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 181 records · Page 10Linked to original sources

PubMed1977

Antibody response to the streptococcal group A-variant polysaccharide in BASILEA rabbits lacking kappa-polypeptide chains.

Rabbits from a variant strain called BASILEA, in which homozygotes express only lambda-type chains and heterozygotes have normal kappa/lambda ratios, were hyperimmunized with a streptococcal group A variant vaccine. Homozygotes (bas/bas) produced antibodies with lambda-chains, heterozygotes, however, produced predominantly antibodies with kappa-chains. The incidence of restricted high responders in the BASILEA strain was high; it was probably introduced by the original mutant rather than by the loss of kappa-chains (founder effect). The degree of heterogeneity of homozygotes is similar to the heterogeneity of heterozygotes, and to that of rabbits expressing kappa-chains. This suggests that in the rabbit, the repertoire of lambda-chain genes is of similar size to that of kappa-chain genes.

Animals↗

PubMed1977

Application of isoelectric focusing in alpha1-antitrypsin phenotyping.

alpha1-Antitrypsin, the major protease inhibitor in human serum, occurs in a considerable number of variant forms, some of which are associated with lung and liver diseases. The identification of these genetic variants, generally called Pi-types, by means of isoelectric focusing is described, as well as investigations concerning the practical application of isoelectric focusing as a routine procedure for typing the variants of alpha1-antitrypsin. Finally, isoelectric focusing is compared with the most widely used Pi-phenotyping technique, namely acid starch-gel electrophoresis followed by immunoelectrophoresis in antibody-containing agarose gel.

Genetic Variation↗

PubMed1995

Significance of the highly conserved Gly-4 residue in human cystatin A.

The expression system for human recombinant cystatin A has already been established to be a fusion protein with porcine adenylate kinase in Escherichia coli [Kaji et al. (1990) Biol. Chem. Hoppe-Seyler 371, Suppl., 145-150]. After cyanogen bromide cleavage of the fused protein expressed in E. coli, the cystatin portion could be readily isolated. The inhibitory activity of the obtained variant (Cyst A (2-98)) was found to be almost identical with that of the wild type, and thereafter a mutation was introduced into this variant (Ctst A(2-98)), called the standard variant. To elucidate the role of the Gly-4 residue, which is completely conserved in all cystatin species, this residue was substituted with 17 other amino acids by means of cassette mutagenesis. Thus 17 variants (Cyst A(2-98)[G4X]) obtained were examined as to their inhibitory activity towards papain. As the side chain of the substituted amino acid residue became more bulky, the inhibitory activity of the variant markedly decreased. Variants whose side chains were bulkier than a Val residue showed almost no inhibitory effect towards papain. Consequently, it was deduced that the large side chain of a substituted amino acid may cause steric hindrance, which may be responsible for the decrease in inhibitory activity. Thus, we could conclude that the 4th (Gly) residue on cystatin A must be small, because amino acids which existed on the N-terminal side of this residue could interact with a papain molecule.

Amino Acid Sequence↗

PubMed1981

Distribution and respiratory properties of sheep hemoglobins A and B containing the II alphaHis chain.

We recently reported the discovery of a second alpha chain, differing from the common alpha chain by the replacement 113 (or 114) Leucine leads to Histidine, in the hemoglobin of several domestic sheep. The ratio of the common alpha chain, here called alpha Leu, to the variant one, here called II alpha His, was either about 1.8:1 or about 4:1. In this study, the distribution of the II alpha His chain in 217 sheep from 8 domestic breeds was investigated: the II alpha His chain is present in 30% of animals from different breeds. Oxygen equilibrium determination showed no differences in the oxygen affinity, the Bohr effect and the heme-heme interaction of Hb A (alpha 2 beta 2A) and Hb B (alpha 2 beta 2B), each containing one of the three possible alpha chain phenotypes.

Animals↗

PubMed1998

Molecular characterization of immunoglobulin G4 gene isoallotypes.

