SEARCH · Search PubMed

Results for “Variant calling”

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 847 records · Page 47Linked to original sources

PubMed2000

[Left bundle branch block. Electrocardiographic and prognostic aspects].

The concept of left bundle branch block (LBBB) was recognised at the beginning of the 20th century but confusion, due to the extrapolation data from animal experimentation, persisted for many years between the electrocardiographic appearances of LBBB and right bundle branch block (RBBB). The typical appearances of LBBB are now well known and consist of: 1) increased duration of the QRS complex > 0.12 seconds; 2) a wide, exclusive R wave with a plateau or notched summit in the left precordial leads and usually in D1 and aVL; 3) an important delay in the intrinsecoid deflection in the left precordial leads (0.08 to 0.12 seconds after the onset of QRS); 4) an axis of repolarisation opposite that of the QRS complex with so-called "secondary" abnormalities. The authors emphasise that some electrocardiographic variants carry a poor prognosis, in particular those with major QRS axis deviation to the left or, much less commonly, to the right. The diagnosis of left ventricular hypertrophy is possible in cases of LBBB by using the criteria of QRS amplitude in the left precordial leads. On the other hand, the diagnosis of myocardial infarction is more difficult, the criteria being very specific but having a sensitivity < 50%. The deleterious effects of LBBB on the haemodynamics are well known but their study has become a new firld of research since the introduction of bi-ventricular pacing for the treatment of cardiac failure. In dilated cardiomyopathy, LBBB increases the duration of functional mitral regurgitation and decreases left ventricular filling times. The prognostic implications of LBBB have been the object of many studies: the reports in the literature indicate a large increase in mortality when LBBB develops in patients over 44 years of age. The progression to complete atrioventricular block is common only when the HV interval exceeds 100 ms. In other cases, the prophylactic implantation of a cardiac pacemaker does not improve the prognosis which depends on the severity of the underlying cardiac disease.

Bundle-Branch Block↗

PubMed2002

Fast phylogenetic methods for the analysis of genome rearrangement data: an empirical study.

Evolution operates on whole genomes through mutations that change the order and strandedness of genes within the genomes. Thus analyses of gene-order data present new opportunities for discoveries about deep evolutionary events, provided that sufficiently accurate methods can be developed to reconstruct evolutionary trees. In this paper we present two new methods of character coding for parsimony-based analysis of genomic rearrangements: one called MPBE-2, and a new parsimony-based method which we call MPME (based on an encoding of Bryant), both variants of the MPBE method. We then conduct computer simulations to compare this class of methods to distance-based methods (NJ under various distance measures). Our empirical results show that two of our new methods return highly accurate estimates of the true tree, outperforming the other methods significantly, especially when close to saturation.

Animals↗

PubMedDate not supplied

[Mesenteric lymphangiomas of the small intestine in children].

The authors have made an analysis of 15 cases with lymphangiomas of the small intestine mesentery in children aged from 3 days up to 12 years. Attention is called to problems in diagnosing this pathology. The optimum variant of examination is presented which allow the correct diagnosis to be made. All the children were operated upon. The method was chosen depending on localization of the cyst and on the patient's age. Good results of treatment were obtained.

Child↗

PubMed2004

Vascular anatomy of the radius and ulna diaphyses in their reconstructive surgery.

The vascular factor in the unsuccessful healing of the osteotomised forearm bone is widely discussed in literature at the so-called "level operations" aiming at correcting the "ulna minus" variant in Kienböck's disease. The purpose of our study was to trace the nourishing vessels of the forearm bones from their source from which a. nutritia radii (ANR) and a. nutritia ulnae (ANU) is separated and to locate the foramen nutritium (FN) of the radial and ulnar bones diaphysis. The forearms of 70 upper extremities were dissected and 204 macerated radial bones and 134 macerated ulnar bones were investigated scopically and metrically. The results demonstrated that there is less variability of sources from which ANR was separated as compared to the variability of the sources from which ANU was separated. Foramen nutritium radii (FNR) and foramen nutritium ulnae (FNU) were located mainly along facies anterior and its edges margo anterior and margo interosseus and only in a few cases they were observed along facies posterior. The metrical investigations showed that FNR were located mainly in the second fourth along the bone length, between 30 and 40% from the radial bone length in the distal direction. FNU were located mainly in the second fourth along the bone length, between 30 and 50% from the ulnar bone length in the distal direction. The results for vascular anatomy of the forearm bones give grounds to assume that osteotomy with a subsequent shortening of the radius is more feasible than osteotomy with ulnar lengthening. The distal half of the radius, between the third and fourth quarter in particular, is also recommended as most suitable for surgical intervention.

