Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “structural variation”

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 577 records · Page 32Linked to original sources
PubMedDate not supplied

Acetylcholinesterase staining in human auditory and language cortices: regional variation of structural features.

Cholinergic innervation of the cerebral neocortex arises from the basal forebrain and projects to all cortical regions. Acetylcholinesterase (AChE), the enzyme responsible for deactivating acetylcholine, is found within both cholinergic axons arising from the basal forebrain and a subgroup of pyramidal cells in layers III and V of the cerebral cortex. This pattern of staining varies with cortical location and may contribute uniquely to cortical microcircuitry within functionally distinct regions. To explore this issue further, we examined the pattern of AChE staining within auditory, auditory association, and putative language regions of whole, postmortem human brains. The density and distribution of acetylcholine-containing axons and pyramidal cells vary systematically as a function of auditory processing level. Within primary auditory regions AChE-containing axons are dense and pyramidal cells are largely absent. Adjacent cortical regions show a decrease in the density of AChE-containing axons and an increase in AChE-containing pyramidal cells. The posterior auditory and language regions contain a relatively high density of AChE-containing pyramidal cells and AChE-containing axons. Although right and left posterior temporal regions are functionally asymmetrical, there is no apparent asymmetry in the general pattern of AChE staining between homologous regions of the two hemispheres. Thus, the pattern of AChE staining covaries with processing level in the hierarchy of auditory cortical regions, but does not vary between the functionally distinct right and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cells was present within a number of cortical regions. Large AChE-rich pyramidal cells of layer III were consistently greater in size in the left hemisphere as compared to the right. Asymmetry in layer III pyramidal cell size was not restricted to language-associated regions, and could potentially have a variety of etiologies including structural, connectional, and activational differences between the left and right hemisphere.

Acetylcholinesterase↗
PubMed2005

Structure and variation of three canine genes involved in serotonin binding and transport: the serotonin receptor 1A gene (htr1A), serotonin receptor 2A gene (htr2A), and serotonin transporter gene (slc6A4).

Aggressive behavior is the most frequently encountered behavioral problem in dogs. Abnormalities in brain serotonin metabolism have been described in aggressive dogs. We studied canine serotonergic genes to investigate genetic factors underlying canine aggression. Here, we describe the characterization of three genes of the canine serotonergic system: the serotonin receptor 1A and 2A gene (htr1A and htr2A) and the serotonin transporter gene (slc6A4). We isolated canine bacterial artificial chromosome clones containing these genes and designed oligonucleotides for genomic sequencing of coding regions and intron-exon boundaries. Golden retrievers were analyzed for DNA sequence variations. We found two nonsynonymous single nucleotide polymorphisms (SNPs) in the coding sequence of htr1A; one SNP close to a splice site in htr2A; and two SNPs in slc6A4, one in the coding sequence and one close to a splice site. In addition, we identified a polymorphic microsatellite marker for each gene. Htr1A is a strong candidate for involvement in the domestication of the dog. We genotyped the htr1A SNPs in 41 dogs of seven breeds with diverse behavioral characteristics. At least three SNP haplotypes were found. Our results do not support involvement of the gene in domestication.

Amino Acid Sequence↗
PubMed2006

Highly structured nucleotide variation within and among Arabidopsis lyrata populations at the FAH1 and DFR gene regions.

Nucleotide variation at the FAH1 and DFR gene regions was surveyed in four populations of Arabidopsis lyrata (two European A. l. petraea and two North American A. l. lyrata populations). In contrast to previous results, levels of variation were not consistently lower in A. l. lyrata than in A. l. petraea, and similar degrees of genetic differentiation were detected between and within subspecies. These observations and the significant genetic differentiation detected among populations suggest population substructure and no real subdivision between subspecies. For each gene studied, genotypic data were obtained, which allowed comparing nucleotide diversity within individuals (between sequences from the same individual) and within populations (between sequences from the same population). The generally lower level of variation within than among individuals detected in each population yielded a significant deviation from panmixia within populations. In three of the four populations studied, two highly divergent alleles were detected within populations at the highly variable DFR locus. This pattern and the significant excess of derived variants detected in most populations suggest that most variation segregating within populations results from rare migration events between relatively small and isolated populations exhibiting reduced panmixia.

Alcohol Oxidoreductases↗
PubMed1977

Monstrous Tetrahymena with intraclonal variation in structure produced by hereditary modification of normal cells.