The molecular bases of classical serological immunoglobulin allotypes are progressively uncovered through detailed characterization of the relevant genes. Here we describe two isoallotypic determinants of the G4 gene. In the first, Leu 309, as in G1 and G3, is changed to Val, as in G2; studies on myeloma proteins have long assigned the immunologically defined nG4 m(a)/(b) to the same position. The two molecular variants, here called IGHG4*L309 and IGHG4*V309, are allelic in IGHC haplotypes with a single G4 gene, but can be found together in cis in G4-duplicated haplotypes. A second isoallotypic variant was found at codon 409, where either Arg, as in G1 and G3, or Lys, as in G2, can be found. Both isoallotypes are associated with several 'silent isoallotypic' substitutions dispersed through the hinge, CH2 and CH3 domains. This suggests segmental gene conversion as the common mechanism of origin.

Base Sequence↗

PubMed1986

Characterization of fibrinogen Milano I: amino acid exchange gamma 330 Asp----Val impairs fibrin polymerization.

An abnormal fibrinogen was found in two asymptomatic members (father and daughter) of the same family, originating from northern Italy. Routine coagulation studies revealed prolonged thrombin and reptilase clotting times. Plasma fibrinogen levels, as determined by a functional assay, were markedly diminished, whereas the heat precipitation method indicated normal fibrinogen values. On the basis of these findings, a tentative diagnosis of dysfibrinogenemia was made, and according to the accepted nomenclature, this fibrinogen variant was called "fibrinogen Milano l." The time course of fibrinopeptide A and B release from fibrinogen Milano l was normal, but the aggregation of fibrin monomers was delayed. Two-dimensional electrophoresis of reduced variant fibrinogen chains showed a defective gamma-chain with increased cathodic mobility. An abnormal electrophoretic mobility was observed also for the gamma-chain remnants of fibrinogen fragments D1 and D2 derived from fibrinogen Milano l, whereas the charge anomaly was lost after a further digestion by plasmin to D3, suggesting that the structure abnormality of this variant is situated in the region gamma 303-356. An abnormal peptide was isolated after cyanogen bromide cleavage of intact fibrinogen Milano l. This fragment spans from position gamma 311 to gamma 336. Amino acid analysis of the abnormal peptide showed the presence of valine and a diminished content of aspartic acid. Sequence analysis demonstrated an amino acid exchange Asp----Val in the gamma-chain at position 330.

Adult↗

PubMed1995

The chromo shadow domain, a second chromo domain in heterochromatin-binding protein 1, HP1.

The chromo domain was originally identified as a protein sequence motif common to the Drosophila chromatin proteins, Polycomb (Pc) and heterochromatin protein 1 [HP1; Paro and Hogness (1991) Proc. Natl. Acad. Sci. USA, 88, 263-267; Paro (1990) Trends Genet., 6, 416-421]. Here we describe a second chromo domain-like motif in HP1. Subsequent refined searches identified further examples of this chromo domain variant which all occur in proteins that also have an N-terminally located chromo domain. Due to its relatedness to the chromo domain, and its occurrence in proteins that also have a classical chromo domain, we call the variant the 'chromo shadow domain'. Chromo domain-containing proteins can therefore be divided into two classes depending on the presence, for example in HP1, or absence, for example in Pc, of the chromo shadow domain. We have also found examples of proteins which have two classical chromo domains. The Schizosaccharomyces pombe SWI6 protein, involved in repression of the silent mating-type loci, is a member of the chromo shadow group. The similar modular architecture of SpSW16, HP1 and HP1-like proteins supports the model that the specificity of action of chromatin proteins is generated by combinations of protein modules.

Amino Acid Sequence↗

PubMed1989

So-called membranocystic lesion (MCL)--a new variant of ceroid type lipopigment.

