SEARCH · Search PubMed

Results for “Deep phenotyping”

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 577 records · Page 32Linked to original sources

PubMed2024

Whole-genome sequencing in 333,100 individuals reveals rare non-coding single variant and aggregate associations with height.

The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare ( < 0.1% minor-allele-frequency) single-variant and aggregate testing of non-coding variants in regulatory regions based on proximal-regulatory, intergenic-regulatory and deep-intronic annotation. We observed 29 independent variants associated with height at P < after conditioning on previously reported variants, with effect sizes ranging from -7cm to +4.7 cm. We also identified and replicated non-coding aggregate-based associations proximal to HMGA1 containing variants associated with a 5 cm taller height and of highly-conserved variants in MIR497HG on chromosome 17. We have developed an approach for identifying non-coding rare variants in regulatory regions with large effects from whole-genome sequencing data associated with complex traits.

Humans↗

PubMed1997

Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated-dedifferentiated (WD-DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD-DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD-DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD-DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas.

Adolescent↗

PubMed2003

Identification, cloning and characterization of rfaE of Actinobacillus pleuropneumoniae serotype 1, a gene involved in lipopolysaccharide inner-core biosynthesis.

Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and its lipopolysaccharides (LPS) have been identified as important adhesins involved in adherence to host cells. To better understand the role of LPS core in the virulence of this organism, the aim of the present study was to identify and clone genes involved in LPS core biosynthesis by complementation with Salmonella enterica serovar Typhimurium mutants (rfaC, rfaD, rfaE and rfaF). Complementation with an A. pleuropneumoniae 4074 genomic library was successful with Salmonella mutant SL1102. This Salmonella deep-rough LPS mutant is defective for the rfaE gene, which is an ADP-heptose synthase. Novobiocin was used to select transformants that had the smooth-LPS type, since Salmonella strains with wild-type smooth-LPS are less permeable, therefore more resistant to hydrophobic antibiotics like novobiocin. We obtained a clone that was able to restore the wild-type smooth-LPS Salmonella phenotype after complementation. The wild-type phenotype was confirmed using phage (Felix-O, P22c.2 and Ffm) susceptibility and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). One of the open reading frames contained in the 3.3-kb insert in the plasmid encoded a 475-amino-acid protein with 71% identity and 85% similarity to the RfaE protein of S. enterica. We then attempted to generate an A. pleuropneumoniae rfaE mutant by gene replacement. The rfaE gene seems essential in A. pleuropneumoniae viability as we were unable to isolate a heptose-less knockout mutant.

Actinobacillus pleuropneumoniae↗

PubMed2001

Geobacter hydrogenophilus, Geobacter chapellei and Geobacter grbiciae, three new, strictly anaerobic, dissimilatory Fe(III)-reducers.

Recent studies on the diversity and ubiquity of Fe(III)-reducing organisms in different environments led to the isolation and identification of four new dissimilatory Fe(III)-reducers (strains H-2T, 172T, TACP-2T and TACP-5). All four isolates are non-motile, Gram-negative, freshwater, mesophilic, strict anaerobes with morphology identical to that of Geobacter metallireducens strain GS-15T. Analysis of the 16S rRNA sequences indicated that the new isolates belong to the genus Geobacter, in the delta-Proteobacteria. Significant differences in phenotypic characteristics, DNA-DNA homology and G+C content indicated that the four isolates represent three new species of the genus. The names Geobacter hydrogenophilus sp. nov. (strain H-2T), Geobacter chapellei sp. nov. (strain 172T) and Geobacter grbiciae sp. nov. (strains TACP-2T and TACP-5) are proposed. Geobacter hydrogenophilus and Geobacter chapellei were isolated from a petroleum-contaminated aquifer and a pristine, deep, subsurface aquifer, respectively. Geobacter grbiciae was isolated from aquatic sediments. All of the isolates can obtain energy for growth by coupling the oxidation of acetate to the reduction of Fe(III). The four isolates also coupled Fe(III) reduction to the oxidation of other simple, volatile fatty acids. In addition, Geobacter hydrogenophilus and Geobacter grbiciae were able to oxidize aromatic compounds such as benzoate, whilst Geobacter grbiciae was also able to use the monoaromatic hydrocarbon toluene.

