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At least 415 records · Page 23Linked to original sources

PubMed2003

Detection of single nucleotide polymorphism (SNP) controlling the waxy character in wheat by using a derived cleaved amplified polymorphic sequence (dCAPS) marker.

We investigated a single nucleotide polymorphism (SNP) in the Wx-D1 gene, which was found in a mutant waxy wheat, and which expressed the Wx-D1 protein (granule-bound starch synthase I) as shown by immunoblot analysis. We also assayed starch synthase activity of granule-bound proteins. Using 22 doubled-haploid (DH) lines and 172 F(5) lines derived from the wild type x the mutant, we detected SNP via a PCR-based (dCAPS) marker. Amplified PCR products from Wx-D1 gene-specific primers, followed by mismatched primers designed for dCAPS analysis, were digested with the appropriate restriction enzyme. The two alleles, and the heterozygote genotype were easily and rapidly discriminated by gel-electrophoresis resolution to reveal SNP. All progeny lines that have the SNP of the mutant allele were waxy. Integrating the results of dCAPS analysis, immunoblot analysis and assays of starch synthase activity of granule-bound proteins indicates that the SNP in the Wx-D1 gene was responsible for its waxy character. This dCAPS marker is therefore useful as a marker to introduce the mutant allele into elite breeding lines.

Alleles↗

PubMed1998

Genetic polymorphism of Leishmania species using kinetoplast DNA restriction fragment length polymorphism and cDNA probe of Leishmania donovani.

Leishmaniasis represents a group of diseases that range from simple cutaneous lesions through metastasizing diffused cutaneous to severe systemic infection depending upon the taxon to which the causative parasite belongs. Therefore, it is important to identify the infecting Leishmania. Methods presently being used, including immunology, biochemistry and molecular biology have one or the other limitations, leaving scope for the search for newer probes. This study reports the characterization of leishmania isolates both by restriction fragment length polymorphism of kinetoplast DNA (kDNA) and genomic DNA. The genomic DNA was probed with a cDNA probe B2a1. Using a kDNA restriction pattern technique, different isolates of Leishmania donovani could be differentiated from the UR6 strain of L. tropica, but it was not possible to differentiate between newer local isolates of L. donovani with most of the restriction enzymes except AluI. However, the B2a1 cDNA probe was able to differentiate these isolates effectively. Both of these techniques could differentiate newer local isolates of L. donovani from the older isolates of L. donovani from India, i.e., DD8, RMRI and SS. The Indian isolates of L. donovani could also be differentiated from isolates of L. donovani from Jeddah and Germany using both techniques. The present study indicates that the cDNA probe B2a1 can be used as an important adjunct to kDNA restriction analysis for the characterization of Leishmania species.

Animals↗

PubMed2004

Convulsive disorder and genetic polymorphism. Association of idiopathic generalized epilepsy with haptoglobin polymorphism.

Haptoglobin is a polymorphic protein that is well known for its hemoglobin (Hb)-binding property. The protein shows gross differences in molecular size among genotypes, resulting in different degrees of diffusion in central nervous system tissue. Since the breakdown of erythrocytes in the intracerebral fluid results in Hb-mediated free OH radical formation, lipid peroxidation, and increased neuronal excitability, a differential diffusion of haptoglobin phenotypes in the intracerebral fluid might result in a different degree of protection from oxidative damage. We have studied two samples of children with idiopathic generalized epilepsy from two different Italian populations. In both samples the haptoglobin *1/*1 genotype is much less represented in epileptic children than in controls. These observations suggest that subjects carrying the Hp*1/*1 genotype, that has the lowest molecular size and diffuses more readily in the interstitial cerebral fluid, are more protected against idiopathic generalized epilepsy than those with other haptoglobin genotypes.

Adult↗

PubMed2006

G-protein beta 3 subunit polymorphism C1429T and low-density lipoprotein receptor-related protein 5 polymorphism A1330V are risk factors for hypercholesterolemia in Japanese males--a prospective study over 5 years.