Structures very close morphologically to the so-called membranocystic formations of the Nasu-Hakola's disease and identical in histochemical properties with them were found in several other metabolically unrelated conditions such as cerebrotendinous xanthomatosis (perivascularly in the brain) and in human atheromatous plaques. This with some other literary data points to unspecific nature of the membranocystic lesion (MCL) which also has been resisting satisfactory classification in terms of pathobiochemistry. Evidence is presented suggesting the MCL is lipopigment in nature. This is based on its lipid histochemical properties dominated by prominent autofluorescence and marked sudanophilia resistant to lipid extraction procedures. Ultrastructural pattern of the MCL was membranous, being dominated by mostly individual trilaminar membranes about 15 nm thick which could be also occasionally identified in various intralysosomal ceroid type lipopigments. It is supposed that the MCL lipopigment is formed mainly extracellularly from the lipid rich debris.

Arteriosclerosis↗

PubMed1995

Human cystatin A is inactivated by engineered truncation. The NH2-terminal region of the cysteine proteinase inhibitor is essential for expression of its inhibitory activity.

A series of NH2-terminal truncated forms of human cysteine proteinase inhibitor, cystatin A, was prepared by genetic engineering using Escherichia coli harboring mutated genes. Each variant of cystatin A was efficiently expressed as a fused protein with porcine adenylate kinase and released by CNBr degradation after exchange of the sole inner Met to Leu. The mutant cystatin A lacking an amino-terminal Met residue (called standard variant starting from Ile2, CystA2-98(M65L) showed the same inhibitory activity as authentic one isolated from human epidermis. Two-residue truncation scarcely influenced the activity, but further truncations deleting Pro3 and beyond conservative Gly4 and Gly5 caused a remarkable decrease of their inhibitory activity. But little effect was observed by a substitution of Pro3 with Leu. The loss of the activity by amino-terminal truncation was compensated slightly by engineered substitution of Gly75 with His on a second loop. In the two-dimensional 15N-1H HSQC NMR spectrum, four-residue truncation was found to cause changes in the chemical shifts of Val47 and Val48, which locate on a first loop and consist of a conservative QVVAG sequence. Furthermore, the truncation led to a change in fluorescence spectroscopic behavior of Trp75, which was introduced as a probe on the second loop. Fluorescence intensity of the Trp of the truncated (5-98) form was more affected by heating than the active standard variant. Conversely, fluorescence of Trp75 in 2-98 form was more quenched by acrylamide than the 5-98 variant. Thus, the amino-terminal region of cystatin A is essential for the expression of its inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1998

Blastic variant of mantle-cell lymphoma: cytomorphologic, immunocytochemical, and molecular genetic features of tissue obtained by fine-needle aspiration biopsy.

Mantel-cell lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma that has a moderately aggressive clinical course, generally between that a low-grade and intermediate-grade lymphomas. However, a small subset of MCLs, the so-called "blastic" variant, exhibits a poor prognosis and an aggressive clinical course. We describe a case of blastic MCL that occurred in a 64-yr-old man and that was diagnosed and accurately subclassified as blastic MCL on the basis of an fine-needle aspiration (FNA) biopsy. The aspirate smears showed a monotonous population of intermediate-sized lymphocytes with irregular nuclear contours, finely dispersed nuclear chromatin, and inconspicuous nucleoli. Material was obtained by FNA for ancillary studies (immunocytochemical stains, flow cytometry, cytogenetics, image analysis, and molecular studies) that supported the diagnosis of blastic MCL. Surgical biopsy confirmed the diagnosis. These findings underscore the utility of FNA in diagnosing lymphomas, particularly when the cytomorphologic examination is combined with appropriate ancillary studies.