Base Composition↗

PubMed1987

Increased Lysine and Seed Storage Protein in Rice Plants Recovered from Calli Selected with Inhibitory Levels of Lysine plus Threonine and S-(2-Aminoethyl)cysteine.

Experiments were designed to test whether variation in percent lysine in seed proteins could be recovered in plants regenerated from callus subjected to inhibitory levels of lysine plus threonine. Anther-derived callus was subjected to 1 millimolar lysine plus threonine for three successive passages and then once to the same concentration of S-(2-aminoethyl)cysteine. Plants were regenerated from the resistant callus. Plants recovered directly from tissue culture were normal in color, size and were 50% or less fertile. Second and third generation plants produced a wide range of variants including albinos, deep green plants both short and tall, and totally fertile as well as partially fertile plants. All regenerated plants produced chalky or opaque seed. One unique second generation line had 14% more lysine in seed storage proteins than the controls. This characteristic was transmitted to the next generation. The high lysine plants had reduced seed size with significantly higher levels of seed storage protein than the controls. The phenotypes recovered provide experimental materials for basic studies in protein synthesis and lysine metabolism and may become a source of material for rice breeding.

Journal Article↗

PubMed1996

Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes.

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (B7) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotypes. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes.

Canada↗

PubMed2006

The challenges of Proteus syndrome: diagnosis and management.

Proteus syndrome (PS) is a disorder of patchy or mosaic postnatal overgrowth of unknown etiology. The onset of overgrowth typically occurs in infancy and can involve any tissue of the body. Commonly involved tissues include connective tissue and bone, skin, central nervous system, the eye, but it apparently can affect any tissue. Diagnosing of PS is difficult and the diagnostic criteria are controversial. Our group advocates stringent diagnostic criteria to facilitate research and appropriate clinical care. The benefit of strict criteria is that they define a clinical group that is reasonably homogenous with respect to manifestations and prognosis. The overgrowth of PS is progressive and can be difficult to manage. The progressive overgrowth most commonly causes severe orthopaedic complications, but it can cause many other complications. One of the most common complications in patients with PS is deep venous thrombosis and pulmonary embolism, which can cause premature death. Effective management requires knowledge of the wide array of manifestations and complications of the disorder and a team approach that includes the geneticist, surgeons, and other specialists.

Female↗

PubMed2005

Pseudomonas pachastrellae sp. nov., isolated from a marine sponge.

Two Gram-negative, non-fermentative, non-denitrifying, non-pigmented, rod-shaped bacteria that were motile by means of polar flagella, designated strains KMM 330(T) and KMM 331, were isolated from a deep-sea sponge specimen and subjected to a polyphasic taxonomic study. The new isolates exhibited 16S rRNA gene sequence similarity of 99.9 %, and their mean level of DNA-DNA relatedness was 82 %. Phylogenetic analysis based on their 16S rRNA gene sequences placed the strains within the genus Pseudomonas as an independent deep clade. Strain KMM 330(T) shared highest sequence similarity (96.3 %) with each of Pseudomonas fulva NRIC 0180(T), Pseudomonas parafulva AJ 2129(T) and Pseudomonas luteola IAM 13000(T); sequence similarity to other recognized species of the genus Pseudomonas was below 95.7 %. The marine sponge isolates KMM 330(T) and KMM 331 could be distinguished from the other recognized Pseudomonas species based on a unique combination of their phenotypic characteristics, including growth in 8 or 10 % NaCl, the absence of pigments, the inability to denitrify and lack of carbohydrate utilization. On the basis of phylogenetic analysis, physiological and biochemical characterization, strains KMM 330(T) and KMM 331 should be classified as a novel species of the genus Pseudomonas, for which the name Pseudomonas pachastrellae sp. nov. is proposed. The type strain is KMM 330(T) (=JCM 12285(T)=NRIC 0583(T)=CCUG 46540(T)).

Animals↗

PubMed2003

Does bone marrow contain renal precursor cells?