Aged↗

PubMed2005

[Cystic hypersecretory carcinoma: rare and potentially aggressive variant of intraductal carcinoma of the breast. Report of five cases].

OBJECTIVE: To describe a poorly recognized histological and immunohistochemical features of cystic hypersecretory carcinoma of breast, including the overexpression of HER-2/neu protein and androgen receptors. SUBJECT: Review of clinical and pathological features of 5 cases of cystic hypersecretory carcinoma. SETTING: Private Bioptic Lab, Plzen and Department of Pathology, Charles University, Plzen. SUBJECT AND METHODS: Five cases of rare variant of intraductal carcinoma of the breast, so-called cystic hypersecretory carcinoma, are reported. The patients were females aged between 53 and 78 years (average 66.8 years). The size of the lesions ranged between 7 and 8 cm in largest dimension. RESULTS: In two cases, the development of high grade invasive ductal carcinoma was observed; in one additional case there was recurrence of high grade in situ carcinoma after three years. Strong overexpression of HER-2/neu protein was observed in three cases including those two with invasive component. Protein p53 was variably positive in all cases. Steroid receptor immunohistochemical study yielded variable results with only one case being positive for both estrogen and progesterone receptors. Interestingly, in most case (4/5) staining for androgen receptors was observed. CONCLUSION: The importance of correct diagnosis of this potentially aggressive lesion is emphasized. The differential diagnosis of breast lesions with predominantly cystic growth pattern is discussed in detail.

Aged↗

PubMed1990

[Trigeminal neuralgia associated with primitive trigeminal artery: report of two cases].

Two cases of trigeminal neuralgia associated with the primitive trigeminal artery are reported. From 1981, the authors have treated 131 trigeminal neuralgia patients with microvascular decompression. Among them, we encountered two rare cases of trigeminal neuralgia associated with the primitive trigeminal artery (PTA) and its variant (PTAV). Case 1 is a 74-year-old woman who was admitted to our hospital due to pain of maxilla and mandible. We diagnosed her pain as trigeminal neuralgia. Preoperative angiogram showed the primitive trigeminal artery arising from the cavernous portion of the right internal carotid artery (ICA). She underwent a microvascular decompression operation. We found that her right trigeminal nerve was compressed by the right superior cerebellar artery (SCA) and the right anterior inferior cerebellar artery (AICA). We transferred the offending arteries, and her pain disappeared. Case 2 is a 48-year-old man who was admitted to our hospital due to severe mandibular pain. We diagnosed his pain as trigeminal neuralgia, and he underwent a microvascular decompression operation. His left trigeminal nerve was found compressed by the left SCA and the AICA, and the AICA was arising from the direction of Meckel's cave. His severe pain disappeared completely after operation. Postoperative angiogram of his left ICA showed an aberrant artery arising from the cavernous portion of the ICA, to the region of the left AICA. This aberrant artery is a variant of PTA (PTAV). PTA and PTAV, the so called persistent congenital arteries, are said to accompany aneurysms and other vascular lesions, and affect hemodynamic stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1988

Cystic hypersecretory duct carcinoma of the breast. Report of a case with fine-needle aspiration.

A patient with a recently described rare histologic variant of ductal carcinoma of the breast, so-called cystic hypersecretory duct carcinoma, is described. The findings on fine-needle aspiration biopsy, and to our knowledge, the first cytologic study of this entity reported in the literature, are described and differentiated from mucinous carcinoma and benign mucocelelike lesions. The histologic differential diagnosis, with an emphasis on benign lesions that may have a predominant cystic component, is also discussed.

