SEARCH · Search PubMed

Results for “nucleotide polymorphism patterns”

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.

SourceResearch connectionFrom yearThrough year

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

At least 1,693 records · Page 94Linked to original sources

PubMed2003

Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3).

The extraneuronal monoamine transporter EMT (HGNC Nomenclature SLC22A3) is the molecular correlate of the classical uptake(2) system responsible for the non-neuronal inactivation of circulating and centrally released catecholamines. Because of its functional profile and expression pattern, EMT is regarded as a candidate gene for diseases related to the sympathetic nervous system and neuropsychiatric disorders. We describe the first investigation of the genetic variability of the EMT gene in human. Six single-nucleotide substitutions and one deletion were detected within the assumed core promoter, the exonic and flanking intronic sequences and the 3'-untranslated region in 100 Caucasian individuals. No amino acid changes were found and Tajima's D was positive (D=2.91; P<0.01). However, the synonymous nucleotide substitution 1233G-->A might serve as a cryptic splice acceptor site. Analysis of linkage disequilibrium between polymorphisms yielded 12 possible haplotypes accounting for more than 90% of all haplotypes. Knowledge of the sequence variation and frequency of the underlying polymorphisms in this member of the amphiphilic solute facilitator family of transporters provides the basis for subsequent association studies and candidate gene approaches.

Genetic Variation↗

PubMed1999

Sequence variation of ribosomal internal transcribed spacers (ITS) in commercially important Phytoseiidae mites.

Preliminary work is needed to assess the usefulness of different markers at different taxonomic scales when a new group is analyzed, such as the commercially important Phytoseiidae mites. We investigate here the level of sequence variation of the nuclear ribosomal spacers ITS 1 and 2 and the 5.8S gene in six species of Phytoseiidae: Neoseiulus culifornicus, N. fallacis, Euseius concordis, Metaseiulus occidentalis, Typhlodromus pyri and Phytoseiulus persimilis. As expected, the 5.8S gene (148 base pairs) is markedly conserved and displays little variation in between genera comparisons. ITS1 and ITS2 show contrasting patterns: while the ITS2 is short (80-89 bp) and shows little variation, the ITS1 is longer (303-404 bp) and is very variable in sequence. This fact compromises reliable nucleotide homologies when comparing the genera. The comparison of ITS1 sequence similarity at the species level might be useful for species identification, however, the value of ITS in taxonomic studies does not extend to the level of the family. The intraspecific variations of ITS were investigated in three species: N. californicus, N. fallacis and E. concordis. The first species has identical ITS1 sequences and the last two display low polymorphism (2 nucleotide substitutions). The ITS2 and 5.8S sequences were identical in all three subspecies comparisons.

Animal Husbandry↗

PubMed1990

DNA recombination and natural selection pressure sustain genetic sequence diversity of the feline MHC class I genes.

Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. These include: (a) a gradual accumulation of spontaneous mutational substitution over evolutionary time; (b) selection against mutational divergence in regions of the class I molecule involved in T cell receptor interaction and also in certain regions that interact with common features of antigens; (c) positive selection pressure in favor of persistence of polymorphism and heterozygosity at 57 nucleotide residues that comprise the antigen recognition site; and (d) periodic intragenic (interallelic) and intergenic recombination within the class I genes. We describe a highly conserved 23-bp nucleotide sequence within the coding region of the first alpha-helix that separates two relatively polymorphic segments located in the alpha 1 domain that may act as a template or "hot spot" for homologous recombination between class I alleles.

Amino Acid Sequence↗

PubMed2006

The role of the testis-specific gene hTAF7L in the aetiology of male infertility.

