SEARCH · Search PubMed

Results for “Structure 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.

SourceResearch connectionFrom yearThrough year

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

At least 1,549 records · Page 86Linked to original sources

PubMed1994

Adipose differentiation in cystosarcoma phyllodes. A study of 14 cases.

Adipose differentiation is an uncommon stromal alteration in cystosarcoma phyllodes (CP). We have studied 14 lesions to define the structural variation and prognostic significance of these rare forms of CP. All patients were women between 17 and 71 years of age (mean 40 years; median 42 years). Most were first seen with a mass; three were pregnant. Grossly, the lesions were circumscribed with lobulated cut surfaces. Microscopically, the mesenchymal component showed adipose differentiation that ranged from mature fat to liposarcoma with well-differentiated, myxoid, or pleomorphic components. Six lesions were high-grade malignant CP with immature cellular mesenchyme, abundant mitoses, and areas of pleomorphic liposarcoma. Seven tumors were low-grade malignant CP with few mitoses, relatively low cellularity, and myxoliposarcoma. One tumor with slight periductal condensation and mature adipose tissue was a benign CP, which we named lipophyllodes tumor. Two patients had concurrent breast carcinoma, and two others subsequently had carcinoma. The follow-up was 8-90 months (mean 46 months; median 39 months). There was one recurrence among eight patients treated with simple excision and no recurrences in six treated with mastectomy. One woman died of metastatic breast carcinoma. All others are alive and free of disease. CP with adipose differentiation can be graded histologically on the basis of this component. Despite the high-grade histology in some instances, the patients had an excellent prognosis when the tumors were completely excised.

Adipose Tissue↗

PubMedDate not supplied

Identification of peak stresses in cardiac prostheses. A comparison of two-dimensional versus three-dimensional principal stress analyses.

This study assessed the accuracy of using a two-dimensional principal stress analysis compared to a three-dimensional analysis in estimating peak turbulent stresses in complex three-dimensional flows associated with cardiac prostheses. Three-component, coincident laser Doppler anemometer measurements were obtained in steady flow downstream of three prosthetic valves: a St. Jude bileaflet, Bjork-Shiley monostrut tilting disc, and Starr-Edwards ball and cage. Two-dimensional and three-dimensional principal stress analyses were performed to identify local peak stresses. Valves with locally two-dimensional flows exhibited a 10-15% underestimation of the largest measured normal stresses compared to the three-dimensional principal stresses. In nearly all flows, measured shear stresses underestimated peak principal shear stresses by 10-100%. Differences between the two-dimensional and three-dimensional principal stress analysis were less than 10% in locally two-dimensional flows. In three-dimensional flows, the two-dimensional principal stresses typically underestimated three-dimensional values by nearly 20%. However, the agreement of the two-dimensional principal stress with the three-dimensional principal stresses was dependent upon the two velocity-components used in the two-dimensional analysis, and was observed to vary across the valve flow field because of flow structure variation. The use of a two-dimensional principal stress analysis with two-component velocity data obtained from measurements misaligned with the plane of maximum mean flow shear can underpredict maximum shear stresses by as much as 100%.

Heart Valve Prosthesis↗

PubMed2003

Genetic association between the phospholipase A2 gene and unipolar affective disorder: a multicentre case-control study.

The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder.

Case-Control Studies↗

PubMed2025

How Does Tendon Region, Donor, and the Presence of Disease Affect Protein Composition of the Achilles Tendon?

