acid Sequence↗
PubMed2005

High-density single-nucleotide polymorphism maps of the human genome.

Here we report a large, extensively characterized set of single-nucleotide polymorphisms (SNPs) covering the human genome. We determined the allele frequencies of 55,018 SNPs in African Americans, Asians (Japanese-Chinese), and European Americans as part of The SNP Consortium's Allele Frequency Project. A subset of 8333 SNPs was also characterized in Koreans. Because these SNPs were ascertained in the same way, the data set is particularly useful for modeling. Our results document that much genetic variation is shared among populations. For autosomes, some 44% of these SNPs have a minor allele frequency > or =10% in each population, and the average allele frequency differences between populations with different continental origins are less than 19%. However, the several percentage point allele frequency differences among the closely related Korean, Japanese, and Chinese populations suggest caution in using mixtures of well-established populations for case-control genetic studies of complex traits. We estimate that approximately 7% of these SNPs are private SNPs with minor allele frequencies <1%. A useful set of characterized SNPs with large allele frequency differences between populations (>60%) can be used for admixture studies. High-density maps of high-quality, characterized SNPs produced by this project are freely available.

Alleles↗
PubMed2003

Single nucleotide polymorphisms in the XPG gene: determination of role in DNA repair and breast cancer risk.

In this study we determined the effect of single nucleotide polymorphisms in the XPG gene on DNA repair and breast cancer susceptibility. Ninety individuals, with previously studied DNA repair rate at 24 hr of 2 types of UV-specific cyclobutane pyrimidines dimers (CPDs) in skin were genotyped for XPG polymorphism at codon 1104 (exon 15 G>C; Asp > His). The repair rate of TT=C dimer was similar in both wild-type GG homozygotes and GC heterozygotes, whereas, for TT=T, dimer repair was non-significantly (Student's t-test, p = 0.34) lower in GC heterozygotes than wild-type GG homozygotes. Genotyping of 220 breast cancer cases and 308 controls for the same single nucleotide polymorphism in exon 15 of the XPG gene exhibited marginally significant increased frequency of the variant allele (chi(2) 3.84, p = 0.05; OR 1.33, 95% CI 1.0-1.8) in cases (C-allele 0.29) compared to controls (C-allele 0.24). Combined heterozygote and variant homozygote genotype frequency was also higher in cases than controls (chi(2) 4.79, p = 0.03; OR 1.50, 95%CI 1.04-2.16).

Adult↗
PubMed2005

Single nucleotide polymorphisms of the chicken insulin-like factor binding protein 2 gene associated with chicken growth and carcass traits.

Five single nucleotide polymorphisms (SNP) of the chicken insulin-like factor binding protein 2 (IGFBP2) gene were selected to genotype a F2 designed population with restriction fragment length polymorphisms and single stranded-conformation polymorphisms. The associations of the SNP and their haplotypes with chicken growth and carcass traits were analyzed. Results showed that the difference induced by the haplotypes derived from the 5 SNP was more significant than that by the single SNP in the genotype-phenotype association analysis. The haplotypes were associated with BW at hatch and at 21, 28, 42, 49, 56, and 90 d of age, as well as eviscerated weight with giblets (EWG), eviscerated weight (EW), and weights of heart, liver, and gizzard (HLGW) (P < or = 0.01). The haplotypes were also related to BW at 7, 14, and 35 d of age, breast depth, carcass weight, and breast muscle weight (P < or = 0.05). Significant and suggestive dominant effects of H1H5 diplotype were detected for BW at 7, 14, 21, 28, and 90 d of age, as well as breast depth, carcass weight, eviscerated weight with giblets, eviscerated weight, breast muscle weight, leg muscle weight, and weights of heart, liver, and gizzard. It was concluded that H1H5 was the most advantageous diplotype, and H4H10 was the negative diplotype for growth and carcass traits.

Animals↗
PubMed2000

Identification of new single-nucleotide polymorphisms in the thrombin receptor gene and their effects on coronary artery diseases in Koreans.

1. The thrombin receptor (the protease-activated receptor-1; PAR-1) is located on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the present study, we searched for genetic polymorphisms of the PAR-1 gene and evaluated their effects on CAD by association analysis. 2. We identified six polymorphisms in the 5'-untranslated region of the PAR-1 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP); five single-nucleotide polymorphisms (SNP) at -2355 (A to G), -2333 (T to G), -1428 (G to A), -1071 (C to T) and -561 (A to G) and a simple sequence repeat (SSR) polymorphism between -1935 and -1841. Five SNP were in strong linkage disequilibrium with each other to make three major haplotypes, the frequency of which was over 90% of all possible haplotypes. 3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects who had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population. The genotype frequencies of the SNP were in Hardy-Weinberg equilibrium, except A-561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR-1 gene in CAD in Koreans.

5' Untranslated Regions↗
PubMed2000

A simple procedure for the analysis of single nucleotide polymorphisms facilitates map-based cloning in Arabidopsis.