The X-linked TAF7L gene is homologous to the autosomal transcription factor TAF7. Together with its testis-specific expression pattern, this might point to an important function in spermatogenesis. In order to analyse the involvement of the hTAF7L gene in the aetiology of male infertility, a total of 25 patients with maturation arrest of spermatogenesis have been analysed for the presence of mutations in this gene. Four alterations of the nucleotide sequence, with concomitant changes in the amino acid sequence, have been observed in 12 patients. All sequence alterations were also found either in a control group consisting of men with proven fertility or in a control group with men with normal spermatogenesis. Therefore, these alterations are probably polymorphisms.

Amino Acid Sequence↗

PubMed1999

Incongruence in the diploid B-genome species complex of Glycine (Leguminosae) revisited: histone H3-D alleles versus chloroplast haplotypes.

Variation at the single-copy nuclear locus histone H3-D was surveyed in the diploid B-genome group of Glycine subgenus Glycine (Leguminosae: Papilionoideae), which comprises three named Australian species and a number of distinct but as yet not formally recognized taxa. A total of 23 alleles was identified in the 44 accessions surveyed. Only one individual was clearly heterozygous, which is not surprising given the largely autogamous breeding system of subgenus Glycine. Alleles differed by as many as 19 nucleotide substitutions, nearly all in the three introns; length variation was minimal. Phylogenetic analysis identified two shortest allele trees with very little homoplasy, suggesting that recombination has been rare. Both topological and data set incongruence were statistically significant between histone H3-D allele trees and trees inferred from chloroplast DNA haplotypes previously described from these same accessions. Whereas the distribution of H3-D alleles agrees well with morphologically based taxonomic groupings, chloroplast DNA haplotype polymorphisms transgress species boundaries, suggesting that the chloroplast genome is not tracking taxic relationships. Divergences among chloroplast DNA haplotypes involved in such transgressive patterns appear to be more recent than speciation events, suggesting hybridization rather than lineage sorting.

Alleles↗

PubMed2001

The organic anion transporter family: from physiology to ontogeny and the clinic.

The organic anion transporter (OAT) family handles a wide variety of clinically important compounds (antibiotics, nonsteriodal anti-inflammatory drugs, etc.) and toxins. However, little is known about their appearance during development despite documented differences in the handling of anionic drugs among neonates, children, and adults. A similar spatiotemporal pattern of mRNA expression of the OATs (OAT1-4) during kidney development suggests that OAT genes may be useful in understanding the mechanisms of proximal tubule maturation. Moreover, OAT expression in unexpected extrarenal sites (e.g., spinal cord, bone, skin) has also been detected during development, possibly indicating a role for these transporters in the formation or preservation of extrarenal tissues. The cloning of these transporters also paves the way for computer-based modeling of drug-transporter interactions at the molecular level, potentially aiding in the design and assessment of new drugs. Additionally, increased understanding of single nucleotide polymorphisms in OATs and other transporters may eventually allow the use of a patient's expression profile and polymorphisms to individualize drug therapy.

Animals↗

PubMed2002

The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads.

Mutations in the guanine nucleotide binding alpha-subunit 1 gene (GNAS1) cause Albright's hereditary osteodistrophy, and the parent of transmission determines variable phenotypic expression of the disease. This has suggested that GNAS1 may be under tissue-specific imprinting control, although studies so far available have failed to clearly define the pattern of GNAS1 expression in humans. To establish if GNAS1 is imprinted in human endocrine tissues, we selected 14 thyroid, 10 granulosa cell, 13 pituitary (3 normal glands, 7 GH-secreting adenomas, and 3 nonfunctioning adenomas), 3 adrenal, and 11 lymphocyte samples shown to be heterozygous for a known polymorphism in exon 5. RNA from these tissues was analyzed by RT-PCR, and expression from both parental alleles was evaluated by enzymatic digestion and subsequent quantification of the resulting fragments. The parental origin of Gs alpha was assessed by evaluating neuroendocrine secretory protein 55 and extra large alphas-like protein transcripts, which have been shown to be monoallelically and parent-specifically expressed from the maternal and paternal allele, respectively. By this approach, the great majority of thyroid (n = 12), ovarian (n = 7), and pituitary (n = 11) samples showed an almost exclusive or significantly predominant expression of the maternal allele over the paternal one, whereas in lymphocyte and adrenal samples both alleles were equally expressed. Our results provide evidence for a predominant maternal origin of GNAS1 transcripts in different human adult endocrine tissues, particularly thyroid, ovary, and pituitary, and strongly suggest that this mechanism may play a crucial role in the determination of the phenotypic expression of Albright's hereditary osteodistrophy.