BACKGROUND: Response to treatment for tendinopathy is variable, which may reflect variability in underlying etiology and capacity for the tendon to respond to treatment. Understanding variability in tendon protein composition may help improve our understanding of the mechanistic underpinnings of painful tendon degeneration and inform treatment targets. QUESTIONS/PURPOSES: (1) What factors (tendon region, individual characteristics, presence of disease) contribute to protein compositional (proteomic) and structural variation in human Achilles tendons? (2) What compositional changes characterize tendinopathy, and what protein interactions might contribute to tendon degeneration? (3) How does diabetes influence tendon composition, and what mechanisms might underlie tendon dysfunction in individuals with diabetes? METHODS: In this exploratory, cross-sectional study, human Achilles tendon specimens were obtained from individuals with (diabetes group, n = 5) or without diabetes (control group, n = 5) undergoing lower extremity amputation and from individuals undergoing tendon debridement surgeries for tendinopathy (tendinopathy group, n = 8). Specimens were collected between 2019 and 2023. Protein abundances were quantified and analyzed using mass spectrometry, hierarchical clustering, and principal component analysis. To evaluate the role of tendon region and donor on tendon protein compositional variability, we assessed proteomic differences between three regions in nontendinopathic tendons from three individuals. To identify the contribution of disease (that is, presence of tendinopathy or diabetes) on protein composition, we compared tendons from the tendinopathy (n = 8 [2 males, 6 females], mean ± SD age 48 ± 11 years), diabetes (n = 5 [3 males, 2 females], age 54 ± 9 years), and control (n = 5 [3 males, 2 females], age 42 ± 12 years) groups. Proteomic differences associated with tendinopathy and diabetes were further examined using functional enrichment and protein-protein interaction network analysis. RESULTS: Variability in tendon protein composition was primarily from presence of disease, followed by donor and then tendon region. Protein composition distinguished tendons with tendinopathy from controls, with 311 proteins differentially expressed (152 overexpressed and 159 underexpressed; fold change ≥ 1.5, p < 0.05) and higher Bonar scores indicating greater degeneration (mean ± SD Bonar score tendinopathy group 8.6 ± 1.2 versus control group 2.1 ± 0.7; p = 0.01). Pathway analysis identified dysregulation in extracellular matrix remodeling (TIMP1, MMP3, MMP10), inflammatory response (TNF-α, EGFR1), and metabolic reprogramming. Tendons from individuals with diabetes exhibited minimal proteomic changes compared with the control group, with 66 differentially expressed proteins (31 overexpressed and 35 underexpressed; fold change ≥ 1.5, p < 0.05) with no histopathologic differences between diabetes and control group tendons (mean ± SD Bonar score diabetes group 3.4 ± 1.0 versus control group 2.1 ± 0.7; p = 0.19). Tendons in the diabetes group showed reductions in Type I collagen, enrichment of pathways associated with fibrosis and metabolic dysfunction, and inflammatory pathways associated with α 6 β 4 integrin. CONCLUSION: Our findings indicate that Achilles tendon composition primarily differs based on disease etiology, with tendinopathy showing extensive extracellular matrix disruption and inflammatory activity, whereas tendons from individuals with diabetes exhibit more subtle compositional changes. This distinction suggests that tendinopathy may require targeted interventions addressing tissue remodeling and inflammation, whereas diabetes may predispose tendons to injury but not directly result in degeneration. Understanding these protein compositional variations can help refine hypotheses about disease progression, treatment response, and potential therapeutic targets. CLINICAL RELEVANCE: While proteomic analysis is not currently a part of routine clinical assessment, these findings provide a framework for identifying protein markers that may aid in early diagnosis or patient stratification to improve treatment alignment. Future studies could determine whether these proteomic changes correlate with treatment response and further inform our understanding of early-stage degeneration from chronic disease. By bridging molecular findings with clinical presentation, this study lays the groundwork for future research on precision medicine approaches for tendon disorders, with the long-term goal of tailoring treatment based on both biological and symptomatic characteristics.

Humans↗

PubMed2004

Methods for determining stability in continuum elastic-rod models of DNA.

Elastic-rod models of DNA have offered an alternative method for studying the macroscopic properties of the molecule. An essential component of the modelling effort is to identify the biologically accessible, or stable, solutions. The underlying variational structure of the elastic-rod model can be exploited to derive methods that identify stable equilibrium configurations. We present two methods for determining the stability of the equilibria of elastic-rod models: the conjugate-point method and the distinguished-diagram method. Additionally, we apply these methods to two intrinsically curved DNA molecules: a DNA filament with an A-tract bend and a DNA minicircle with a catabolite gene activator protein binding site. The stable solutions of these models provide visual insight into the three-dimensional structure of the DNA molecules.