Aged↗

PubMed2005

Comprehensive statistical study of 452 BRCA1 missense substitutions with classification of eight recurrent substitutions as neutral.

BACKGROUND: Genetic testing for hereditary cancer syndromes contributes to the medical management of patients who may be at increased risk of one or more cancers. BRCA1 and BRCA2 testing for hereditary breast and ovarian cancer is one such widely used test. However, clinical testing methods with high sensitivity for deleterious mutations in these genes also detect many unclassified variants, primarily missense substitutions. METHODS: We developed an extension of the Grantham difference, called A-GVGD, to score missense substitutions against the range of variation present at their position in a multiple sequence alignment. Combining two methods, co-occurrence of unclassified variants with clearly deleterious mutations and A-GVGD, we analysed most of the missense substitutions observed in BRCA1. RESULTS: A-GVGD was able to resolve known neutral and deleterious missense substitutions into distinct sets. Additionally, eight previously unclassified BRCA1 missense substitutions observed in trans with one or more deleterious mutations, and within the cross-species range of variation observed at their position in the protein, are now classified as neutral. DISCUSSION: The methods combined here can classify as neutral about 50% of missense substitutions that have been observed with two or more clearly deleterious mutations. Furthermore, odds ratios estimated for sets of substitutions grouped by A-GVGD scores are consistent with the hypothesis that most unclassified substitutions that are within the cross-species range of variation at their position in BRCA1 are also neutral. For most of these, clinical reclassification will require integrated application of other methods such as pooled family histories, segregation analysis, or validated functional assay.

Amino Acid Sequence↗

PubMed2002

Melanotrichoblastoma: immunohistochemical study of a variant of pigmented trichoblastoma.

Trichoblastomas (TBs) are benign skin tumors recapitulating the differentiation of hair follicles. Several pathologic variants have been described, including the rare pigmented TB. We report a deeply pigmented nodular tumor excised on the scalp of a 32-year-old African woman, which was clinically suggestive of blue nevus or melanoma. Histologically, the tumor presented features of TB, remarkable by virtue of heavy melanin deposits found within and around tumor nests. By immunohistochemistry, abundant dendritic melanocytes with features of hair follicle melanocytes (expression of S100 protein, tyrosinase, and, most importantly, gp100/HMB-45) were found within the tumor masses. By analogy with melanoacanthoma, a tumor consisting of a combined proliferation of epidermal keratinocytes and melanocytes, we called this tumor "melanotrichoblastoma" and view it as a peculiar variant of (pigmented) TB.

Adult↗

PubMed1999

Interaction of the putative androgen receptor-specific coactivator ARA70/ELE1alpha with multiple steroid receptors and identification of an internally deleted ELE1beta isoform.

Steroid-regulated gene transcription requires the coordinate physical and functional interaction of hormone receptors, basal transcription factors, and transcriptional coactivators. In this context ARA70, previously called RFG and ELE1, has been described as a putative coactivator that specifically enhances the activity of the androgen receptor (AR) but not that of the glucocorticoid receptor (GR), the progesterone receptor, or the estrogen receptor (ER). Here we describe the cloning of the cDNA for ELE1/ARA70 by RT-PCR from RNA derived from different cell lines (HeLa, DU-145, and LNCaP). In accordance with the previously described sequence, we obtained a 1845-bp PCR product for the HeLa and the LNCaP RNA. Starting from T-47D RNA, however, an 860-bp PCR product was obtained. This shorter variant results from an internal 985-bp deletion and is called ELE1beta; accordingly, the longer isoform is referred to as ELE1alpha. The deduced amino acid sequence of ELE1alpha, but not that of ELE1beta, differs at specific positions from the one previously published by others, suggesting that these two proteins are encoded by different nonallelic genes. ELE1alpha is expressed in the three prostate-derived cell lines examined (PC-3, DU-145, and LNCaP), and this expression is not altered by androgen treatment. Of all rat tissues examined, ELE1alpha expression is highest in the testis. This is also the only tissue in which we could demonstrate ELE1beta expression. Both ELE1alpha and ELE1beta interact in vitro with the AR, but also with the GR and the ER, in a ligand-independent way. Overexpression of either ELE1 isoform in DU-145, HeLa, or COS cells had only minor effects on the transcriptional activity of the human AR. ELE1alpha has no intrinsic transcription activation domain or histone acetyltransferase activity, but it does interact with another histone acetyltransferase, p/CAF, and the basal transcription factor TFIIB. The interaction with the AR occurs through the ligand-binding domain and involves the region corresponding to the predicted helix 3. Mutation in this domain of leucine 712 to arginine greatly reduces the affinity of the AR for ELE1alpha but has only moderate effects on its transcriptional activity. Taken together, we have identified two isoforms of the putative coactivator ARA70/ELE1 that may act as a bridging factor between steroid receptors and components of the transcription initiation complex but which lack some fundamental properties of a classic nuclear receptor coactivator. Further experiments will be required to highlight the in vivo role of ELE1 in nuclear receptor functioning.