Adenoma↗

PubMed2005

The patterns of natural variation in human genes.

Currently, more than 10 million DNA sequence variations have been uncovered in the human genome. The most detailed variation discovery efforts have focused on candidate genes involved in cardiovascular disease or in susceptibilities associated with exposure to environmental agents. Here we provide an overview of natural genetic variation from the literature and in 510 human candidate genes resequenced for variation discovery. The average human gene contains 126 biallelic polymorphisms, 46 of which are common (> or =5% minor allele frequency) and 5 of which are found in coding regions. Using this complete picture of genetic diversity, we explore conservation, signatures of selection, and historical recombination to mine information useful for candidate gene association studies. In general, we find that the patterns of human gene variation suggest that no one approach will be appropriate for genetic association studies across all genes. Therefore, many different approaches may be required to identify the elusive genotypes associated with common human phenotypes.

Algorithms↗

PubMed2002

Diversification of olfactory receptor genes in the Japanese medaka fish, Oryzias latipes.

Vertebrate olfactory receptors (OR) exists as the largest multigene family, scattered throughout the genome in clusters. Studies have shown that different animals possess remarkably diverse set of OR genes to recognize diverse odor molecules. In order to examine the evolutionary process of OR diversification, we examined three OR gene subfamilies from Japanese medaka fish (seven lines sampled from four populations). For each subfamily, the sequences of ancestral genes were inferred based on distance method. Examination of d(N)/d(S) ratios for each branch of phylogenetic trees suggested that purifying selection is the major force of evolution in medaka OR genes. However, for the mfOR1 and mfOR2 paralogous gene pairs, a nonrandom distribution of fixed amino acid changes and the d(N)>d(S) in a branch suggested that diversifying selection occurred after gene duplication. The fixed amino acid changes were observed in the third, fifth and sixth transmembrane domains, which has been predicted to serve as a ligand-binding pocket in a structural model. Compatibility test suggested that interlocus recombinations involving the fourth transmembrane domain occurred between the mfOR1 and mfOR2 gene pairs. The pattern of nucleotide substitutions in other OR genes agrees with the hypothesis that a limited number of amino acid residues are involved in odorant binding. Such comparative analyses of paralogous OR genes should provide bases for understanding the evolution, the structure, and the functional specificity of OR genes.

Amino Acid Sequence↗

PubMed2001

Very large long-term effective population size in the virulent human malaria parasite Plasmodium falciparum.

It has been proposed that the virulent human malaria parasite Plasmodium falciparum underwent a recent severe population bottleneck. In order to test this hypothesis, we estimated the effective population size of this species from the patterns of nucleotide substitution at 23 nuclear protein-coding loci, using a variety of methods based on coalescent theory. Both simple methods and phylogenetically based maximum-likelihood methods yielded the conclusion that the effective population size of this species has been of the order of at least 10(5) for the past 300,000-400,000 years.

Alleles↗

PubMed2026

Genomic characterization of KPC-2 and NDM coproducing carbapenem-resistant Klebsiella pneumoniae in a hospital: discovery of ST1869 clone and a novel hybrid plasmid.