Base Sequence↗

PubMed1980

Symmetrical arrangement of the heterologous regions of rabbit poxvirus and vaccinia virus DNA.

Cleavage sites for the restriction endonucleases EcoRI, KpnI and XhoI were mapped on rabbit poxvirus and vaccinia virus DNA. These physical maps were used to analyse the structural variations between the two DNAs. Two specific heterologous regions, symmetrically arranged at each end of the genomes, have been identified. Region 1, representing the exterior part of the terminal repetition, appears to contain unrelated sequences in each DNA and accounts for the difference in length of the two genomes. Region 2, separated from region 1 by a conserved part of the terminal repetition, is located at the transition from repeated to unique DNA sequences. Its overall length of about 4 megadaltons is well conserved and it contains individual DNA-specific as well as conserved restriction sites. The major central part of the genomes (over 100 megadaltons) contains very few, widely dispersed restriction site variations.

Base Sequence↗

PubMed1981

Antigenic and structural relatedness among non-capsid and capsid polypeptides of polioviruses belonging to different serotypes.

Antibodies were raised by immunization of Macaca fascicularis monkeys with extracts of M. fascicularis kidney cells separately infected with one of the three poliovirus serotypes. Preparations of antibodies were shown to be strictly type-specific in the neutralization test but formed immune complexes adsorbable on Staphylococcus aureus, Cowan I strain cells, with heterotypic as well as homotypic virus-specific polypeptides present in extracts from the virus-infected cells. The presence of intertypic antigenic determinants was demonstrated by this technique on both the non-capsid and capsid poliovirus polypeptides. Structural variations of poliovirus polypeptides were studied by analysing products of their partial proteolysis. Non-capsid polypeptides encoded in the central portion of the virus genome (polypeptides 5b and X) as well as in the 3'-terminal region (NCVP2 and NCVP4) were found to be highly conserved, whereas capsid polypeptides VP1, VP2, and VP3, which are encoded in the 5'-terminal region of the virus RNA, displayed a much greater variability.

Antigens, Viral↗

PubMed1983

Analyses of structural polypeptides of seven different isolates of influenza C virus.

The major structural polypeptides (gp88, NP and M) of seven different influenza C virus strains isolated between 1947 and 1981 in U.S.A. and Japan were compared by SDS-polyacrylamide gel electrophoresis and one-dimensional mapping of the peptide fragments produced after limited proteolysis with various proteases. Of the three polypeptides analysed, the membrane (M) protein appeared to be the most highly conserved since the electrophoretic mobility as well as the mapping pattern of this protein was found to be identical among all seven strains. The structure of nucleoprotein (NP) was also found to be highly conserved. The proteins of five isolates from 1964 to 1981 showed migration rates and mapping patterns indistinguishable from each other though they were slightly different in mapping patterns from the earlier isolates, C/Taylor/1233/47 and C/JJ/50. The similarities between influenza C strains were also evident with the surface glycoprotein, gp88. The gp88 proteins of the five strains isolated in 1947, 1950, 1971 and 1981 were virtually identical in migration rates as well as in mapping patterns, while the two isolates of 1964 and 1974 showed minor differences. These results strongly suggest that the surface glycoprotein of influenza C virus is structurally much more stable than the haemagglutinin and neuraminidase glycoproteins of influenza A and B viruses. Further, the findings that differences from the original influenza C strain, Taylor/1233/47 were detectable in the strains isolated in 1964 and 1974 but not in the strains isolated in 1971 and 1981 suggest that unlike the antigenic drift of types A and B influenza viruses, the structural variation of gp88 may not be a sequential event.

Electrophoresis, Polyacrylamide Gel↗

PubMed1993

Conserved and variable regions in protein Arp, the IgA receptor of Streptococcus pyogenes.