We developed a modified allele-specific PCR procedure for assaying single nucleotide polymorphisms (SNPs) and used the procedure (called SNAP for single-nucleotide amplified polymorphisms) to generate 62 Arabidopsis mapping markers. SNAP primers contain a single base pair mismatch within three nucleotides from the 3' end of one allele (the specific allele) and in addition have a 3' mismatch with the nonspecific allele. A computer program called SNAPER was used to facilitate the design of primers that generate at least a 1,000-fold difference in the quantity of the amplification products from the specific and nonspecific SNP alleles. Because SNAP markers can be readily assayed by electrophoresis on standard agarose gels and because a public database of over 25,000 SNPs is available between the Arabidopsis Columbia and Landsberg erecta ecotypes, the SNAP method greatly facilitates the map-based cloning of Arabidopsis genes defined by a mutant phenotype.

Alleles↗
PubMed2003

Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome.

OBJECTIVE: To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case-control study. SETTING: University-based clinic. PATIENT(S): One hundred twelve white women with PCOS and 115 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURES: The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm. RESULT(S): Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8). CONCLUSION(S): The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.

Case-Control Studies↗
PubMed2004

Identification of a single nucleotide polymorphism in the MMP-1 promoter in chondrosarcoma.

Matrix metalloproteinases (MMPs) are a group of at least 26 enzymes that facilitate cellular invasion via the degradation of the extracellular matrix. Specifically, the ability to degrade collagen types III and I is important in tumor invasion and metastasis. Over expression of the MMP-1 gene has been shown to correlate with poorer outcome in GI tract and gynecological tumors. This level of expression of this gene has been shown to be significantly increased by the presence of a single nucleotide polymorphism in the MMP-1 promoter sequence as a result of the creation of an ETS binding site. This SNP results from the addition of a single guanine base at -1,607 bp 24. Two chondrosarcoma cell lines and a series of 10 resected chondrosarcoma specimens underwent DNA extraction, purification, polymerase chain reaction, and sequencing. The presence of the single nucleotide polymorphism at -1,607 bp was confirmed within the promoter region for MMP-1 in human chondrosarcoma. Because all three genotypes were found in the clinical samples, the SNP may indeed provide a mechanistic explanation for a more aggressive biologic behavior locally and distally for a subset of chondrosarcomas.

Cell Line, Tumor↗
PubMed2002

Two bi-allelic single nucleotide polymorphisms within the promoter region of the horse tumour necrosis factor alpha gene.

Primers based on GenBank sequences within the 5' untranslated region (UTR) of the human and horse tumour necrosis factor alpha (TNF-alpha) genes were designed and used to amplify a 522-bp product. Sequencing of five clones derived from five independent PCRs obtained from three different animals of three different breeds (Old Kladruber, Akhal-Teke and Shetland Pony) revealed a high level of sequence identity to the TNF-alpha promoter regions of other species. The existing GenBank horse sequences were confirmed and extended upstream by 230 nucleotides. Based on the sequence obtained, a new horse-specific forward primer was designed to amplify a 213-bp PCR product, which was screened for polymorphism using single-strand conformation polymorphism (SSCP). Three allelic variants of the horse TNF-alpha gene were identified and sequenced (GenBank accession numbers ADF 349558-60). Two single nucleotide polymorphisms explained the existence of the three SSCP alleles detected: C/T and T/C single base pair substitutions at positions 137 and 147, respectively. Differences in allelic frequencies between Old Kladruber and Akhal-Teke breeds were observed.

5' Untranslated Regions↗
PubMed2000

Identification of a novel single nucleotide polymorphism (SNP) in the human organic cation transporter-like 2-antisense (ORCTL2S) gene.

We found a single nucleotide polymorphism (SNP) in exon 3 of the human organic cation transporter-like 2-antisense (ORCTL2S) gene: a base substitution A266G which was confirmed by direct sequencing. Heterozygosity of the polymorphic alleles was 0.45 in a Japanese population. This polymorphism will be useful in the allelic expression analysis of the ORCTL2S gene.

Carrier Proteins↗
PubMed2002

Quantification of PCR bias caused by a single nucleotide polymorphism in SMN gene dosage analysis.

Approximately 94% of patients with spinal muscular atrophy lack both copies of SMN1 exon 7, and most carriers have only one copy of SMN1 exon 7. We described previously the effect of SMN1/SMN2 heteroduplex formation on SMN gene dosage analysis, which is a multiplex quantitative PCR assay to determine the copy numbers of SMN1 and SMN2 using DraI digestion to differentiate SMN2 from SMN1. We describe herein the quantification of PCR bias between SMN1 exon 7 and SMN2 exon 7, which differ by only one nucleotide that is not present in either primer binding site. Using samples from 272 individuals with various SMN genotypes, we found that the amplification efficiency of SMN2 was consistent only approximately 80% that of SMN1. Thus, even a single nucleotide polymorphism, not in primer binding sites, can cause reproducible PCR bias. The precision and accuracy of our SMN gene dosage analysis are high because our assay design and controls take advantage of the consistency of the PCR bias. As additional clinically significant single nucleotide polymorphisms (SNPs) are discovered, assessment of PCR bias, and judicious selection of standards and controls, will be increasingly important for quantitative PCR assays.

Bias↗