Acetyltransferases↗

PubMed1988

Coexpression of epithelial membrane antigen (EMA), Ki-1, and interleukin-2 receptor by anaplastic large cell lymphomas. Diagnostic value in so-called malignant histiocytosis.

A group of 63 cases of anaplastic large cell lymphomas (variants of diffuse large cell lymphomas often diagnosed as "malignant histiocytosis") was characterized on both morphologic criteria and expression of epithelial membrane antigen (EMA) and Ki-1 antigen (CD30). On the basis of the reactivity of these tumors with anti-EMA and anti-Ki-1 antibodies, four subtypes could be distinguished. In the majority of cases (n = 49), neoplastic cells coexpressed EMA and Ki-1 antigens. Nineteen of these cases were tested for IL-2R, and all were positive (Type I, EMA+, Ki-1+, IL-2R+). In the second group (n = 5), the neoplastic cells expressed EMA but not the Ki-1 antigen. These cases were not tested for the presence of IL-2R (Type II, EMA+, Ki-1-, IL-2R?). There were tumors with similar morphology expressing only Ki-1 antigen (Type III, EMA-, Ki-1+, IL-2R-) or negative for both EMA and Ki-1 antigens (Type IV, EMA-, Ki-1-, IL-2R-). EMA appeared to occur predominantly on activated cells, as has been previously shown for Ki-1 antigen. Analysis using monoclonal antibodies to T-cell, B-cell, or macrophage-associated differentiation antigens showed that these tumors were heterogeneous in terms of cell lineage. Tumors coexpressing EMA, Ki-1, and IL-2R (Type I), were most commonly of T-cell origin (n = 12); the remainder in this type expressed B-cell markers (n = 4), a mixed B/T phenotype (n = 2), or no clear phenotype (n = 9). By contrast, tumors of Types II, III, and IV were mainly from B-cell origin (n = 6) or showed a mixed B/T phenotype (n = 1). Despite the fact that a significant proportion of these cases were initially classified morphologically as "malignant histiocytosis," only 3 of the 63 cases were possibly of histiocytic origin. These results confirm that true malignant histiocytosis is rare and that most tumors with histologic features currently regarded as being consistent with this diagnosis are lymphocytic in origin and express activation antigens such as EMA, Ki-1 antigen, and IL-2R.

Antibodies↗

PubMed2002

Genetics of insulin resistance.

Insulin resistance, defined as the decreased ability of insulin to perform its biological functions, is likely to represent the primary physiologic defect underlying the insulin resistance syndrome (IRS), which includes insulin resistance/hyperinsulinemia, glucose intolerance and/or type 2 diabetes mellitus, visceral obesity, hypertension, and dyslipidemia. This constellation of traits is a leading cause of cardiovascular mortality and morbidity. Insulin sensitivity varies widely among individuals. Although environmental provocations including physical inactivity and caloric excess play an important role in the development of obesity and thus insulin resistance, epidemiologic and family studies show that there are also moderate genetic influences on the development of insulin resistance. Extreme forms of insulin resistance may be caused rarely by mutations in the genes for the insulin receptor and peroxisome proliferator-activated receptor gamma. However, the genetic basis for common more moderate forms of insulin resistance is likely to be polygenic and heterogeneous. Evidence further suggests that gene variants may have phenotypic influences on more than one IRS trait (so-called pleiotrophy), which may explain, in part, the clustering of these traits. This article reviews the evidence that insulin resistance has a genetic basis. Progress to date toward identifying specific gene variants are reviewed. Ultimately, the identification of specific gene variants that influence insulin resistance and other IRS traits will have profound influences on our understanding of the molecular and pathophysiologic basis of these disorders, from which new and more effective preventive and therapeutic interventions will be possible.