In the past few years stem cells normally present within the bone marrow have been shown to have considerable plasticity in the repertoire of the cells that they produce. They are capable of producing specific lineages of cells not only of the blood, but also contribute usefully to lineages of other organs. In the kidney, studies in humans and rodents provide evidence for the presence of bone marrow-derived 're-programmed' cells, but it remains possible that the cells that arrive and re-differentiate are no longer stem cells (quiescent cells, not actively proliferating). Nevertheless, the fact that appropriately differentiated cells are delivered deep within the kidney simply by injection of bone marrow cells should make us think differently about the way these organs regenerate and repair. Migratory pathways for multipotential stem cells could be exploited to effect repair using an individual's own stem cells, perhaps after gene therapy. It is clear also that a transplanted organ would in time become affected by the genetic susceptibilities of the recipient, because of phenotypes that are expressed when trafficking cells engraft and differentiate.

Animals↗

PubMed1994

Immuno-EM localization of the beta 1 integrin subunit in wet-cleaved fibronectin-adherent fibroblasts.

Using immuno-EM, we have studied the distribution of the beta 1 integrin subunit in chicken embryo fibroblasts allowed to adhere and spread for 3 hours on a fibronectin-coated surface in serum-free medium. The cells were wet-cleaved, which removed most of the cell body, yielding ventral plasma membranes with little, and sometimes virtually no, associated cytoskeleton. The beta 1 integrin subunit was detected with antibodies against the cytoplasmic domain. In immune fluorescence, it colocalized with adhesion plaques, in a punctate staining pattern, and often seemed to be at the periphery of the plaque. By immuno-EM, beta 1 was in fact found in discrete clusters, not throughout the plaque. In deep-cleaved cells from which virtually all cytoskeleton was removed, clusters could often be seen to be located on fibronectin fibrils. Furthermore, beta 1 was present in clusters at the cell margins, and isolated or in small groups at the very edge of the cell. When fibronectin synthesis, and consequently fibril formation, was inhibited by cycloheximide, large adhesion plaque-like structures were formed at the cell margin. This phenotype was reversed by addition of soluble fibronectin, which was incorporated into fibrils. As in normal plaques, talin and vinculin were present, the plasma membrane was very close (10-20 nm) to the substratum and the fibronectin layer underneath was removed. These plaques did contain beta 1 integrins but they were not in clusters. These observations indicate that the talin-vinculin network of an adhesion plaque is normally anchored to the substratum at discrete beta 1 integrin clusters that may be located on fibronectin fibrils, and that elsewhere the plaque is not necessarily attached to the substratum by interaction of integrins with matrix proteins. In the absence of fibronectin fibrils, adhesion plaque-like structures can be formed, but these are aberrant in size, location and fine structure.

Animals↗

PubMed2004

Cluster headache: focus on emerging therapies.

Cluster headache is a strictly unilateral headache that occurs in association with cranial autonomic features. It is an excruciating syndrome and is probably one of the most painful conditions known to mankind with female patients describing each attack as being worse than childbirth. In most patients, it has a striking circannual and circadian periodicity. This disorder has a highly stereotyped clinical phenotype and responds to specific therapies, thereby underlying the importance of distinguishing it from other primary headache syndromes. In this review, the clinical manifestations, differential diagnosis, diagnostic workup and treatment options for this syndrome have been outlined.

Analgesics↗

PubMed2000

Quantitative trait loci for root-penetration ability and root thickness in rice: comparison of genetic backgrounds.

Drought is the major abiotic stress limiting rice (Oryza sativa) production and yield stability in rainfed lowland and upland ecosystems. Root systems play an important role in drought resistance. Incorporation of root selection criteria in drought resistance improvement is difficult due to lack of reliable and efficient screening techniques. Using a wax-petrolatum layer system simulated to compacted soil layers, root traits were evaluated in a doubled haploid (DH) population derived from the cross between 'IR64' and 'Azucena'. Twelve putative QTLs (quantitative trait loci) were detected by interval mapping comprising four QTLs for root-penetration ability, four QTLs for root thickness, two QTLs for penetrated root number, and two QTLs for total root number. These QTLs individually explained 8.4% to 16.4% of the phenotypic variation. No QTL was detected for maximum penetrated root length by interval mapping. One QTL located between RG104 and RG348 was found to influence both root-penetration ability and root thickness. QTLs for root-penetration ability and root thickness were compared across two populations, 'IR64'-'Azucena' and 'CO39'-'Moroberekan', and different testing conditions. The identified consistent QTLs could be used for marker-assisted selection for deep and thick roots with high root-penetration ability in rice.

Oryza↗

PubMed1998

Human pigmentation genetics: the difference is only skin deep.