We examined the relationship between the C825T, C1429T, and A-350G variants in the G-protein beta 3 subunit (GNB3) gene, the A1330V and Q89R variants in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the risk of hypercholesterolemia in a prospective study in Japanese workers. This study included observations over a 5-year period from 1997 to 2002 on 936 males and 662 females who were not hypercholesterolemic on entry. Hypercholesterolemia was defined as a serum total cholesterol level of 240 mg/dL or higher. Pooled logistic regression analyses were performed using either of the gene variants with age, body mass index, smoking, alcohol consumption, and habitual exercise as the covariates. The risk of the development of hypercholesterolemia was 2.27 times higher in males with the TT genotype of GNB3/C1429T than in males with the CC genotype (95% confidence interval, 1.04-4.94), after adjustment for the effects of other potential covariates. Simultaneously, the risk was 1.49 times higher in males with the AV genotype of LRP5/A1330V than in males with the AA genotype (95% confidence interval, 1.04-2.12) after adjustment for the effects of other potential covariates. This study indicates the GNB3/C1429T and LRP5/A1330V are independent risk factors for hypercholesterolemia in Japanese males and suggests that targeting these polymorphisms may be beneficial when attempting to prevent hypercholesterolemia in the general Japanese male population.

Adult↗

PubMed1992

Polymerase chain reaction--amplification of the coding sequence of the type X collagen gene from genomic DNA and identification of a polymorphism that changes Gly to Arg at position 545 by single-strand conformation polymorphism analysis.

Type X collagen is a specific product of hypertrophic growth plate chondrocytes and it has been suggested that mutations in the corresponding gene (COL1OA1) may be responsible for certain heritable disorders affecting growth plate cartilage such as the epiphyseal dysplasias. We have amplified the coding region of COL1OA1 employing polymerase chain reaction (PCR) of genomic DNA. Single-strand conformation polymorphism (SSCP) analysis of PCR products followed by direct sequencing identified a G to C transition that results in a Gly to Arg substitution at position 545 of the polypeptide chain. The sequence variation was confirmed by restriction enzyme analysis with BsaJ 1. Analysis of a family with multiple epiphyseal dysplasia ruled out this sequence change as a cause of the disease. This is the first report showing application of SSCP for detection of a sequence variant in COL1OA1.

Arginine↗

PubMed2003

In polymorphic genomic regions indels cluster with nucleotide polymorphism: Quantum Genomics.

Previously, we have described polymorphic frozen blocks (PFBs) within the Major Histocompatibility Complex (MHC) as regions of several hundred kilobases characterised by high nucleotide diversity, little or no recombination, duplicated segments, disease susceptibility, and human endogenous retroviruses. The nucleotide diversity profile within these PFBs shows peaks and troughs outside of the Class I genes, reflecting other important genes (or sequences) in the region. Here we show that indel density is also clustered with similar peaks and troughs. In fact, SNPs and indels are co-located within PFBs.

Databases, Nucleic Acid↗

PubMed1999

Angiotensin converting enzyme gene insertion/deletion polymorphism, angiotensinogen gene polymorphisms, family history of hypertension, and childhood blood pressure.

Earlier epidemiologic studies have yielded inconsistent results on the extent and timing of the blood pressure (BP) increase in offspring of hypertensive parents. We hypothesized that a familial influence on the BP of the offspring exists from birth on, but becomes significant only later in childhood. We studied the influence of familial occurrence of hypertension on the BP of 3596 children aged 6 to 18 years during a 6-year follow-up. In addition, we examined the possible associations of BP variations with polymorphisms of two candidate genes for hypertension, ie, those coding for the angiotensin converting enzyme (ACE) and those coding for angiotensinogen. A positive family history of hypertension was reflected as the occurrence of higher systolic BP values from the age of 9 years and upward among the females and from the age of 12 years and upward among the males. The mean differences in BP varied from 3.2 to 5.8 mm Hg (systolic) and 2.1 to 5.9 mm Hg (diastolic) between the female offspring of normotensive and hypertensive parents and grandparents. The systolic BP values were significantly higher among females with a hypertensive history in two generations in comparison with females from normotensive families. Among the male offspring of hypertensive and normotensive families, the BP differences were inconsistent. The deletion/deletion males had higher systolic BP values than those with other ACE genotypes. In contrast, variation at the angiotensinogen gene locus was not significantly associated with BP. We conclude that parental history of hypertension is a risk factor for high blood pressure among the offspring from the ages of 9 to 12 years and upward, and hypertension within two generations may enhance this effect. Although the common genetic variation of ACE may influence blood pressure in male children and adolescents, our data do not suggest a role for the common variation of the angiotensinogen gene as a BP regulator during childhood.

Adolescent↗

PubMed2005

Mass spectrometry-based loss of heterozygosity analysis of single-nucleotide polymorphism loci in paraffin embedded tumors using the MassEXTEND assay: single-nucleotide polymorphism loss of heterozygosity analysis of the protein tyrosine phosphatase receptor type J in familial colorectal cancer.

