Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “structural variants”

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.

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

At least 1,495 records · Page 83Linked to original sources
PubMedDate not supplied

[Etiological structure of respiratory infections in different variants of acute bronchitis].

The microbiological and virological examination of 87 acute bronchitis patients (36 patients with the prolonged course and 31 patients with the relapsing course of the disease) was carried out. All forms of bronchitis were characterized by a high degree of infection with respiratory viruses and pneumococci. Haemophilus influenzae (type b) infection was registered rather rarely and only in combination with pneumococcal one. The highest characteristics of viro-bacterial associations were found in patients with acute bronchitis and with prolonged form of acute bronchitis, viral associations--with the prolonged and relapsing forms of the course of acute bronchitis in the presence of the bronchoobstructive syndrome.

Acute Disease↗
PubMed1984

Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin.

Gelsolin is an actin-fragmenting cytoplasmic protein. A functionally similar protein has also been identified in plasma. We have compared the structure of the cytoplasmic and plasma forms of gelsolin and examined their biosynthetic relationships. Plasma gelsolin is larger than cytoplasmic gelsolin (Mr 93,000 versus 90,000, respectively) and is more positively charged. Partial amino acid sequencing analyses show that the two gelsolins share a common 29 amino acid sequence which lies at the NH2-terminal end of cytoplasmic gelsolin and spans residues 26-55 of plasma gelsolin. Compared with cytoplasmic gelsolin, plasma gelsolin contains an additional peptide of 25 amino acids at its NH2 terminus. The human hepatoma-derived cell line, HepG2, synthesizes both the 90-kDa and the 93-kDa gelsolins but secretes only the 93-kDa form. Pulse-chase experiments demonstrate that the rate of disappearance of the 93-kDa gelsolin from the cells corresponds with the rate of appearance of the 93-kDa gelsolin in the medium, whereas the rate of disappearance of the 90-kDa gelsolin is independent of and slower than that of the secreted plasma protein. We conclude that cytoplasmic and plasma gelsolins are structurally similar but not identical, that after synthesis these proteins are processed independently, and that the fate of each is distinct.

Amino Acid Sequence↗
PubMed1984

[Variants of movement disorders within the psychopathologic structure of borderline neuropsychiatric diseases in young children].

On the basis of the examination covering 30 young children (aged 2 months to 3.5 years), three variants of motor psychogenic disorders were specified. Group I included elementary, stereotypic motor phenomena expressed as special poses, rocking, jack-knifing, finger sucking and other stereotypes of motor acts. Group II was characterized by more complicated motor and psychomotor disorders in the form of various manifestations of motor infantilism. Group III comprised children with neurotic motor monosymptomatic and ritual-behavioural obsessive actions. The above disorders are assessed from the evolutional-dynamic point of view.

Borderline Personality Disorder↗
PubMed2025

Meta-analysis models with group structure for pleiotropy detection at gene and variant level using summary statistics from multiple datasets.

Genome-wide association studies (GWASs) have highlighted the importance of pleiotropy in human diseases, where one gene can impact 2 or more unrelated traits. Examining shared genetic risk factors across multiple diseases can enhance our understanding of these conditions by pinpointing new genes and biological pathways involved. Furthermore, with an increasing wealth of GWAS summary statistics available to the scientific community, leveraging these findings across multiple phenotypes could unveil novel pleiotropic associations. Existing selection methods examine pleiotropic associations one by one at a scale of either the genetic variant or the gene, and thus cannot consider all the genetic information at the same time. To address this limitation, we propose a new approach called MPSG (Meta-analysis model adapted for Pleiotropy Selection with Group structure). This method performs a penalized multivariate meta-analysis method adapted for pleiotropy and takes into account the group structure information nested in the data to select relevant variants and genes (or pathways) from all the genetic information. To do so, we implemented an alternating direction method of multipliers algorithm. We compared the performance of the method with other benchmark meta-analysis approaches such as GCPBayes, PLACO, and ASSET by considering as inputs different kinds of summary statistics. We provide an application of our method to the identification of potential pleiotropic genes between breast and thyroid cancers.

Humans↗
PubMed2006

Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in Chinese population.

A systematic study on the structure and function of Glucose-6-phosphate dehydrogenase (G6PD) variations was carried out in China. A total of 155,879 participants were screened for G6PD deficiency by the G6PD/6PGD ratio method and 6,683 cases have been found. The prevalence of G6PD deficiency ranged from 0 to 17.4%. With informed consent, 1,004 cases from 11 ethnic-based groups were subjected to molecular analysis. Our results showed the followings: (1) The G6PD variants are consistent across traditional ethnic boundaries, but vary in frequencies across ethnic-based groups in Chinese population, (2) The G6PD variants in Chinese population are different from those in African, European, and Indian populations, (3) A novel G6PD-deficiency mutation, 274C-->T, has been found, and (4) Denaturing high performance liquid chromatography is of great advantage to detecting G6PD-deficient mutations for diagnosis and genetic counseling. Moreover, functional analysis of the human G6PD variants showed the following: (1) The charge property, polarity, pK-radical and side-chain radical of the substituting amino acid have an effect on G6PD activity, (2) The G6PDArg459 and Arg463 play important roles in anchoring NADP+ to the catalytic domain to maintain the enzymatic activity, and (3) The sequence from codon 459 to the carboxyl terminal is essential for the enzymatic function.