The streptococcal M protein family, a number of cell surface molecules that interact with the human immune system, can be divided into two major classes, A and C, characterized by different types of repeats in the central part of the molecule. Class A and class C molecules are known to have a variable N-terminal region and a more conserved C-terminal region, but little is known about the mechanisms that give rise to this structural variation. In this report, we show that two variants of protein Arp, an IgA receptor in class C of the M protein family, have virtually identical signal sequences and C-terminal halves, but unrelated N-terminal sequences. Comparison of the sequences of the two genes and their flanking regions also demonstrates the presence of well-defined variable and conserved regions. Our results strongly suggest that the N-terminal sequence variation between the two variants of protein Arp was generated through an intergenic recombination event, rather than through intragenic recombination or accumulation of mutations.

Amino Acid Sequence↗

PubMed2025

A personalized multi-platform assessment of somatic mosaicism in the human frontal cortex.

Somatic mutations in individual cells create genomic mosaicism, influencing genetic disorders and cancers. While clonal mutations in cancers are well-studied, rarer somatic variants in normal tissues remain poorly characterized. This study systematically evaluates detection methods using a personalized donor-specific assembly (DSA) from a neurotypical individual's dorsolateral prefrontal cortex assessed with Oxford Nanopore, NovaSeq, linked-read sequencing, Cas9-targeted long-read sequencing (TEnCATS), and single-neuron MALBAC amplification. The haplotype-resolved DSA improved cross-platform analysis, dramatically increasing phasing rates. Germline SNVs, structural variations (SVs), and transposable elements (TEs) were recalled with 99.4%-99.7% accuracy in bulk tissue, and phased haplotype analysis reduced false positives by 15.4%-75.1% for putative somatic candidates. Long-read single-neuron sequencing detected nine somatic SV candidates, demonstrating enhanced sensitivity for rare variants, while TEnCATS identified eight low-frequency somatic TE candidates. These findings highlight advanced methodologies for precise somatic variant detection, critical for understanding mosaicism's role in health and disease.

Multi-platform Sequencing↗

PubMed2025

Diploid genome assembly of human fibroblast cell lines enables clone specific variant calling, improved read mapping and accurate phasing.

Human cell lines are fundamental tools in biomedical research and are widely used in disease modeling, drug development, and many other domains. Here, we present chromosome-level, phased diploid genome assemblies of two popular human cell lines: the BJ foreskin fibroblast line and the IMR-90 fetal lung fibroblast line. Our high-quality assemblies, generated using long-read and Hi-C sequencing data, reveal substantial structural variation, including more than 50,000 insertions, deletions, duplications, and inversions compared to the recent T2T-CHM13v2.0 reference. Our assemblies provide detailed maps of genetic variation, enabling more accurate variant calling and the ability to phase reads when using newly generated or historical sequencing data on these cell lines or their derivatives. All assemblies and associated data have been made available as a resource for the research community. We envision that diploid genome assembly will become a cornerstone approach for personalized medicine in the near future.

Journal Article↗

PubMed2025

An allelic resolution gene atlas for tetraploid potato provides insights into tuberization and stress resilience.

Tubers are modified underground stems that enable asexual, clonal reproduction and serve as a mechanism for overwintering and avoidance of herbivory. Tubers are wide-spread across angiosperms with some species such as Solanum tuberosum L. (potato) serving as a vital crop for human consumption. Genes responsible for tuber initiation and disease resistance have been characterized in potato including StSP6A, a homolog of Flowering Time, that functions as tuberigen, the equivalent of florigen. To elucidate additional molecular and genetic mechanisms underlying potato biology including tuber initiation, tuber development, and stress responses, we generated a developmental and abiotic/biotic-stress gene expression atlas from 34 tissues and treatments of Atlantic, a tetraploid cultivar. Using the haplotype-phased tetraploid Atlantic genome assembly and expression abundances of 129,218 genes, we constructed gene coexpression modules that represent networks associated with distinct developmental stages as well as stress responses. Functional annotations were given to modules and used to identify genes involved in tuberization and stress resilience. Structural variation from a pan-genomic analysis across four cultivated potato genome assemblies as well as domestication and wild introgression data allowed for deeper insights into the modules to identify key genes involved in tuberization and stress responses. This study underscores the importance of transcriptional regulation in tuberization and provides a comprehensive framework for future research on potato development and improvement.