As the number of identified single-nucleotide polymorphisms (SNPs) increases, high-throughput methods are required to characterize the informative loci in large patient series. We investigated the feasibility of MassEXTEND LOH analysis using Sequenom's MassArray RT software, a mass spectrometry method, as an alternative to determine loss of heterozygosity (LOH). For this purpose, we studied the c.827A>C SNP (1176A>C p.Gln276Pro) in protein tyrosine phosphatase receptor type-J (PTPRJ), which is frequently deleted in human cancers. In sporadic colorectal cancer (CRC), c.827A>C showed allele-specific LOH of the c.827A allele, which is important because LOH of PTPRJ may be an early event during sporadic CRC. To elucidate the impact of this low-penetrance gene on familial CRC, we studied c.827A>C in 222 familial CRC cases and 156 controls. In 6.2% of the A/C genotyped CRC samples, LOH of c.827A was observed with MassEXTEND LOH analysis and confirmed by conventional sequencing. Furthermore, a case with LOH of c.827A showed no LOH in 22 synchronously detected adenomas, including one with malignant transformation. The importance of the PTPRJ- c.827A>C SNP appears to be limited in familial CRC. We conclude that MassEXTEND LOH analysis (using Sequenom's MassARRAY RT software) is a sensitive, high-throughput, and cost-effective method to screen SNP loci for LOH in formalin-fixed paraffin-embedded tissue.

Aged↗

PubMed1992

The alcohol dehydrogenase polymorphism in natural populations of Drosophila melanogaster: ADH activity variation restriction site polymorphism and the Adh cline.

Alcohol dehydrogenase activity has been measured in 186 iso-second chromosome lines--104 from seven Australian populations and 82 from six Chinese populations. Restriction endonuclease variation in the Adh gene region in these lines has previously been described (Jiang & Gibson, 1991). The mean ADH activity of AdhF and AdhS lines was significantly higher in the Chinese samples than in the Australian samples. In each population on both continents the mean activity of the AdhF lines is significantly higher than that of the AdhS lines. Six lines homozygous for a thermostability variant, AdhFChD (detected in four of the Chinese populations), had intermediate levels of ADH activity and protein amount. In a subset of the lines with the highest and lowest levels of ADH, there was a correlation of 0.69 between ADH activity and ADH CRM. None of the restriction site variants was consistently associated with the amount of ADH activity. Associations between BamHI (-7.2), the Adh polymorphism and ADH activity suggest that there are modifiers of ADH 5' to the gene. The deletion (0.2) at position -2.8 on the restriction map (Jiang & Gibson, 1991) was associated with increased levels of ADH activity in AdhS lines from China. Two unique insertions in the gene region were associated with low activity in AdhF lines and a null activity allele had a deletion removing most of exon 2. A single line with a duplication of a part of the Adh coding region and of the 5' regulatory section had relatively high ADH activity. Considering all the data, the main factor affecting ADH activity levels in populations is the frequency of AdhF.

Alcohol Dehydrogenase↗

PubMed2002

Anorexia nervosa (restrictive subtype) is associated with a polymorphism in the novel norepinephrine transporter gene promoter polymorphic region.

Long-term weight-restored patients with anorexia nervosa (AN) have lower norepinephrine levels than controls. Since this may reflect altered reuptake by the norepinephrine transporter (NET), we hypothesised that the NET gene was involved in the genetic component of AN. PCR-amplification of an AAGG repeat island (AAGG1) in the NET gene promoter region revealed a novel 343-bp sequence with five additional AAGG repeat islands (AAGG2-AAGG6). We named the sequence from AAGG1 to AAGG6 inclusive, the NET gene promoter polymorphic region (NETpPR). A 4-bp deletion (S4) or insertion (L4) in AAGG4 resulted in the net loss or gain, respectively, of a putative Elk-1 transcription factor site. The transmission disequilibrium test(TDT) with 87 Australian trios (patient plus parents) demonstrated significant preferential transmission of L4 (McNemar's chi(2) = 7.806, df = 1, P = 0.0052, odds ratio: 2.1) from parent to child with restricting AN (AN-R), suggesting that L4 or a DNA variant in linkage disequilibrium with it, doubles the risk for developing AN-R.

Adolescent↗

PubMed1998

Random amplified polymorphic DNA and amplified ribosomal DNA spacer polymorphism: powerful methods to differentiate Streptococcus thermophilus strains.