Chromosomes, Human, Pair 19↗

PubMed1999

EBNA-1 gene sequences in Brazilian and American patients with Hodgkin's disease.

We examined the types of Epstein-Barr virus-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal mutations occurring in Hodgkin's disease (HD) and reactive tissues from two different geographic regions. Previously reported EBNA-1 C-terminal region amino acid sequence variants, based on the amino acid at codon 487, include Prototype (P)-ala, which is found in the B95.8-derived prototype virus, P-thr, Variant (V)-leu, V-val, and V-pro. Using polymerase chain reaction (PCR) to amplify portions of the EBNA-1 gene, followed by DNA sequencing, we found a single EBNA-1 gene sequence variant in each tissue, whether reactive or neoplastic and whether from Brazil or the United States. Variant EBNA-1 gene sequences were more common in both neoplastic and non-neoplastic tissues from different geographic areas than the so-called prototype sequence. In the 17 Brazilian HD cases, 4 cases had P-thr variants and 13 had V-leu variants. In the six reactive tissues from Brazil, one had a P-ala variant, two had P-thr variants, and three had V-leu variants. In the 12 American HD cases, 2 had P-ala variants, 6 had P-thr variants, and 4 had V-leu variants. The 11 American reactive tissues included 2 P-ala variants, 5 P-thr variants, and 4 V-leu variants. In both countries, there were similar variant EBNA-1 sequences present in normal tissues and HD cases. Compared with the P-ala and P-thr cases, the V-leu cases were more likely to have the 30-bp latent membrane protein 1 (LMP1) gene deletion (P = 0.0075). In addition, cases of HD with the V-leu were statistically associated with a substitution of asparagine for glutamine at codon 322 of the C-terminal portion of the LMP1 gene. Our results suggest that any variation in EBNA-1 gene sequence is caused by a polymorphism present in pre-existing viral strains in the underlying population, and not a mutation occurring during oncogenesis.

Brazil↗

PubMed2025

Backtracking Cell Phylogenies in the Human Brain with Somatic Mosaic Variants.

Somatic mosaic variants, and especially somatic single nucleotide variants (sSNVs), occur in progenitor cells in the developing human brain frequently enough to provide permanent, unique, and cumulative markers of cell divisions and clones. Here, we describe an experimental workflow to perform lineage studies in the human brain using somatic variants. The workflow consists in two major steps: (1) sSNV calling through whole-genome sequencing (WGS) of bulk (non-single-cell) DNA extracted from human fresh-frozen tissue biopsies, and (2) sSNV validation and cell phylogeny deciphering through single nuclei whole-genome amplification (WGA) followed by targeted sequencing of sSNV loci.

Humans↗

PubMed2005

Regulation of adenylate cyclase type VIII splice variants by acute and chronic Gi/o-coupled receptor activation.

We previously reported that acute agonist activation of G(i/o)-coupled receptors inhibits adenylate cyclase (AC) type VIII activity, whereas agonist withdrawal following chronic activation of these receptors induces AC-VIII superactivation. Three splice variants of AC-VIII have been identified, which are called AC-VIII-A, -B and -C (with AC-VIII-B missing the glycosylation domain and AC-VIII-C lacking most of the C1b area). We report here that AC-VIII-A and -B, but not -C, are inhibited by acute mu-opioid and dopaminergic type D2 receptor activation, indicating that the C1b area of AC-VIII has an important role in AC inhibition by G(i/o)-coupled receptor activation. On the other hand the glycosylation sites in AC-VIII did not play a role in AC-VIII regulation. Although AC-VIII-A and -C differed in their capacity to be inhibited by acute agonist exposure, agonist withdrawal after prolonged treatment led to a similar superactivation of all three splice variants, with no significant change in AC-VIII expression. AC-VIII superactivation was not affected by pre-incubation with a cell permeable cAMP analogue, indicating that the superactivation does not depend on the agonist-induced reduction in cAMP levels. The superactivated AC-VIII-A, -B and -C were similarly re-inhibited by re-application of agonist (morphine or quinpirole), returning the activity to control levels. These results demonstrate marked differences in the agonist inhibition of the AC-VIII splice variants before, but not after, superactivation.