Journal Article↗

PubMed2025

MarkerMatch: A Proximity-Based Probe-Matching Algorithm for Joint Analysis of Copy-Number Variants from Different Genotyping Arrays.

MOTIVATION: Copy-number variants (CNVs) are a form of genetic structural variation with increasing importance in complex human disorders. Both DNA sequencing and microarray data can be used to call CNVs, which can be used in association tests, such as association between CNV number and disease status. Unlike genotypes, CNV detection in microarrays requires the use of observed intensity signals at each probe, which limits the imputability for analyses that span multiple array types. Thus far, a consensus set of probes (the intersection encompassing the probes that occur in common on all arrays) has been used to circumvent the problem of differing array-specific sensitivities. This has, however, led to excessive reduction in overall sensitivity of CNV calls as arrays can have an undesirably low overlap of probe sets. To overcome this limitation, we developed MarkerMatch, a proximity-based algorithm that matches probes across different genotyping microarrays to maximize the number of probes considered in the CNV calling algorithm, thereby increasing the resolution and sensitivity while preserving precision. RESULTS: By analyzing CNV calls from 4,906 individuals genotyped across three different arrays (Global Screening Array, Omni2.5 array, and Omni Express Exome array), we show that the MarkerMatch approach improves sensitivity by increasing the density of probes available for CNV calling while maintaining precision or improving it relative to the current practice (e.g., use of consensus probes only). We further demonstrate that MarkerMatch exceeds the output from current practice in terms of F1 score, Fowlkes-Mallows index, and Jaccard index. We also optimize MarkerMatch parameters, D MAX and Method, and find an optimal D MAX setting at 10kb, with no clear optimal candidate based on Method, indicating that parameters for this metric should be determined on a use case basis.

Journal Article↗

PubMed2025

Defining and cataloging variants in pangenome graphs.

Structural variation causes some human haplotypes to align poorly with the linear reference genome, leading to 'reference bias'. A pangenome reference graph could ameliorate this bias by relating a sample to multiple reference assemblies. However, this approach requires a new definition of a 'genetic variant.' We introduce a definition of pangenome variants and a method, pantree, to identify them. Our approach involves a pangenome reference tree which includes all nodes (sequences) of the pangenome graph, but only a subset of its edges; non-reference edges are variant edges. Our variants are biallelic and have well-defined positions. Analyzing the Minigraph-Cactus draft human pangenome reference graph, we identified 29.6 million genetic variants. Most variants (99.2%) are small, and most small variants (73.9%) are SNPs. 3.5 million variants (11.7%) have a reference allele which is not on GRCh38; these variants are difficult to detect without a pangenome reference, or with existing pangenome-based approaches. They tend to be embedded within tangled, multiallelic regions. We analyze two medically relevant regions, around the HLA-A and RHD genes, identifying thousands of small variants embedded within several large insertions, deletions, and inversions. We release an open-source software tool together with a VCF variant catalogue.

Journal Article↗

PubMed2025

PARTAGE: Parallel analysis of replication timing and gene expression.

The human genome is partitioned into functional compartments that replicate at specific times during the S-phase. This temporal program, referred to as replication timing (RT), is co-regulated with the 3D genome organization, is cell type-specific, and changes during development in coordination with gene expression. Moreover, RT alterations are linked to abnormal gene expression, genome instability, and structural variation in multiple diseases, including cancer. However, mechanistic links between RT, large-scale 3D genome architecture, and transcriptional regulation remain poorly understood. A major limitation is that current approaches require the separate profiling of RT and transcriptomes from independent batches of samples, obscuring the complex co-regulation between the epigenome and transcriptome. Here, we developed PARTAGE, a multiomics approach that enables joint profiling of copy number variation (CNV), RT, and gene expression from the same sample, providing a more accurate integrative view of the complex relationships between RT and gene regulation.

Journal Article↗

PubMed2025

Panorama of Chromosomal Instability in Lung Cancer.