Monstrous Tetrahymena pyriformis strain GL may be isolated after exposure of normal cells to numerous heat shocks, to flattening on agar or gelatin plates, or to viscous solutions of methyl cellouse. It is shown that in some cases the abnormalities are inherited and that this results in clones where the cells are different from each other and have various abnormalities with respect to cortical pattern, swimming and feeding behavior, and generation time. Furthermore, it is shown that these cells are produced rather than selected by the experimental treatments. Evidence is presented that growth without division is important for production of the abnormal organisms. The basis of the inheritance of the abnormalities is discussed.

Animals↗
PubMed1996

Fimbrial adhesins: similarities and variations in structure and biogenesis.

Fimbriae are wiry (2 to 4 nm diam.) or rod-shaped (6 to 8 nm diam.), fibre-like structures on the surfaces of bacteria which mediate attachment to host cells. Much has been learned in recent years about the biogenesis, structure and regulation of expression of these adhesive organelles in Gram-negative bacteria. Analyses of the genetic determinants encoding the biogenesis of fimbriae has revealed that the adhesive interaction of fimbriae can be mediated by major subunits (CFA/I and CS1 fimbriae) or minor subunits (P, S, and type 1 fimbriae), with the adhesin being located either at the tip of the fimbria or along the length of the fimbrial shaft. Minor subunits can also act as adapters, anchors, initiators or elongators. Post-translational glycosylation of the type 4 pilins of Neisseria gonorrhoeae, Neisseria meningitidis and Pseudomonas aeruginosa has been demonstrated. The structures of the PapD chaperone of Escherichia coli and of N. gonorrhoeae type 4 fimbrin have been resolved at 2.0-2.6 A. Rod-shaped fimbriae should not be thought of as being rigid inflexible structures but rather as dynamic structures which can undergo transition from a helicoidal to a fibrillar conformation to provide a degree of elasticity and plasticity to the fimbriae so that they can resist shear forces, rather like a bungee cord. At least four mechanisms have been identified in the assembly of fimbriae from fimbrin subunits, namely the chaperone-usher pathway (e.g., P-fimbriae of uropathogenic E. coli), the general secretion assembly pathway (e.g., type 4 fimbriae or N-methylphenylalanine fimbriae of P. aeruginosa, the extracellular nucleation-precipitation pathway (e.g., curli of E. coli) and the CFA/I, CS1 and CS2 fimbrial pathway.

Adhesins, Bacterial↗
PubMed2004

Temporal and spatial variations in structural protein expression during the progression from stunned to hibernating myocardium.

BACKGROUND: Dysfunctional and normally perfused remote regions show equal myolysis and glycogen accumulation in pig hibernating myocardium. We tested the hypothesis that these arose secondary to elevations in preload rather than ischemia. METHODS AND RESULTS: Expression of structural protein (desmin, desmoplakin, titin, cardiotin, alpha-smooth muscle actin, lamin-A/C, and lamin-B2) in viable dysfunctional myocardium was analyzed by immunohistochemistry. We performed blinded analysis of paired dysfunctional left anterior descending coronary artery and normal remote subendocardial samples from stunned (24 hours; n=6), and hibernating (2 weeks; n=6) myocardium versus sham controls pigs (n=7). Within 24 hours, cardiac myocytes globally reexpressed alpha-smooth muscle actin. In stunned myocardium, cardiotin was globally reduced, whereas reductions in desmin were restricted to the dysfunctional region. Alterations progressed with the transition to hibernating myocardium, in which desmin, cardiotin, and titin were globally reduced. A qualitatively similar reorganization of cytoskeletal proteins occurred 3 hours after transient elevation of left ventricular end-diastolic pressure to 33+/-3 mm Hg. CONCLUSIONS: Qualitative cardiomyocyte remodeling similar to that in humans with chronic hibernation occurs rapidly after a critical coronary stenosis is applied, as well as after transient elevations in left ventricular end-diastolic pressure in the absence of ischemia. Thus, reorganization of cytoskeletal proteins in patients with viable dysfunctional myocardium appears to reflect chronic and/or cyclical elevations in preload associated with episodes of spontaneous regional ischemia.

Actinin↗
PubMed2005

Variation in structural location and amino acid conservation of functional sites in protein domain families.