Streptococci from different collections and dairy materials were characterized by conventional and molecular methods. After amplification of the 16S-23S rDNA spacer region, all the strains referable to the genus Streptococcus exhibited a single polymerase chain reaction (PCR) product, allowing their differentiation from enterococci. Cleaving this PCR product with Hae III, two different restriction patterns could be observed, allowing Streptococcus salivarius DSM 20560T, Strep. thermophilus NCDO 822 and two strains of Streptococcus spp. to be gathered in one group and all the other strains in another. In order to achieve strain typing, all the cultures were investigated by random amplified polymorphic DNA (RAPD)-PCR analysis employing two selected primers. The results were treated by cluster analysis, appearing significantly consistent with both the taxonomic position and the origin of the strains. Pulsed-field gel electrophoresis (PFGE) of Sma I digests of the genomic DNA from 11 representative strains with decreasing levels of RAPD similarity allowed their diversity to be confirmed, even though RAPD-PCR proved to be less discriminating than PFGE analysis. The results are discussed with reference to the capability of the analytical procedures used to aid both identification and strain typing of streptococci, as well as the taxonomic structure of the species Strep. thermophilus.

Bacterial Typing Techniques↗

PubMed2000

Rapid detection of dihydropteroate polymorphism in AIDS-related Pneumocystis carinii pneumonia by restriction fragment length polymorphism.

Sulpha agents, which act by inhibiting the enzyme dihydropteroate synthase (DHPS), are used widely for the treatment and prophylaxis of Pneumocystis carinii pneumonia (PCP). Recently, we have shown that mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis carinii f.sp hominis are associated with failure of sulpha prophylaxis and increased mortality in HIV-1 positive patients with PCP, suggesting that DHPS mutations may cause sulpha resistance. To facilitate detection of DHPS mutations we developed a restriction fragment length polymorphism (RFLP) assay, detecting mutations at codon 55 and 57 of the P. carinii DHPS gene. The RFLP-assay was compared with direct DNA sequencing on 27 PCP isolates from HIV-1 positive patients with a mixture of wildtype and mutant DHPS types. In all samples the RFLP-assay correctly identified wildtype or DHPS mutation at codon 55 or 57. Combined with DNA extraction by a Chelex-based method, this method can be performed within 1 d and allows a fast, cost-efficient and reliable method of detection of DHPS mutations in P. carinii.

AIDS-Related Opportunistic Infections↗

PubMed1998

Point mutation of a rubella virus E1 protein T-cell epitope by substitution of single amino acid reversed the restrictive HLA-DR polymorphism: a possible mechanism maintaining HLA polymorphism.

The influence of single amino acid substitutions within a rubella E1 protein T-cell epitope, E1(273-284) on T-cell recognition was studied. Substitutions of an uncharged amino acid A for an E or for a T and substitution of a T for S were found to not significantly reduce the T-cell responses. However, substitution of a charged residue such as E for hydrophobic residues (I, V, or W); D for Q; or a relatively larger size amino acid for polar residues completely abolished the cytotoxicities mediated by E1(273-284)-specific T-cell clone. A set of single amino acid-substituted peptide analogs of E1(273-284) not eliciting cytotoxicity of the T-cell clone was used to test the influence of point mutation of the epitope on HLA DR restrictions. A panel of B-cell lines with different DR4 subtypes was used as targets in cytotoxicity assays to determine the restrictive HLA molecules. Results showed that modification of the T-cell epitope by point mutation could reverse the HLA DR restriction from one allele to other alleles. A model based on these results has been proposed to explain the mechanism balancing major histocompatibility complex (MHC) polymorphism in outbred populations.

Amino Acid Substitution↗

PubMed2000

Toward a physical map of Drosophila buzzatii. Use of randomly amplified polymorphic dna polymorphisms and sequence-tagged site landmarks.

We present a physical map based on RAPD polymorphic fragments and sequence-tagged sites (STSs) for the repleta group species Drosophila buzzatii. One hundred forty-four RAPD markers have been used as probes for in situ hybridization to the polytene chromosomes, and positive results allowing the precise localization of 108 RAPDs were obtained. Of these, 73 behave as effectively unique markers for physical map construction, and in 9 additional cases the probes gave two hybridization signals, each on a different chromosome. Most markers (68%) are located on chromosomes 2 and 4, which partially agree with previous estimates on the distribution of genetic variation over chromosomes. One RAPD maps close to the proximal breakpoint of inversion 2z(3) but is not included within the inverted fragment. However, it was possible to conclude from this RAPD that the distal breakpoint of 2z(3) had previously been wrongly assigned. A total of 39 cytologically mapped RAPDs were converted to STSs and yielded an aggregate sequence of 28,431 bp. Thirty-six RAPDs (25%) did not produce any detectable hybridization signal, and we obtained the DNA sequence from three of them. Further prospects toward obtaining a more developed genetic map than the one currently available for D. buzzatii are discussed.

