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Results for “single nucleotide polymorphisms”

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At least 685 records · Page 38Linked to original sources
PubMed2005

Genome-wide single nucleotide polymorphism analysis reveals frequent partial uniparental disomy due to somatic recombination in acute myeloid leukemias.

Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that approximately 20% exhibited large regions of homozygosity that could not be accounted for by visible chromosomal abnormalities in the karyotype. Further analysis confirmed that these patterns were due to partial uniparental disomy (UPD). Remission bone marrow was available from five patients showing UPD in their leukemias, and in all cases the homozygosity was found to be restricted to the leukemic clone. Two examples of UPD11p were shown to be of different parental origin as indicated by the methylation pattern of the H19 gene. Furthermore, a previously identified homozygous mutation in the CEBPA gene coincided with a large-scale UPD on chromosome 19. These cryptic chromosomal abnormalities, which seem to be nonrandom, have the characteristics of somatic recombination events and may define an important new subclass of leukemia.

Acute Disease↗
PubMed2005

Characteristics of replicated single-nucleotide polymorphism genotypes from COGA: Affymetrix and Center for Inherited Disease Research.

Genetic Analysis Workshop 14 provided re-genotyped single-nucleotide polymorphism (SNP) data. Specifically, both Center for Inherited Disease Research (CIDR) and Affymetrix genotyped the same 11,560 SNPs from the Affymetrix GeneChip Mapping 10K Array marker set on the same 184 individuals from the Collaborative Study on the Genetics of Alcoholism database. While the inconsistency rate between CIDR and Affymetrix (two different genotypes for the same subject) was low (0.2%), the non-replication rate (two different genotypes for the same subject or one identified genotype and one missing genotype) was substantial (9.5%). The missing data could be from no-call regions, which is inconsistent with recent recommendations about the use of no-call regions in association tests. In addition, no-call regions would suggest that the actual inconsistency rate is higher than reported. A high inconsistency rate has significant impact on power in related hypothesis tests. In addition, the data are consistent with assumptions made in a recently proposed likelihood ratio test of association for re-genotyped data.

Alcoholism↗
PubMed2002

Single-nucleotide polymorphism analysis by hybridization protection assay on solid support.

The clinical need for high-throughput typing methods of single-nucleotide polymorphisms (SNPs) has been increasing. Conventional methods do not perform well enough in terms of speed and accuracy to process a large number of samples, as in clinical testing. We report a new DNA microarray method that uses hybridization protection assay (HPA) by acridinium-ester-labeled DNA probes. Probes were immobilized on the bottom of streptavidin-coated microtiter plates by streptavidin-biotin binding. We studied aldehyde dehydrogenase 2 (ALDH2) genotyping using two probes, discriminating A/G polymorphism. We also designed four probes to type the Alzheimer's disease-related gene ApoE, which has three genotypes (ApoE2, 3, and 4) determined by two SNP loci (C/T polymorphism). SNP analysis of the ALDH2 gene or the ApoE gene from human genome samples by solid-phase HPA was successful. Unlike other methods, the microarray by HPA does not require a washing step and can be completed within 30min. It also has advantages in discriminating one-base mismatch in targets. These characteristics make it a good candidate for practical SNP analysis of disease-related genes or drug-metabolizing enzymes in large numbers of samples.

Acridines↗
PubMed2004

[Five single nucleotide polymorphisms of casein kinase I gamma 2 gene in children with familial febrile convulsions].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) of casein kinase I gamma 2 (CSNK1G2) gene and children with familial febrile convulsions. METHODS: The study samples were collected from unrelated Chinese Han population of Hebei province, including a cohort of 53 children with familial febrile convulsions(FC) and a control cohort of 101 individuals. Genotypes of SNPs rs2074882, rs740423, rs2277737, rs4806825, rs1059684 were typed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of the five SNPs complied well with the Hardy-Weinberg equilibrium in FC group and normal group. The distribution of genotype and frequencies of alleles of the SNPs rs740423, rs2277737, rs1059684 in familial febrile convulsions group was significantly different from that in control group. No significant difference was observed in the distribution of genotypes and frequencies of alleles at SNP rs2074882 between two groups. Analysis on rs4806825 was not made owing to its less allele frequency. CONCLUSION: These data indicate that SNPs rs740423, rs2277737, rs1059684 of CSNK1G2 gene may contribute to familial febrile convulsions in children.

Casein Kinase I↗
PubMed2005

[Study on single nucleotide polymorphism of beta2 adrenoceptor gene in patients with pregnancy induced hypertension of northern China].