UNLABELLED: To characterize the plasmid architecture and molecular background of KPC-NDM coproducing carbapenem-resistant Klebsiella pneumoniae (KN-CRKP) in a South China hospital. Five KN-CRKP isolates were collected, including three from one patient. All underwent Illumina sequencing; two (ST11 and ST1869) additionally had Nanopore sequencing. Antimicrobial susceptibility testing strain sequence types, conjugation assays, resistance gene profiling, plasmid typing, genetic structure comparison, core-genome single nucleotide polymorphisms (SNPs) analysis, and plasmid clustering were performed. All isolates exhibited an imipenem minimum inhibitory concentration (MIC) of ≥128 µg/mL and harbored multiple resistance genes. One isolate (1/5) belonged to ST1869 and co-harbored blaKPC-2 and blaNDM-5. The blaNDM-5-carrying plasmid was a novel IncI1/X3 fusion plasmid that also carried blaCMY-42. Unlike several IncX3 plasmids carrying blaNDM in publicly available KN-CRKP genomes from South China, this IncI1/X3 hybrid lacked a complete conjugative transfer system. ST11 was the predominant clone (4/5), co-harboring blaKPC-2 and blaNDM-1. A rare genetic structure, ΔISKpn6-blaKPC-2-ISKpn28, was identified on IncFII plasmids carrying blaKPC-2. Plasmid clustering analysis of 126 comparative KN-CRKP genomes showed diverse sequence types and plasmid backgrounds associated with the KPC/NDM co-production pattern. The observed plasmid diversity and structural variation in KN-CRKP support continued genomic surveillance, with particular attention to the ST1869 clone, the novel IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare "ΔISKpn6-blaKPC-2-ISKpn28" genetic structure. Expanded genomic data on KN-CRKP are needed to further elucidate its resistance mechanisms and plasmid evolutionary trajectories. IMPORTANCE: The co-production of KPC and NDM carbapenemases in Klebsiella pneumoniae poses a formidable threat to clinical antimicrobial therapy, as these enzymes confer resistance to virtually all β-lactam agents, including carbapenems. Here, we report novel genomic features of KN-CRKP in South China, including the emergence of the ST1869 clone, a unique IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare ΔISKpn6-blaKPC-2-ISKpn28 genetic structure. These findings substantially expand current understanding of plasmid evolution and resistance gene dissemination in this region. The identification of diverse resistance mechanisms and clonal backgrounds supports enhanced genomic surveillance and infection-control awareness for pan-resistant Enterobacterales.

Plasmids↗

PubMed2001

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

Adult↗

PubMed1994

Differentiation of Nocardia from rapidly growing Mycobacterium species by PCR-RFLP analysis.

The nucleotide sequences from a region of the groEL gene from one Nocardia asteroides and from several species of Mycobacterium were determined and found to be highly homologous. Based on these homologies, we developed a rapid method capable of differentiating between these two genera. The method is based on restriction fragment-length polymorphism (RFLP) analysis of DNA amplified from the groEL gene that is highly conserved between mycobacteria and nocardiae. When the groEL gene from species of these genera is enzymatically amplified by the polymerase chain reaction (PCR), a 422-bp fragment is generated. Correlation of the restriction endonuclease digestion patterns of the amplification products with reference and/or biochemically characterized clinical samples enabled us to establish RFLP profiles for ten species of Mycobacterium and five species of Nocardia. When a portion of the groEL gene from each of these organisms is digested with the restriction endonuclease Hae III, that organism is readily assigned to one of these two genera on the basis of the derived RFLP patterns. The utility of this approach was examined by testing 105 pure cultures from samples previously identified by routine culture techniques for the presence of groEL DNA sequences of mycobacterial or nocardial origin. This analysis correctly identified the organism in all samples tested. In summary, PCR-RFLP analysis provides a rapid and sensitive method for the differentiation of Nocardia species from rapidly growing Mycobacterium species.

Bacterial Proteins↗

PubMed1999

Unusual haplotype structure at the proximal breakpoint of In(2L)t in a natural population of Drosophila melanogaster.