There is no doubt that visual impressions of body form and color are important in the interactions within and between human communities. Remarkably, it is the levels of just one chemically inert and stable visual pigment known as melanin that is responsible for producing all shades of humankind. Major human genes involved in its formation have been identified largely using a comparative genomics approach and through the molecular analysis of the pigmentary process that occurs within the melanocyte. Three classes of genes have been examined for their contribution to normal human color variation through the production of hypopigmented phenotypes or by genetic association with skin type and hair color. The MSH cell surface receptor and the melanosomal P-protein are the two most obvious candidate genes influencing variation in pigmentation phenotype, and may do so by regulating the levels and activities of the melanogenic enzymes tyrosinase, TRP-1 and TRP-2.

Albinism↗

PubMed2006

Desulfurobacterium atlanticum sp. nov., Desulfurobacterium pacificum sp. nov. and Thermovibrio guaymasensis sp. nov., three thermophilic members of the Desulfurobacteriaceae fam. nov., a deep branching lineage within the Bacteria.

Three thermophilic, anaerobic, strictly chemolithoautotrophic, sulphur- and/or thiosulphate-reducing bacteria, designated SL17(T), SL19(T) and SL22(T), were isolated from deep-sea hydrothermal samples collected at 13 degrees N (East Pacific Rise), Guaymas Basin (Gulf of California) and 23 degrees N (Mid-Atlantic Ridge), respectively. These strains differed in their morphology, temperature range and optimum for growth, energy substrates and 16S rRNA gene sequences. The G+C content of the genomic DNA was 41 mol% (SL22(T)), 42 mol% (SL17(T)) and 46 mol% (SL19(T)). Comparative analysis of phenotypic and phylogenetic traits indicated that strains SL17(T) and SL22(T) represented two novel species of the genus Desulfurobacterium and that strain SL19(T) should be considered as a novel species of the genus Thermovibrio. The names Desulfurobacterium pacificum sp. nov. (type strain SL17(T)=DSM 15522(T)=JCM 12127(T)), Desulfurobacterium atlanticum sp. nov. (type strain SL22(T)=DSM 15668(T)=JCM 12129(T)) and Thermovibrio guaymasensis sp. nov. (type strain SL19(T)=DSM 15521(T)=JCM 12128(T)) are proposed for these organisms. Furthermore, phylogenetic data based on 16S rRNA gene sequence analyses correlated with the significant phenotypic differences between members of the lineage encompassing the genera Desulfurobacterium, Thermovibrio and Balnearium and that of the families Aquificaceae and Hydrogenothermaceae. It is therefore proposed that this lineage represents a new family, Desulfurobacteriaceae fam. nov., within the order Aquificales.

Bacterial Typing Techniques↗

PubMed2026

Identification and in-depth characterization of clinical isolates of Peribacillus frigoritolerans.

UNLABELLED: Peribacillus frigoritolerans is a bacterial species commonly found in the environment and used as a plant-growth promoter and biocontrol agent in agriculture. Recent evidence has proven that Peribacillus spp. are also able to cause severe infections in humans, thus emerging as new human pathogens. In this study, for the first time, 10 P. frigoritolerans strains were isolated from human samples (both superficial and sterile deep body sites) and characterized in terms of morphology, lifestyle, genetics, and virulence. The molecular identification by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing was inconclusive, while whole-genome sequencing was effective in properly identifying isolates within the species P. frigoritolerans. The pangenome analysis provided an overview of the virulence potential of P. frigoritolerans, revealing the presence of genes involved in antibiotic resistance and toxin/exoenzyme production. Phenotypically, the strains displayed different features and behaviors, indicating strain-specific properties and high intra-species variability. A part of the strains exhibited virulence factors, being able to swim and swarm, form biofilms, and produce enzymes and toxins. Antibiotic susceptibility testing revealed resistance to ampicillin for all strains and resistance to erythromycin and clindamycin for some of them. Antimicrobial activity against Gram-positive bacteria and fungi was demonstrated, further corroborating the presence of putative bacteriocin/antimicrobial peptide-encoding genes. An association between the overall virulence potential and infection site/severity was hypothesized. Altogether, these findings highlight the extreme diversity within the species, reveal the strain-dependent pathogenic potential of P. frigoritolerans, and support its role as a candidate human pathogen. IMPORTANCE: This study provides insights into the infectious role of Peribacillus frigoritolerans, an almost unknown bacterial species with agrobiotechnological potential but no history of human infections. This is the first report of P. frigoritolerans isolation from human clinical samples. Ten P. frigorit-olerans strains were herein characterized for their morphology, lifestyle, genetics, and virulence, highlighting an extreme intra-species variability and the potential to act as pathogens in humans. Importantly, this study points out the need for unconventional methods for proper identification of this species, since traditional techniques result inconclusive. Resistance to commonly prescribed antibiotics was also evidenced, confirming the importance of antimicrobial testing on clinical iso-lates. This study lays the foundation for a more in-depth characterization of Peribacillus spp. in the clinical context.