Adenylyl Cyclases↗

PubMed2005

Expression and function of variants of slob, slowpoke channel binding protein, in Drosophila.

Slob binds to and modulates the Drosophila Slowpoke (dSlo) calcium-activated potassium channel and also recruits the ubiquitous signaling protein 14-3-3 to the channel regulatory complex. RT-PCR reveals the presence of multiple slob transcripts in Drosophila heads. The transcripts are predicted to encode proteins that we call Slob51 (kDa), Slob57, Slob65, and Slob71. Slob51 and Slob65 are splice variants that lack a motif important for the binding of 14-3-3. Previous microarray analyses demonstrated the circadian cycling of slob mRNA, and we show by quantitative PCR that more than one transcript cycles in fly heads. Using in situ hybridization, we observe differences in the expression patterns of the different transcripts. Immunohistochemistry on Drosophila heads reveals Slob71/65 protein to be enriched in the lateral neurons, in contrast to Slob57/51 protein, which is expressed most prominently in the pars intercerebralis neurons and dorsal giant interneurons. Using a heterologous expression system, we show that different Slobs bind to different extents to dSlo and 14-3-3. These data reveal an unexpected diversity of the dSlo/Slob/14-3-3 dynamic regulatory complex.

14-3-3 Proteins↗

PubMed1992

Epithelial and mixed hepatoblastoma in the adult. Histological observations and general considerations.

Two instances of hepatoblastoma in adults are reported, with one case representing a purely epithelial, the other a mixed epithelio-mesenchymal variant. The purely epithelial tumour, consisting entirely of so-called fetal elements, was present in the liver of a 35-year-old woman without any other hepatic changes, whereas the mixed tumour developed in the coarsely nodular liver of a 73-year-old man with a currently inactive cirrhosis. Besides the epithelial component, this case held predominantly indifferent spindle-shaped and histiocytic mesenchymal cells which frequently gave rise to osteoid and to bony trabeculae, and on occasion also to vascular structures, biliary ducts and even to groups of hepatocytes. The cytological and histological picture of both cases is comparable even in its details to that seen in the hepatoblastomas of early childhood. This concordance should be insisted upon as a diagnostic pre-condition if a mixed tumour in the adult, consisting of several components, is to be accepted as a hepatoblastoma. This similarity also enables us to recognize the purely epithelial variant of the hepatoblastoma in the older patient as belonging to this tumour category, and to separate it from other hepatic carcinomas. It is suggested that in these tumours the pluripotent cells, or the cells that have again become pluripotent, are derived from differentiated hepatocytes; no evidence in favour of the existence of a particular cellular subpopulation or of "stem cells" has been found.

Adult↗

PubMed1992

[Measurements and variations in the region of the optic canal. CT and anatomy].

This investigation of the optic canal is based on measurements of 60 macerated adult European skulls from the Alexander-Ecker Collection at the Anatomy Department of the University of Freiburg. An indian skull is also described, in which the cranial end of the left optic canal is closed by a bony plate. Computer tomographical and anatomical measurements were compared in order to assess the correlation of the two methods of investigation and the accuracy of the CT representation of osseous structures. The coronal projection of the optic canal proved to be optimal for CT examination--the sections meet the optic canal at an angle of 85.5 degrees. The measurements of transverse diameters correlate poorly, whereas vertical diameters and distances correlate well. The extent to which anatomical variations can be assessed by CT was also investigated. All anatomical variants could be observed in coronal sections, except the bony lamina in the Indian skull, which could not be seen until a contrast medium was used. The so-called "keyhole anomaly" appeared in 3.3% in our material, the "figure-of-eight" variant in 2.5%, and a carotid clinoid canal in 13.3%.

Adult↗