Amino Acid Substitution↗
PubMed2003

Towards understanding human mitochondrial leucine aminoacylation identity.

Specific recognition of tRNAs by aminoacyl-tRNA synthetases is governed by sets of aminoacylation identity elements, well defined for numerous prokaryotic systems and eukaryotic cytosolic systems. Only restricted information is available for aminoacylation of human mitochondrial tRNAs, despite their particularities linked to the non-classical structures of the tRNAs and their involvement in a growing number of human neurodegenerative disorders linked to mutations in the corresponding tRNA genes. A major difficulty to be overcome is the preparation of active in vitro transcripts enabling a rational mutagenic analysis, as is currently performed for classical tRNAs. Here, structural and aminoacylation properties of in vitro transcribed tRNA(Leu(UUR)) are presented. Solution probing using a combination of enzymatic and chemical tools revealed only partial folding into an L-shaped structure, with an acceptor branch but with a floppy anticodon branch. Optimization of aminoacylation conditions allowed charging of up to 75% of molecules, showing that, despite its partially relaxed structure, in vitro transcribed tRNA(Leu(UUR)) is able to adapt to the synthetase. In addition, mutational analysis demonstrates that the discriminator base as well as residue A14 are important leucine identity elements. Thus, human mitochondrial leucylation is dependent on rules similar to those that apply in Escherichia coli. The impact of a subset of pathology-related mutations on aminoacylation and on tRNA structure, has been explored. These variants do not show significant structural rearrangements and either do not affect aminoacylation (mutations T3250C, T3271C, C3303T) or lead to marked effects. Interestingly, two variants with a mutation at the same position (A3243G and A3243T) lead to markedly different losses in aminoacylation efficiencies (tenfold and 300-fold, respectively).

Base Sequence↗
PubMed2001

Solution structures of the antifungal heliomicin and a selected variant with both antibacterial and antifungal activities.

In response to an experimental infection, the lepidopteran Heliothis virescens produces an antifungal protein named heliomicin. Heliomicin displays sequence similarities with antifungal plant defensins and antibacterial or antifungal insect defensins. To gain information about the structural elements required for either antifungal or antibacterial activity, heliomicin and selected point-mutated variants were expressed in yeast as fusion proteins. The effects of mutations, defined by comparing the primary structure of heliomicin with the sequences of members of the insect defensin family, were analyzed using antibacterial and antifungal assays. One of the variants shows significant activity against Gram-positive bacteria while remaining efficient against fungi. The three-dimensional structures of this variant and of the wild-type protein were determined by two-dimensional (1)H NMR to establish a correlation between structure and antibacterial or antifungal activity. Wild-type and mutated heliomicins adopt a similar scaffold, including the so-called cysteine-stabilized alphabeta motif. A comparison of their structures with other defensin-type molecules indicates that common hydrophobic characteristics can be assigned to all the antifungal proteins. A comparative analysis of various structural features of heliomicin mutant and of antibacterial defensins enables common properties to be assessed, which will help to design new mutants with increased antibacterial activity.

Amino Acid Sequence↗
PubMed1995

Site-directed mutagenesis of Lys36 in human thioredoxin: the highly conserved residue affects reduction rates and growth stimulation but is not essential for the redox protein's biochemical or biological properties.

Previous studies have demonstrated that a recombinant form of the human redox protein thioredoxin can stimulate the growth rate of Swiss 3T3 murine fibroblasts and that this ability to promote cellular proliferation was dependent upon a redox-active form. A site-directed mutagenesis study of the highly conserved Lys36 adjacent to the two active site cysteines of thioredoxin was performed to determine whether the basic residue was essential for the biochemical and mitogenic properties of human thioredoxin. Two mutants were generated in which the lysine residue was replaced with either glutamic acid (K36E) or leucine (K36L). While K36E and K36L were both redox-active in a thioredoxin-specific assay, the mutants exhibited decreased affinities for thioredoxin reductase relative to wild-type thioredoxin since their respective KM values increased by a factor of 5 and 7. Examination of the secondary structure of the variants by circular dichroism spectroscopy revealed that both mutants had minor variations in the overall structural content when compared to thioredoxin, with K36L being most similar to the wild-type protein. Thermal equilibrium denaturation studies of the variants showed that K36E had a TM of 69.5 degrees C. A TM value for thioredoxin and K36L could not be established because the absence of a plateau above 83 degrees C rendered it difficult to establish an upper base line and, hence, the TM. The two mutants were able to stimulate cellular proliferation, albeit with reduced efficiency when compared with wild-type thioredoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed2005

Solution structure of a natural CPPC active site variant, the reduced form of thioredoxin h1 from poplar.