Lung cancer is a highly heterogeneous disease primarily driven by tobacco smoking. About 20% of lung cancers occur among patients who have never smoked (LCINS) with differences in patient ancestry, sex, tumor histology, and clinical features. Our understanding of chromosomal instability in lung cancer, especially LCINS, is still limited. Here, we perform a comprehensive study of 182,429 somatic structural variations (SVs) detected in 1,209 whole-genome sequenced lung cancers, of which 864 LCINS. SVs are more abundant in tumors from patients who have smoked (LCSS); however, they are more complex and play more important roles in tumorigenesis in LCINS. EGFR mutations and KRAS mutations profoundly and independently shape the SV landscape. EGFR-mutant tumors have higher SV burden and more cancer-driving SVs. In contrast, KRAS mutations are associated with lower SV burden and less driver SVs. We decompose 16 SV signatures for both complex and simple SVs that likely represent divergent molecular mechanisms. The SV breakpoints have distinct distributions across the genome depending on the signatures due to mutagenic mechanisms and positive selection. Many established cancer-driving genes are recurrently rearranged by multiple SV signatures suggesting functional convergence of these genome instability mechanisms.

Journal Article↗

PubMed2006

A preliminary comparative analysis of primate segmental duplications shows elevated substitution rates and a great-ape expansion of intrachromosomal duplications.

Compared with other sequenced animal genomes, human segmental duplications appear larger, more interspersed, and disproportionately represented as high-sequence identity alignments. Global sequence divergence estimates of human duplications have suggested an expansion relatively recently during hominoid evolution. Based on primate comparative sequence analysis of 37 unique duplication-transition regions, we establish a molecular clock for their divergence that shows a significant increase in their effective substitution rate when compared with unique genomic sequence. Fluorescent in situ hybridization (FISH) analyses from 1053 random nonhuman primate BACs indicate that great-ape species have been enriched for interspersed segmental duplications compared with representative Old World and New World monkeys. These findings support computational analyses that show a 12-fold excess of recent (>98%) intrachromosomal duplications when compared with duplications between nonhomologous chromosomes. These architectural shifts in genomic structure and elevated substitution rates have important implications for the emergence of new genes, gene-expression differences, and structural variation among humans and great apes.

Animals↗

PubMed1971

Specificity of deoxyribonucleic Acid intercalating compounds in the control of phenylalanine ammonia lyase and pisatin levels.

Compounds with planar triple ring systems such as acridine orange, 9-amino acridine, 9-amino-1,2,3,4-tetrahydroacridine (tacrine), 6,9-diamino-2-ethoxyacridine lactate monohydrate (DE-acridine), 6-chloro-9-(3'-diethylamino-2'-hydroxypropylamino) -2-methoxyacridine.2 HCl (CDM-acridine), quinacrine, 6-chloro-9-(4'-diethylamino-1'-methylbutylamino) -2-methoxy-1,10-diazaanthracene (CDM 1,10-diazaanthracene), thionine, azure A, methylene blue, and pyronine Y when applied to excised pea pods were potent inducers of phenylalanine ammonia lyase or of pisatin, or of both. Compounds with an array of structural variation around the planar three-ring system were tested for their ability to induce these responses in pea tissue. In general, dimethylamino, diethylamino, or amino substitutions at position 2 and 6 or an amino (with or without an aliphatic side chain) substitution at position 9 of the three-ring system augmented induction potential. Methyl green, methylene blue, 2,7-diaminofluorene, nile blue, neutral red, pyrogallol red, ethidium bromide, nogalamycin, quinine, chloroquine, spermine, 8-azaguanine, gliotoxin, chromomycin A(3), actinomycin D, and mitomycin C were also potent inducers. The inhibition of phenylalanine ammonia lyase induction by the application of actinomycin D (300 micrograms per milliliter) or 6-methylpurine (1 milligram per milliliter) within 1 hour after inducer application indicated that newly synthesized RNA is necessary for induction. Phenylalanine ammonia lyase induction was also inhibited by cycloheximide (150 micrograms per milliliter).

Journal Article↗