Humans↗

PubMed1999

Expression of anchorin CII (cartilage annexin V) in human young, normal adult, and osteoarthritic cartilage.

In its tissue-specific function as a collagen receptor of chondrocytes, cartilage annexin V (anchorin CII) occupies a key position in the organization of the cell-extracellular matrix (ECM) junction for the tissue. The general role of annexin V (Anx V) in other tissues suggests involvement in cellular secretory processes and in regulation of apoptosis. Immunohistochemical analysis of Anx V in growth plate cartilage, confirmed by in situ hybridization, suggests that Anx V is prominently expressed and forms a major constituent of growth plate chondrocytes. Anx V epitopes are also located in the pericellular matrix of hypertrophic cartilage. In adult articular cartilage the expression is downregulated, with the highest levels of immunostaining found in the upper third of the articular cartilage layers and almost no antigen found in the deep layers. Osteoarthritic (OA) cartilage is characterized by a significant upregulation of message and protein throughout the entire depth of the tissue, an accumulation of cytoplasmic annexin V epitopes, and a release of epitopes into the pericellular and interterritorial matrix, in part co-localized with granular structures. Therefore, Anx V expression and tissue distribution may serve as a histological marker for metabolic alterations and for changes in the cellular phenotype associated with OA.

Adult↗

PubMed1998

Myofibroblastic tumours: an update.

The concept of the myofibroblast is relatively new, since this cell type was defined less than 30 years ago, and there is as yet no firm consensus as to how a myofibroblast should be defined either morphologically or phenotypically. Because its attributes place it midway between a fibroblast and a smooth muscle cell and because it appears capable of functional and phenotypic modulation, some authorities argue that there is no such thing as a truly myofibroblastic tumour. However, since most diagnostic tumour pathology is based on phenotypic features of the excised lesion, it is an unavoidable fact that a wide range of soft tissue tumours show convincing myofibroblastic features. Lesions in this category fall into four main groups--the family of reactive fasciitis-like lesions, a group of benign lesions most of which have been fairly recently recognized (e.g., mammary myofibrolastoma, intranodal myofibroblastoma, angiomyo-fibroblastoma and dermatomyofibroma), the locally aggressive fibromatoses (either superficial or deep) which share features of fibroblasts and myofibroblasts in varying degree and, finally, sarcomas showing myofibroblastic differentiation. These latter include low grade lesions such as so-called infantile fibrosarcoma, inflammatory myofibroblastic tumour and a distinctive form of low grade myofibroblastic sarcoma, as well as some of the high grade lesions formerly known as MFH. Based on the advances made in the past 20 years, it makes no sense to deny the existence of myofibroblastic tumours (especially in an era when histogenetic concepts have crumbled)--instead we need to work towards a reproducible and agreed definition of the myofibroblast.

Child↗

PubMed1983

The neurological mutation staggerer is expressed in embryonic cerebellar transplants matured in the anterior eye chamber of normal mice.

Transplantation of embryonic day 11 cerebellar anlage to the anterior eye chamber of wildtype recipient mice was used to investigate the intrinsic character of the cerebellar mutation staggerer. One phenotypic expression of the staggerer gene in vivo is a postnatal degeneration of cerebellar granule cells. After 43 days of in oculo development cerebellar buds from homozygous staggerer embryos similarly develop into nervous tissues lacking granule cells. On the other hand, transplants of wildtype cerebellar anlagen contain a large population of granule cells. Both the staggerer and wildtype cerebellar transplants had a survival of large neurons, characteristic of Purkinje, Golgi and deep nuclei cells.

Animals↗