Assignment of heteronuclear and homonuclear multidimensional NMR spectra permits determination of the first three-dimensional solution structure of a higher-plant thioredoxin h. The collection of 1906 distance restraints, 137 TALOS-derived dihedral restraints, and 66 hydrogen bonds was used in the restrained molecular dynamics protocol to calculate the structure of the reduced form of thioredoxin h1 from poplar with an atomic rmsd of 0.60 +/- 0.12 A. This enzyme exhibits an unusual active site with the sequence WCPPC and original properties in terms of stability and specificity. Compared to other known thioredoxin structures, thioredoxin h1 from poplar adopts the classical "Trx fold". Its atypical active site possesses a conformation similar to that of other common thioredoxins but appears to be more rigid. Moreover, the hydrogen bond network, stabilizing the in-core beta-sheet, is tighter than in Chlamydomonas reinhardtii, explaining the difference in thermostability.

Amino Acid Sequence↗
PubMed2005

Dynamics of the fragment of thrombomodulin containing the fourth and fifth epidermal growth factor-like domains correlate with function.

Thrombomodulin (TM) forms a 1:1 complex with thrombin. Whereas thrombin alone cleaves fibrinogen to make the fibrin clot, the thrombin-TM complex cleaves protein C to initiate the anticoagulant pathway. The fourth and fifth EGF-like domains of TM together form the minimal fragment with anticoagulant cofactor activity. A short linker connects the fourth and fifth EGF-like domains of TM, and Met 388 in the middle of the linker interacts with both domains. Several different structures of TMEGF45 variants are now available, and these show that mutation of Met 388 alters the structure of the fifth domain, as well as the connectivity of the two domains. To probe this phenomenon more thoroughly, NMR backbone dynamics experiments have been carried out on the individual fourth and fifth domains as well as on the wild type, the Met 388 Leu mutant, and the variant in which Met 388 is oxidized. The results presented here show that changes at Met 388 cause significant changes in backbone dynamics in both the fourth and fifth EGF-like domains of TM. Backbone dynamics within the small loop of the fourth domain Tyr 358 correlate with anticoagulant cofactor activity. Backbone dynamics of the thrombin-binding residues Tyr 413 and Ile 414 are inversely correlated with thrombin binding. The preordering of the backbone of Tyr 413 and Ile 414 only occurs in the two-domain fragments, revealing a role for the fourth domain in thrombin binding as well as in anticoagulant cofactor activity.

Amino Acid Substitution↗
PubMed2003

Impact of selection, mutation rate and genetic drift on human genetic variation.

The accumulation of genome-wide information on single nucleotide polymorphisms in humans provides an unprecedented opportunity to detect the evolutionary forces responsible for heterogeneity of the level of genetic variability across loci. Previous studies have shown that history of recombination events has produced long haplotype blocks in the human genome, which contribute to this heterogeneity. Other factors, however, such as natural selection or the heterogeneity of mutation rates across loci, may also lead to heterogeneity of genetic variability. We compared synonymous and non-synonymous variability within human genes with their divergence from murine orthologs. We separately analyzed the non-synonymous variants predicted to damage protein structure or function and the variants predicted to be functionally benign. The predictions were based on comparative sequence analysis and, in some cases, on the analysis of protein structure. A strong correlation between non-synonymous, benign variability and non-synonymous human-mouse divergence suggests that selection played an important role in shaping the pattern of variability in coding regions of human genes. However, the lack of correlation between deleterious variability and evolutionary divergence shows that a substantial proportion of the observed non-synonymous single-nucleotide polymorphisms reduces fitness and never reaches fixation. Evolutionary and medical implications of the impact of selection on human polymorphisms are discussed.

Animals↗
PubMed1977

Hemoglobin Pontoise alpha63 Ala replaced by Asp(E12). A new fast moving variant.

The present report describes structural and functional studies of a new hemoglobin variant, Hb J Pontoise. This abnormal hemoglobin was discovered in a 36 year old Spanish man. The substitution of alpha63 (E12) Ala replaced by Asp is situated at an external site and appears to have no influence on the function of the hemoglobin. Nevertheless, it presents some instability in vitro, as demonstrated by the isopropanol test. This instability could partially explain the low percentage of the abnormal hemoglobin in the hemolysate (12%), since its rate of synthesis was normal.

Adult↗