Amino Acid Sequence↗

PubMed1989

Polymorphism of the human T cell receptor alpha chain variable genes: identification of a highly polymorphic V gene probe.

In this study, we report the RFLP of the human T cell receptor (TCR) alpha chain variable gene segments. Using DNA samples from 20 individuals and three restriction endonucleases (BamHI, EcoRI and HindIII), the degree of RFLP of a number of different V gene segments was defined. Half of the V alpha subfamilies (6/12) were characterized by a predominant hybridization pattern, with only a few individuals displaying a second pattern. However, one particular V gene family, V alpha 6, has at least five allelic forms that segregated consistently in familial studies. The V alpha polymorphisms revealed in this study, together with those exhibited by V beta gene subfamilies, should prove useful in studying possible associations between TCR gene usage and disorders of the immune system.

Alleles↗

PubMed1995

Isoenzyme, restriction fragment length polymorphism, and random amplified polymorphic DNA characterization of Phaffia rhodozyma Miller et al.

The validity of the species concept was examined with strains of Phaffia rhodozyma by comparing the isoenzyme profiles, ribosomal DNAs, and random amplified polymorphic DNA (RAPD) patterns of the strains. The isoenzyme profiles appeared to be more stable than the RAPD patterns or the electrophoretic karyotypes determined previously (A. Nagy, N. Garamszegi, C. Vágvölgyi, and L. Ferenczy, FEMS Microbiol. Lett., in press). The ribosomal DNA patterns revealed only a limited degree of variability, while RAPD analysis proved to be the most useful method for differentiating the strains studied. Strain CBS 5905T (T = type strain) produced characteristic RAPD patterns, which were different from those produced by the other strains. However, despite the high degree of variability observed, the isoenzyme data and the slightly variable ribosomal DNA hybridization profiles confirmed that the strains which we examined belong to one species.

Base Sequence↗

PubMed2002

Neighboring-nucleotide effects on single nucleotide polymorphisms: a study of 2.6 million polymorphisms across the human genome.

We investigated substitution patterns and neighboring-nucleotide effects for 2,576,903 single nucleotide polymorphisms (SNPs) publicly available through the National Center for Biotechnology Information (NCBI). The proportions of substitutions were A/G, 32.77%; C/T, 32.81%; A/C, 8.98%; G/T, 9.06%; A/T, 7.46%; and C/G, 8.92%. The two nucleotides immediately neighboring the variable site showed major deviation from genome-wide and chromosome-specific expectations, although lesser biases extended as far as 200 bp. On the 5' side, the biases for A, C, G, and T were 1.43%, 4.91%, -1.70%, and -4.62%, respectively. These biases were -4.44%, -1.59%, 5.05%, and 0.99%, respectively, on the 3' side. The neighboring-nucleotide patterns for transitions were dominated by the hypermutability effects of CpG dinucleotides. Transitions were more common than transversions, and the probability of a transversion increased with increasing A + T content at the two adjacent sites. Neighboring-nucleotide biases were not consistent among chromosomes, with Chromosomes 19 and 22 standing out as different from the others. These data provide genome-wide information about the effects of neighboring nucleotides on mutational and evolutionary processes giving rise to contemporary patterns of nucleotide occurrence surrounding SNPs.

Base Composition↗

PubMed1995

Metastable single-strand DNA conformational polymorphism analysis results in enhanced polymorphism detection.

Single-strand DNA conformational polymorphism (SSCP) makes use of sequence-dependent folding of single-stranded DNA (ssDNA), which alters the electrophoretic mobility of the fragments, to detect sequence differences between closely related molecules. In this study ssDNAs were purified by depletion of the complementary strand and PCR reactants on magnetic M-280-strepavidin beads. It was found that SSCP profiles created by purified ssDNAs differ from the profiles created by more usual SSCP methods. Under some conditions, SSCP profiles using whole PCR reaction products may result from the interaction between residual PCR primers and ssDNAs. We observed that the ratio of conformers revealed by band position and band intensity may vary between the assay techniques and misinterpretation of sequence variants may result. Another observation of this study was the formation of metastable conformational isomers with bead-purified ssDNAs by eliminating the thermal treatment used in conventional SSCP methods. The metastable SSCP (mSSCP) represents a novel and sensitive system for detection of sequence variation between closely related DNAs. The technique used here for the preparation of the purified ssDNAs is potentially useful for automated PCR-SSCP analysis using capillary electrophoresis or other methods.

Autoradiography↗