The existence of temporally stable frequency clines for In(2L)t in natural populations of Drosophila melanogaster suggests a role for selection in the maintenance of this polymorphism. We have collected nucleotide polymorphism data from the proximal breakpoint junction regions of In(2L)t to infer its evolutionary history. The finding of a novel LINE-like element near the In(2L)t breakpoint junction in sampled inverted chromosomes supports a transposable element-mediated origin for this inversion. An analysis of nucleotide variation in a Costa Rican population sample of standard and inverted chromosomes indicates a unique and relatively recent origin for In(2L)t. Additional In(2L)t alleles from three geographically diverse populations reveal no detectable geographic differentiation. Low levels of In(2L)t nucleotide polymorphism suggest a recent increase in the inversion's frequency in tropical populations. An unusual feature of our sample of standard alleles is a marked heterogeneity in levels of linkage disequilibrium among polymorphic sites across the breakpoint region. We introduce a test of neutral equilibrium haplotype structure that corrects both for multiple tests and for an arbitrarily chosen window size. It reveals that an approximately 1.4-kb region immediately spanning the breakpoint has fewer haplotypes than expected under the neutral model, given the expected level of recombination in this genomic region. Certain features of our data suggest that the unusual pattern in standard chromosomes is the product of selection rather than demography.

Animals↗

PubMed2002

Identification and broad dissemination of the CTX-M-14 beta-lactamase in different Escherichia coli strains in the northwest area of Spain.

During the course of a molecular epidemiology study of mechanisms of antibiotic resistance in the area served by our hospital (516,000 inhabitants), we isolated the gene encoding CTX-M-14 beta-lactamase. Thirty clinical strains (27 Escherichia coli and 3 Klebsiella pneumoniae isolates) with a phenotype of extended-spectrum beta-lactamase were collected from January to October 2001 and studied for the presence of the CTX-M-14 beta- lactamase gene. By isoelectric point determination, PCR, and nucleotide sequencing, we detected the presence of this gene in 17 E. coli strains belonging to 15 different genotypes (REP-PCR) causing infections in 17 different patients. Epidemiological studies based on medical records did not suggest any relationship between the patients infected with these E. coli strains and, interestingly, 7 of 30 patients harboring strains with extended-spectrum beta-lactamases never had contact with the hospital environment before the clinical E. coli isolation. Conjugation experiments revealed that this gene was plasmid mediated in the 17 E. coli strains, and plasmid restriction fragment length polymorphisms showed 9 different patterns in the 17 E. coli strains. By PCR, the sequence of the tnpA transposase gene of the insert sequence ISEcp-1 was detected in all the plasmids harboring the CTX-M-14 gene. These results strongly suggest that plasmid dissemination between different E. coli strains in addition to a mobile element (transposon) around the beta-lactamase gene may be involved in the spreading of the CTX-M-14 gene. This study reinforces the hypothesis that the epidemiology of the prevalence of the beta-lactamase genes is changing and should alert the medical community to the increase in the emergence of the CTX-M beta-lactamases worldwide.

Adolescent↗

PubMed2004

Allelic polymorphism in the ovine DQA1 gene.

Variation in the ovine DQA1 gene was investigated by amplification of exon 2 using PCR, followed by single-strand conformational polymorphism (SSCP) analysis, cloning, and DNA sequencing. Fourteen novel SSCP patterns, representing 14 different sequences, were identified. Eight of these 14 sequences were identical to published DQA1 sequences from sheep, whereas the remaining six were novel but similar to the published DQA1 sequences from sheep and cattle. These six new sequences exhibited conserved region and variable region patterns similar to the published sheep DQA1 sequences, but were different than the published DQA2 sequences from sheep. All of these 14 putative sheep DQA1 sequences fulfilled the criteria used by the established bovine leukocyte antigens major histocompatibility complex nomenclature committee for assignment as new alleles. Comparison of the available DQA1 sequences from sheep and cattle revealed several clusters of ovine DQA1 sequences, and some sheep alleles were more similar to cattle alleles than other sheep alleles. The occurrence of trans-species polymorphism suggests the action of balancing selection at the DQA1 locus. Twenty-four percent of the nucleotide positions showed variation within exon 2, and this variation seems to have arisen largely by point mutation and gene conversion. The nonsynonymous and synonymous substitution rates were similar in both the putative antigen-binding site codons and the putative nonantigen-binding site codons. The extensive polymorphism reported in this article is consistent with polymorphism reported at the bovine DQA1 locus.

