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Results for “single nucleotide polymorphisms”

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PubMed2006

Single-nucleotide polymorphisms in porcine mannan-binding lectin A.

The MBL1 and MBL2 genes encode mannan-binding lectins (MBL) A and C, respectively, that are collagenous lectins (collectins) produced mainly by the liver. Several single-nucleotide polymorphisms (SNPs) in the human MBL2 gene are responsible for various innate immune dysfunctions due to abnormal structure or expression of human MBL-C. The MBL1 gene encodes MBL-A, which has bacteria-binding properties in pigs and rodents but is mutated to a pseudogene in humans and chimpanzees. In these studies, we surveyed both porcine MBL genes for SNPs that might impair disease resistance. Single-strand conformational polymorphism (SSCP) analysis of MBL cDNAs from porcine liver revealed three SNPs within the coding region of MBL1 in various breeds of pigs. One nonsynonymous SNP that substituted cysteine for glycine in the collagen-like domain of pig MBL-A was found by a multiplex PCR test in all European pig breeds examined, with allele frequencies ranging from 1.4 to 46.4%. No SNPs were identified in the coding region of porcine MBL2 but the expression of MBL-C in the liver was widely variable in comparison to the expression of MBL-A, GAPDH, PigMAP, and haptoglobin. These results indicate that some pigs have a miscoding defect in MBL-A and a possible expression defect in MBL-C, which are analogous to coding and promoter polymorphisms that affect human MBL-C.

Amino Acid Sequence↗
PubMed2006

Improvements in the analysis strategy make single nucleotide polymorphism analysis a powerful tool in the detection and characterization of amplified chromosomal regions in human tumors.

OBJECTIVE: Single nucleotide polymorphism analysis (SNP) has recently been proposed as an alternative technique to comparative genomic hybridization (CGH) for defining loss of heterozygosity and gene copy number changes in a single experimental setup. In order to assess the potential of SNP analysis to complement or, ultimately, substitute CGH results, we applied both techniques to five primary tumor samples and two tumor cell lines. This was complemented by dilution experiments based on normal lymphocyte DNA to decipher the lower detection limit for genetic alterations. METHODS/RESULTS: Using an in-house software tool, we demonstrated that SNP analysis permits the generation of chromosomal alteration patterns that largely resemble conventional CGH ratio profiles of a given tumor/cell line. Moreover, compared to CGH, our SNP software tool allows a much more detailed definition of amplicon sizes and involved candidate genes. This advantage even persisted when the technique was applied to DNA with more than 60% of nontumor content. However, the detection of chromosomal losses is severely hampered by the presence of nontumor DNA so that the use of the SNP technique should be limited to tumor samples with more than 80% tumor DNA. CONCLUSION: SNP analysis is a very valuable tool for the detection and characterization of high-level chromosomal amplifications in the vast majority of primary tumor samples. Our software tool improves the analysis of SNP data and the presentation of the results, bridging the gap to existing CGH knowledge (http://bioinformatics.uni-muenster.de, 'Publications and Supplements').

Algorithms↗
PubMed2006

[Methods for detecting single nucleotide polymorphisms: allele-specific PCR and hybridization with oligonucleotide probe].

The existing diversity of the methods for detecting single nucleotide polymorphisms is so great that may perplex an unsophisticated researcher who chooses the appropriate molecular genetic toolkit. In this work, we tried to systematize and briefly describe the state-of-the-art methods for detecting oligonucleotide polymorphisms that are based on allele-specific PCR and hybridization with oligonucleotide probe as well as to characterize the methods considered with respect to their accuracy, cost, and simplicity.

Alleles↗
PubMed2001

Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation.

We have developed a formalism and a computational method for analyzing the potential functional consequences of non-synonymous single nucleotide polymorphisms. Our approach uses a structural model and phylogenetic information to derive a selection of structure and sequence-based features serving as indicators of an amino acid polymorphim's effect on function. The feature values can be integrated into a probabilistic assessment of whether an amino acid polymorphism will affect the function or stability of a target protein. The method has been validated with data sets of unbiased mutations in the lac repressor and lysoyzyme. Applying our methodology to recent surveys of genetic variation in the coding regions of clinically important genes, we estimate that approximately 26-32 % of the natural non-synonymous single nucleotide polymorphisms have effects on function. This estimate suggests that a typical person will have about 6240-12,800 heterozygous loci that encode proteins with functional variation due to natural amino acid polymorphism.

Amino Acids↗
PubMed2006

Association study with 33 single-nucleotide polymorphisms in 11 candidate genes for hypertension in Chinese.