OBJECTIVE: To study the association of single nucleotide polymorphism (SNP) at locus +46 of human beta(2)-adrenoceptor (beta(2)-AR) gene with pregnancy induced hypertension (PIH) in women from northern China. METHOD: One hundred and eight women with PIH (PIH group) and ninety seven normal pregnant women (control group) were selected. SNP at locus +46 of human beta(2)-AR was genotyped using PCR-based restriction fragment length polymorphism (RFLP) method. RESULTS: (1) The frequencies of AA, AG and GG genotypes beta(2)-AR at locus +46 were 24.1%, 25.0% and 50.9% in PIH group, respectively. They were 24.7%, 29.9%, and 45.4% in control group, respectively (P > 0.05). The frequencies of the two alleles A and G were 36.6%, 63.4% in PIH group, and 39.7% and 60.3% in control group, respectively (P > 0.05). (2) There was a significant difference in the distribution frequency of beta(2)-AR at locus +46 between mild, moderate and severe degrees of PIH (P < 0.05). CONCLUSION: It indicates that, SNP at locus +46 of beta(2)-AR gene is not associated with generation of PIH in northern China, but it has an association with the severity of PIH.

Adult↗
PubMed2005

Touchdown thermocycling program enables a robust single nucleotide polymorphism typing method based on allele-specific real-time polymerase chain reaction.

Different methods have been developed for single nucleotide polymorphism (SNP) typing during recent years. Allele-specific polymerase chain reaction (ASPCR) is a cost-saving method that scores SNPs by difference of the PCR efficiency of allele-specific primers. However, ASPCR for SNP typing is notoriously confounded for its locus-specific unpredictability and the laborious gel electrophoresis. In the current study, we investigated the real-time kinetics of ASPCR and found that a simple touchdown thermocycling protocol improved its specificity significantly. Combined with real-time PCR, we developed a homogeneous genotyping method and scored more than 1000 genotypes, including all transition and transversion SNPs. A clear genotyping result was identified and validated the robustness of the method. Optimization of reactions and intrinsic modification of allele-specific primers, a laborious process but one that is repeatedly reported to be inevitable for successful ASPCR, was proved to be unnecessary with our method. Accuracy was confirmed with mass spectrometry. These characters enabled real-time ASPCR with the touchdown thermocycling protocol being very competitive among various SNP typing methods for large-scale genetic studies.

Alleles↗
PubMed2000

A coalescent approach to study linkage disequilibrium between single-nucleotide polymorphisms.

We present the results of extensive simulations that emulate the development and distribution of linkage disequilibrium (LD) between single-nucleotide polymorphisms (SNPs) and a gene locus that is phenotypically stratified into two classes (disease phenotype and wild-type phenotype). Our approach, based on coalescence theory, allows an explicit modeling of the demographic history of the population without conditioning on the age of the mutation, and serves as an efficient tool to carry out simulations. More specifically, we compare the influence that a constant population size or an exponentially growing population has on the amount of LD. These results indicate that attempts to locate single disease genes are most likely successful in small and constant populations. On the other hand, if we consider an exponentially growing population that started to expand from an initially constant population of reasonable size, then our simulations indicate a lower success rate. The power to detect association is enhanced if haplotypes constructed from several SNPs are used as markers. The versatility of the coalescence approach also allows the analysis of other relevant factors that influence the chances that a disease gene will be located. We show that several alleles leading to the same disease have no substantial influence on the amount of LD, as long as the differences between the disease-causing alleles are confined to the same region of the gene locus and as long as each allele occurs in an appreciable frequency. Our simulations indicate that mapping of less-frequent diseases is more likely to be successful. Moreover, we show that successful attempts to map complex diseases depend crucially on the phenotype-genotype correlations of all alleles at the disease locus. An analysis of lipoprotein lipase data indicates that our simulations capture the major features of LD occurring in biological data.

Alleles↗
PubMed2006

Multiplex single nucleotide polymorphism genotyping by adapter ligation-mediated allele-specific amplification.

An improved approach for increasing the multiplex level of single nucleotide polymorphism (SNP) typing by adapter ligation-mediated allele-specific amplification (ALM-ASA) has been developed. Based on an adapter ligation, each reaction requires n allele-specific primers plus an adapter-specific primer that is common for all SNPs. Thus, only n+1 primers are used for an n-plex PCR amplification. The specificity of ALM-ASA was increased by a special design of the adapter structure and PCR suppression. Given that the genetic polymorphisms in the liver enzyme cytochrome P450 CYP2D6 (debrisoquine 4-hydroxylase) have profound effects on responses of individuals to a particular drug, we selected 17 SNPs in the CYP2D6 gene as an example for the multiplex SNP typing. Without extensive optimization, we successfully typed 17-plex SNPs in the CYP2D6 gene by ALM-ASA. The results for genotyping 70 different genome samples by the 17-plex ALM-ASA were completely consistent with those obtained by both Sanger's sequencing and PCR restriction fragment length polymorphism (PCR-RFLP) analysis. ALM-ASA is a potential method for SNP typing at an ultra-low cost because of a high multiplex level and a simple optimization step for PCR. High-throughput SNP typing could be readily realized by coupling ALM-ASA with a well-developed automation device for sample processing.

Alleles↗
PubMed2000

An analytic solution to single nucleotide polymorphism error-detection rates in nuclear families: implications for study design.