Alleles↗

PubMed1991

Molecular fingerprinting of isolates of the genus Peptostreptococcus using rRNA genes from Escherichia coli and P. anaerobius.

Restriction fragment length polymorphisms (RFLPs) of rRNA genes were evaluated as a tool for intra- and interspecies differentiation of Peptostreptococcus isolates. RFLPs from a collection of 20 clinical isolates and five ATCC strains representing five Peptostreptococcus spp. (P. anaerobius, P. asaccharolyticus, P. magnus, P. micros and P. prevotii) were obtained by hybridization of Southern blots of HindIII- or EcoRI-digested genomic DNA with three probes: probe A, a 0.98 kb HindIII fragment with a partial 16S rRNA gene sequence from P. anaerobius ATCC 27337; probe B, cloned Escherichia coli rrnB operon in plasmid pKK3535; and probe C, E. coli 16S and 23S rRNA. The hybridization patterns varied, but all yielded RFLPs useful for both intra- and inter-species differentiation. RFLPs of P. asaccharolyticus clinical isolates were closely related to each other and differed significantly from those of the ATCC type strains. The profiles of P. prevotii differed from those of the other four species studied, and based on the HindIII- and EcoRI-generated RFLPs, the strains in this species are more heterogeneous than the other four species studied.

Cloning, Molecular↗

PubMed2005

MGMT genotype modulates the associations between cigarette smoking, dietary antioxidants and breast cancer risk.

O(6)-methylguanine DNA methyl-transferase (MGMT) is the only known critical gene involved in cellular defense against alkylating agents in the DNA direct reversal repair (DRR) pathway. Three single nucleotide polymorphism (SNP) coding for non-conservative amino acid substitutions have been identified [C250T (Leu84Phe), A427G (Ile143Val) and A533G (Lys178Arg)]. To examine the importance of the DRR pathway in risk for breast cancer and the potential interaction with cigarette smoking and dietary antioxidants, we genotyped for these variants using biospecimens from the Long Island Breast Cancer Study Project. Genotyping was performed by a high throughput assay with fluorescence polarization and included 1067 cases and 1110 controls. Overall, there was no main effect between any variant genotype, haplotype or diplotype and breast cancer risk. Heavy smoking (>31 pack-year) significantly increased breast cancer risk for women with the codon 84 variant T-allele [odds ratio, OR = 3.0, 95% confidence interval (95% CI) = 1.4-6.2]. An inverse association between fruits and vegetables consumption and breast cancer risk was observed among women with the wild-type genotype for codon 84 (OR = 0.8, 95% CI = 0.6-0.9 for > or =35 servings of fruits and vegetables per week and CC genotype versus those with <35 servings per week and CC genotype). The association between fruits and vegetables consumption and reduced breast cancer risk was apparent among women with at least one variant allele for codon 143 (OR = 0.6, 95% CI = 0.5-0.9 for > or =35 servings of fruits and vegetables per week and AG or GG genotype versus those with <35 servings per week and AA genotype). Similar patterns were observed for dietary alpha-carotene and supplemental beta-carotene, but not for supplemental vitamins C and E. These data suggest that polymorphisms in MGMT may modulate the inverse association previously observed between fruits and vegetables consumption, dietary antioxidants and breast cancer risk, and support the importance of fruits and vegetables on breast cancer risk reduction.

Adult↗