Essential hypertension is considered to be a typical complex disease with multifactorial etiology, which leads to inconsistent findings in genetic studies. One possibility of failure to replicate some single-locus results is that the underlying genetics of hypertension are not only based on multiple genes with minor effects but also on gene-gene interactions. To test this hypothesis, a case-control study was constructed in Chinese subjects, detecting both single locus and multilocus effects. Eleven candidate genes were selected from biochemical pathways that have been implicated in the development and progression of hypertension, and 33 polymorphisms were evaluated in 503 hypertension patients and 490 age- and gender-matched controls. Single-locus associations, using traditional logistic regression analyses, and multilocus associations, using classification and regression trees and multivariate adaptive regression splines, were both explored in this study. Final models were selected using either Bonferroni correction or cross-validation. Three polymorphisms, TH*rs2070762, ADRB2*Q27E, and GRK4*A486V, were found to be independently associated with essential hypertension in Chinese subjects. In addition to these individual predictors, a potential interaction of CYP11B2-AGTR1 is also involved in the etiology of hypertension. These findings support the multigenic nature of the etiology of essential hypertension and propose a potential gene-gene interactive model for future studies.

Alanine↗
PubMed2003

Typing single-nucleotide polymorphisms using a gel-based sequencer: a new data analysis tool and suggestions for improved efficiency.

Single-nucleotide polymorphisms (SNPs) are increasingly used as genetic markers. Although a high number of SNP-genotyping techniques have been described, most techniques still have low throughput or require major investments. For laboratories that have access to an automated sequencer, a single-base extension (SBE) assay can be implemented using the ABI SNaPshot trade mark kit. Here we present a modified protocol comprising multiplex template generation, multiplex SBE reaction, and multiplex sample analysis on a gel-based sequencer such as the ABI 377. These sequencers run on a Macintosh platform, but on this platform the software available for analysis of data from the ABI 377 has limitations. First, analysis of the size standard included with the kit is not facilitated. Therefore a new size standard was designed. Second, using Genotyper (ABI), the analysis of the data is very tedious and time consuming. To enable automated batch analysis of 96 samples, with 10 SNPs each, we developed SNPtyper. This is a spreadsheet-based tool that uses the data from Genotyper and offers the user a convenient interface to set parameters required for correct allele calling. In conclusion, the method described will enable any lab having access to an ABI sequencer to genotype up to 1000 SNPs per day for a single experimenter, without investing in new equipment.

Computational Biology↗
PubMed2003

Associations between single nucleotide polymorphisms in candidate genes and growth rate in Arctic charr (Salvelinus alpinus L.).

We tested for associations between single nucleotide polymorphisms (SNPs) in five candidate genes allied with the growth hormone axis and the age-specific growth rate of Arctic charr (Salvelinus alpinus L.: Salmonidae). Two large full sib families (N=217 and 95) were created by backcrossing males that were hybrids between two phenotypically divergent populations from Labrador, Canada and from Nauyuk Lake, Canada to females that were from Nauyuk Lake. Measures of individual growth rate (wet weight and fork length) were made three times during a 420-day period after the juveniles were transferred from 4 to 11 degrees C. We then identified SNP markers in 10 proposed candidate genes known to be related to the growth hormone axis. Comparative alignments of amino-acid sequences and nucleotide sequences from other fish species were used to design PCR primers that would amplify 0.5-3 kb DNA regions of the candidate genes. All the individuals in the two backcross families were genotyped for these SNP markers using either polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or bidirectional amplification of specific alleles (Bi-PASA) approaches. A significant association between a particular SNP allele and early growth was found for the locus containing the growth hormone-releasing hormone and pituitary adenylate cyclase-activating polypeptide genes (GHRH/PACAP2, P=0.00001). We argue that using comparative sequence information to design PCR primers for candidate genes is an efficient method for locating quantitative triat loci in nonmodel organisms.

Animals↗
PubMed2006

PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes.

We have developed a web tool, PupaSuite, for the selection of single nucleotide polymorphisms (SNPs) with potential phenotypic effect, specifically oriented to help in the design of large-scale genotyping projects. PupaSuite uses a collection of data on SNPs from heterogeneous sources and a large number of pre-calculated predictions to offer a flexible and intuitive interface for selecting an optimal set of SNPs. It improves the functionality of PupaSNP and PupasView programs and implements new facilities such as the analysis of user's data to derive haplotypes with functional information. A new estimator of putative effect of polymorphisms has been included that uses evolutionary information. Also SNPeffect database predictions have been included. The PupaSuite web interface is accessible through http://pupasuite.bioinfo.cipf.es and through http://www.pupasnp.org.

Algorithms↗
PubMed2003

Simultaneous genotyping of multiplex single nucleotide polymorphisms of the K-ras gene with a home-made kit.