BACKGROUND: The functional sites of a protein present important information for determining its cellular function and are fundamental in drug design. Accordingly, accurate methods for the prediction of functional sites are of immense value. Most available methods are based on a set of homologous sequences and structural or evolutionary information, and assume that functional sites are more conserved than the average. In the analysis presented here, we have investigated the conservation of location and type of amino acids at functional sites, and compared the behaviour of functional sites between different protein domains. RESULTS: Functional sites were extracted from experimentally determined structural complexes from the Protein Data Bank harbouring a conserved protein domain from the SMART database. In general, functional (i.e. interacting) sites whose location is more highly conserved are also more conserved in their type of amino acid. However, even highly conserved functional sites can present a wide spectrum of amino acids. The degree of conservation strongly depends on the function of the protein domain and ranges from highly conserved in location and amino acid to very variable. Differentiation by binding partner shows that ion binding sites tend to be more conserved than functional sites binding peptides or nucleotides. CONCLUSION: The results gained by this analysis will help improve the accuracy of functional site prediction and facilitate the characterization of unknown protein sequences.

Amino Acid Sequence↗
PubMed2026

Computational strategies for copy number variation detection, disease association, and beyond.

Copy number variations (CNVs) are key structural variations that contribute to human genetic diversity, evolution, and disease susceptibility. Advances in sequencing technologies and computational methods have improved CNV detection, yet association studies remain challenged by methodological limitations and a lack of standardisation. This review provides an overview of computational strategies for germline CNV detection and disease association. We highlight the value of CNV analysis for uncovering genetic contributions to complex traits and disease risk and outline an analysis workflow including key benchmarking methods. We also discuss current challenges and future directions for advancing CNV detection and association analysis.

Humans↗
PubMed2005

Variations in structural protein expression and endothelial cell proliferation in relation to clinical manifestations of cerebral cavernous malformations.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are associated with hemorrhagic proliferation of endothelial-lined vascular caverns, resulting in hemorrhagic stroke, epilepsy, and other neurological manifestations. We hypothesize that structural protein expression and endothelial cell proliferation markers within CCM lesions are different in the setting of various clinical manifestations. METHODS: The percentage of immunohistochemically stained caverns positive for collagen IV, fibronectin, laminin, alpha-smooth muscle actin, myosin, and smoothelin and the percentage of dividing endothelial cells within caverns were determined in 36 excised CCM surgical specimens. These were compared in CCMs with different multiplicity, location, and size in patients of different age, sex, seizure status, and hemorrhage status. RESULTS: Comparisons of seven lesion features and clinical manifestations with the fraction of caverns containing the structural proteins studied and endothelial cell proliferation demonstrated no significant differences. A possible exception was the difference (P < 0.05) in the fraction (mean +/- standard deviation) of positively stained caverns for collagen IV between adult (0.63 +/- 0.39) and pediatric patients (0.87 +/- 0.21) as well as fewer caverns with laminin expression in older patients. These trends did not sustain significance with Bonferroni's correction for multiple comparisons. CONCLUSION: The fraction of caverns containing the particular structural proteins studied and endothelial cell proliferation within caverns are not correlated with particular lesion features and clinical manifestations that were investigated in CCMs. The possible fewer fractions of caverns containing collagen IV and laminin in adult lesions compared with pediatric lesions may have implications for lesion regression and quiescence with age.

Actins↗
PubMed1990

The effect of variation in structure on the Young's modulus of cancellous bone: a comparison of human and non-human material.

The Young's modulus of cubes of human cancellous bone was measured in three orthogonal directions. Apparent density and mineral volume fraction were also measured, as were two architectural variables, fabric and connectivity, which were determined using image analysis techniques. Multiple regression was used to relate the Young's modulus to the four explanatory variables. The results from this study are compared with those obtained from a previous investigation using non-human cancellous bone. The relationships revealed by the two studies are very similar. It was possible to explain approximately 93 per cent of the variance in Young's modulus using the four variables in this present study. Apparent density is the major explanatory variable in both studies and shows a strong correlation with connectivity. In common with the non-human study the measure of fabric is a worthwhile explanatory variable; however, connectivity and mineral volume fraction are relatively unimportant. The four explanatory variables contribute to a successful model for the prediction of Young's modulus. Any other candidate variables are likely to be unimportant or be highly correlated with those already investigated.

Adult↗