Recently, there has been increased interest in using Single Nucleotide Polymorphisms (SNPs) as a method for detecting genes for complex traits. SNPs are diallelic markers that have the potential to be inexpensively produced using chip technology. It has been suggested that SNPs will be beneficial in study designs that utilize trio data (father, mother, child). In our previous work, we calculated the probability of detecting Mendelian errors at a SNP locus for a trio randomly selected from a population in Hardy-Weinberg equilibrium. The highest error-detection rate was 30%. Here we investigate the error-detection rate when additional sibs are genotyped. We define an error to be a change from a 1 allele to a 2 allele, or vice versa. Typing one additional sib increases the detection rate on average by 10-13%. Typing two additional sibs increases the detection rate on average by 14-19%. The increase in the detection rate is dependent on the allele frequencies. Equal allele frequencies produce the lowest detection rates, independent of true error rates and number of offspring genotyped. Typing additional siblings not only improves error-detection rates, but can also provide additional linkage information. In order to increase linkage information and error-detection rates, at least two additional siblings should be ascertained when available.

Alleles↗
PubMed2000

Single nucleotide polymorphisms in the coding regions of human CXC-chemokine receptors CXCR1, CXCR2 and CXCR3.

Chemokines and their receptors have critical roles in inflammatory and immunological responses, and thus their genetic contribution to various human disorders needs investigation. In this study, systematic variation screening of the entire coding regions of CXCR1 (IL8RA), CXCR2 (IL8RB) and CXCR3 was carried out, using genomic DNA from a large number of Japanese healthy individuals and patients with rheumatic diseases. In addition to the previously reported variations in CXCR1 and in CXCR2, two non-synonymous, two synonymous substitutions and one nonsense mutation of CXCR1, one non-synonymous and two synonymous substitutions of CXCR2, two non-synonymous substitutions of CXCR3 were newly identified. The common single nucleotide polymorphisms (SNPs) at CXCR1 codon 827 and CXCR2 codon 786 were in strong linkage disequilibrium. In addition, familial analysis indicated that human CXCR3 is located on chromosome X. No significant association was observed between the variations and the tested rheumatic diseases. However, CXCR variations identified in this study will provide valuable information for the future studies in medical sciences as well as in human genetics.

Alleles↗
PubMed2002

Determination of the factor V Leiden single-nucleotide polymorphism in a commercial clinical laboratory by use of NanoChip microelectronic array technology.

BACKGROUND: Methods for analysis of the single-nucleotide polymorphism (SNP) known as factor V Leiden (FVL) are described. The technique provides rapid, highly accurate detection of the point mutation that encodes for replacement of arginine-506 with glutamine. After formal assay qualification, 758 clinical samples that had previously been analyzed by the Invader Monoplex Assay were tested as research samples in a commercial clinical laboratory. METHODS: Primers specific for factor V (FV) were prepared, and PCR was performed. Samples were analyzed using the NanoChip Molecular Biology Workstation with fluorescently labeled reporters for wild-type and SNP sequences. RESULTS: Of the 635 samples classified by the Third Wave assay as FV wild type, 10 were identified as heterozygous FVL by the NanoChip technique. Similarly, of the 114 putative heterozygous samples, 4 were wild type, and of the 9 reported homozygous samples, 6 were homozygous, 2 were heterozygous, and 1 was FV wild type by the NanoChip assay. All 17 results that were discordant with the Third Wave analysis were confirmed by DNA sequencing to be correctly classified by the NanoChip technology. The Nanochip system was 100% accurate in characterizing wild-type, heterozygous, and homozygous samples compared with accuracies of 99.2%, 90.2%, and 100% for the comparable Third Wave analysis. CONCLUSIONS: The NanoChip microelectronic chip array technology is an accurate and convenient method for FVL screening of research samples in a clinical laboratory environment.

Autoanalysis↗
PubMed2004

Effects of single nucleotide polymorphisms in the RANTES promoter region in healthy and HIV-infected indigenous Chinese.

We determined the occurrence of the single nucleotide polymorphisms (SNPs) -403A/G and -28C/G in the promoter region of RANTES in 1082 Chinese blood donors from northern and southern China and 249 HIV patients from southern China. Compared to healthy adults, Chinese AIDS patients had a significantly higher frequency of the -403G allele and haplotype I, -403G/-28C (P < 0.05), and a lower frequency of the -403A/A genotype (P < 0.01). Symptomatic patients had a higher frequency of the -28G allele and a lower frequency of the -28C/C genotype (P < or = 0.01). The plasma RANTES level was significantly lower in blood donors homozygous for haplotype I than in those who were homozygous for haplotypes II and III (P < 0.05). The frequency of the -403G allele was found to be higher in Chinese than in indigenous Africans, but lower than in Caucasians, Hispanics, and African Americans. The frequency of the -28G allele was comparable in Chinese and Japanese; this allele is rare in other ethnic groups. Results suggest that -403G may be associated with increased susceptibility to HIV infection, while -28G may be associated with advanced disease progression. The impact of SNPs on HIV infection appears to be unique in Chinese.

Chemokine CCL5↗