Accurate and fast genotyping of single nucleotide polymorphisms (SNPs) is important in the human genome project. Here an automated fluorescent method that can rapidly and accurately genotype multiplex known SNPs was developed by using a homemade kit, which has lower cost but higher resolution than commercial kit. With this method, oncogene K-ras was investigated, four known SNPs of K-ras gene exon 1 in 31 coloerctal cancer patients were detected. Results indicate that mutations were present in 8(26%) of 31 patients, and most mutations were localized in codon 12. The presence of these mutations is thought to be a critical step and plays an important role in human colorectal carcinogenesisas.

Base Sequence↗
PubMed2006

[Study of mutation and single nucleotide polymorphism of PDGFRbeta and SHIP gene in acute myeloid leukemia].

OBJECTIVE: To investigate the significance of mutation and single nucleotide polymorphism (SNP) of class III receptor tyrosine kinases such as PDGFRbeta and SHIP in acute myeloid leukemia (AML) patients. METHODS: Screening of the mutation and SNP of PDGFRbeta and SHIP by genomic PCR, RT-PCR, directly sequencing and Mass-ARRAY system was carried out in 273 AML patients. RESULTS: The mutations of PDGFRbeta R685C and SHIP Q1153L were detected for the first time in AML patients. The positivity ratio was 0.73% and 0.36% respectively. CONCLUSION: The mutations of PDGFRbeta R685C and SHIP Q1153L may contribute to leukemogenesis of AML.

Humans↗
PubMed2002

Association of a novel single nucleotide polymorphism of the prostacyclin synthase gene with myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a complex multifactorial and polygenic disorder that is thought to result from an interaction between an individual's genetic makeup and various environmental factors. The purpose of this study was to investigate the association between a novel single nucleotide polymorphism in the prostacyclin synthase gene and MI. METHODS AND RESULTS: By the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we identified a single nucleotide polymorphism, C1117A, in exon 8. This nucleotide change did not cause an amino acid change in codon 373. We performed an association study of the polymorphism in 138 patients and 130 healthy control subjects. Multiple logistic linear regression analysis showed the genotype distributions were significantly different between the control group and the MI group (odds ratio, 2.12; 95% CI, 1.47-3.05, P =.04). The C/C genotype was found more frequently in the MI group than in the control group. CONCLUSIONS: We conclude that the C1117A polymorphism in exon 8 is associated with risk for MI and may be a genetic marker of MI in Japanese persons.

Case-Control Studies↗
PubMed2005

Identification of genetic markers for fat deposition and meat tenderness on bovine chromosome 5: development of a low-density single nucleotide polymorphism map.

As genetic markers, SNP are well suited for the development of genetic tests for production traits in livestock. They are stable through many generations and can provide direct assessment of individual animal's genetic merit if they are in linkage disequilibrium and phase with functional genetic variation. Bovine chromosome 5 has been shown to harbor genetic variation affecting production traits in multiple cattle populations; thus, this chromosome was targeted for SNP-based marker development and subsequent association analysis with carcass and growth phenotypes. Discovery of SNP was performed in a panel of 16 sires representing two sires from each of seven beef breeds and two Holstein sires by PCR amplification and sequencing using primers designed from genomic sequence obtained by low-coverage sequencing of bacterial artificial chromosome (BAC) clones. From 550 SNP, 296 (54%) were tentatively identified as having a minor allele frequency >10%. Forty-five SNP derived from 15 BAC were chosen based on minor allele frequency and were genotyped in 564 steers and their sires. Production and carcass data were collected on the steers as a part of the Germplasm Evaluation (GPE), Cycle VII Project at the U.S. Meat Animal Research Center (Clay Center, NE), which involves of the evaluation of sires from seven of the most popular U.S. breeds. Haplotypes based on seven SNP derived from a BAC containing the bovine genes HEM1 and PDE1B were associated with traits related to carcass fat. Steers homozygous for the major haplotype had 0.15 +/- 0.04 cm less subcutaneous fat, 0.57 +/- 0.18 kg less rib fat, 0.18 +/- 0.07 lower yield grade, 1.11 +/- 0.35% less predicted fat yield, and 0.79 +/- 0.3% greater predicted retail product yield than heterozygotes. The frequency of the major haplotype was 0.70 in the steers, and it ranged from 0.44 (Limousin) to 0.98 (Simmental and Gelbvieh) in a panel consisting of an average of 20 purebred sires from each of the seven breeds. A second set of haplotypes based on four SNP derived from a BAC containing the genes NOL1 and CHD4 was associated with Warner-Bratzler shear force. Steers homozygous for the major haplotype had 0.27 +/- 0.11 kg greater shear force than those heterozygous for the major haplotype and one of two minor haplotypes. The frequency of the major haplotype was 0.59 in the steers and ranged from 0.27 (Hereford) to approximately 0.95 (Angus and Red Angus) in the panel of purebred sires. These results demonstrate the feasibility of targeting QTL regions for SNP-based marker development and that a low level of coverage can identify markers associated with phenotypic traits.

Adipose Tissue↗