Biopsy, Needle↗

PubMed1999

An in situ hybridization study of the distribution of the GABA(B2) protein mRNA in the rat CNS.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system. GABA exerts its actions through two classes of receptors: GABA(A), multimeric ligand-gated Cl(-) ion channels (a class which has been proposed to include the homomeric variant previously called GABA(C), to be designated GABA(A0r)); and GABA(B), G-protein coupled receptors which regulate Ca(2+) and K(+) channels. Currently, within the GABA(B) receptor family two proteins have been identified through molecular cloning techniques and designated GABA(B1) and GABA(B2). Two N-terminal variants of GABA(B1) were isolated and designated GABA(B1a) and GABA(B1b). The distribution of neurons in the rat CNS expressing the mRNA for the GABA(B1) isoforms have been previously described by in situ hybridization histochemistry. The recent isolation and identification of the GABA(B2) protein by homology cloning has enabled the use of radiolabeled oligonucleotides to detect the distribution of the expression of GABA(B2) mRNA in the rat CNS. The expression of GABA(B2) mRNA was observed to be primarily related to neuronal profiles. The highest levels of GABA(B2) mRNA expression were detected in the piriform cortex, hippocampus, and medial habenula. GABA(B2) mRNA was abundant in all layers of the cerebral cortex, the thalamus and in cerebellar Purkinje cells. Moderate expression was observed in several hypothalamic and brainstem nuclei. In contrast to the distribution of GABA(B1) mRNA, only a weak hybridization signal for GABA(B2) was detected over cells of the basal ganglia, including the caudate-putamen, nucleus accumbens, olfactory tubercle and throughout most of the hypothalamus. Moderate-to-heavy GABA(B2) mRNA expression was also seen over dorsal root and trigeminal ganglion cells. In general, the pattern of GABA(B2) mRNA expression in the rat brain overlaps considerably with the distributions described for both GABA(B1) mRNAs, and is concordant with the distribution described for GABA(B) receptor binding sites. However, differences between GABA(B2) expression levels and GABA(B) binding sites were observed in the basal ganglia.

Animals↗

PubMed1997

Testosterone levels and evoked vocal responses in a natural population of the frog Batrachyla taeniata.

Relationships between testosterone plasma levels and evoked vocal responses of males of the leptodactylid frog Batrachyla taeniata from southern Chile were studied. Evoked vocal responses were elicited in the field with playbacks of a synthetic imitation of the conspecific advertisement call and variants of this signal for which different temporal parameters were modified. Testosterone plasma levels were measured with radioimmunoassay in blood samples obtained from the experimental subjects immediately after the playback experiments and from nonstimulated males. Testosterone levels between groups did not differ significantly. A significant correlation between testosterone concentration and number of calls given in response to the synthetic advertisement call was found. Testosterone levels were also significantly correlated with the total number of calls given by the experimental subjects in response to the complete series of stimuli. Other measures of evoked vocal responses, i.e., number of pulses per call, call duration, pulse rate, and latency to first call, were not significantly correlated with testosterone levels. These results indicate a predominant effect of testosterone on the motivation of males of B. taeniata to call, rather than on the physical attributes of the vocalizations.

Animals↗

PubMed1982

Genetic variants of the Bombyx mori silkworn encoding sericin proteins of different lengths.

A variant sericin polypeptide originally found by acid gel electrophoresis in the Nd-s mutant strain of the silkworm, Bombyx mori, has been analyzed genetically. The variant polypeptide (called S-2v) is encoded by a gene which behaves as a codominant allele of the gene encoding the standard S-2 sericin polypeptide. Linkage analysis locates these alleles at 0.0 map unit on chromosome 11. SDS-polyacrylamide gel electrophoresis shows that the molecular weight of the S-2v variant polypeptide is lower by approximately 62,500 than that of the S-2 polypeptide. Amino acid analysis indicates that the two sericin polypeptides have similar compositions. These results are consistent with the idea that the variant allele arose by deletion within the S-2 coding sequence in the Src-2 gene locus as the result of unequal recombination.

Amino Acids↗

PubMed1986

The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. III. Coordinate alterations in viral gp70 antigen expression and restoration of CTL-susceptibility to insusceptible variant tumors.

Two variant subclones, called cl.18-5 and cl.18-12, were derived from the AKR.H-2bSL1 tumor cell line that were, in contrast to the parental cells, selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL). Cell surface expression of viral envelope (env) and group-specific antigens (gag) on these CTL-resistant variants were analyzed and compared with the expression of these antigens on AKR.H-2bSL1 and two other CTL-susceptible clones, cl.1 and cl.5, also derived from AKR.H-2bSL1. Although normal levels of gag-encoded and H-2 antigens were displayed on the CTL-resistant variants, the expression of five distinct determinants of viral gp70 antigen as defined by monoclonal antibodies was significantly decreased on these CTL-resistant variants relative to their expression on the CTL-susceptible cell lines. However, similar dramatic changes in cell surface gp70 antigen expression were undetectable as defined by anti-gp70-specific antiserum. Immunoprecipitation and gel electrophoretic analysis revealed that gp70 molecules from cl.18-5 cells had a lower m.w. than those of AKR.H-2bSL1, but there were no differences in the m.w. of gp70 antigens from AKR.H-2bSL1, cl.5, and cl.18-12 cells. Expression of the five gp70 antigenic determinants mentioned above was completely restored by exposure of cl.18-5 and cl.18-12 cells to the halogenated pyrimidine, iododeoxyuridine (IudR). Treatment of cl.18-5 and cl.18-12 cells with IudR simultaneously restored CTL susceptibility of these cells to anti-AKR/Gross virus CTL without affecting gag and H-2 antigen expression. Viral gp70 antigen immunoprecipitated from IudR-treated cl.18-5 cells had a mobility slightly lower, but different from that of untreated cl.18-5 cells. Pulse-labeling with [35S]-methionine showed that IudR treatment of cl.18-5 cells caused the expression of an additional high m.w. gp70 precursor protein originally absent in untreated cl.18-5 cells but present on parental AKR.H-2bSL1 cells. Collectively, these results pointed to the involvement of viral gp70 antigenic determinants in the recognition of AKR/Gross virus-induced tumor targets by anti-AKR/Gross virus CTL.

AKR murine leukemia virus↗

PubMed1978

Reversion in variants from a duplication strain of Aspergillus nidulans.

Strains of Aspergillus nidulans with a chromosome segment in duplicate, one in normal position and one translocated to another chromosome, are unstable at mitosis. In addition to variants which result from deletions in either of the duplicate segments, which usually have improved morphology, they produce variants with deteriorated morphology. Three deteriorated variants reverted frequently to parental type morphology, both spontaneously and after ultra-violet treatment. Of six reversions analysed genetically, five were due to suppressors and one was probably due to back mutation. The suppressors segregated as single genes and were not linked to the mutation which they suppress. The instability of these so-called "deteriorate"variants is discussed in relation to mitotic instability phenomena in A. nidulans.

Aspergillus nidulans↗

PubMed2026

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

Humans↗

PubMed1988

[Squamous cell carcinoma with a sarcomatoid variant of the vagina].

A case of squamous cell carcinoma with a sarcomatoid variant, usually called a spindle cell carcinoma, located in the vagina of a postmenopausal woman is reported. Although a cytologic examination of a smear of the scraped tumor showed the coexistence of sarcomatous spindle and keratinizing carcinomatous cells, the first bioptic specimen consisted only of sarcomatous tissue. Further histologic, immunohistochemical and ultrastructural examinations succeeded in making a definite diagnosis of a squamous cell carcinoma with a sarcomatoid variant. We would like to emphasize that combined cytologic and histologic examinations led us to make a correct diagnosis after discussing the differential diagnosis.

Aged↗

PubMed1995

[Variant gap phenomenon in A-V conduction].

In 361 consecutive patients 4 with variant gap phenomenon (VGP) underwent intracardiac electrophysiological studies. The premature atrial response initially delayed in His-Purkinje system (HPS) which had a long relative refractory period (RRP), and H-V interval was prolonged. However, as atrial responses were more premature, the atrioventricular node (AVN) showed RRP and slowed down the conduction, that made HPS get rid of RRP before the response arriving. Thus the conduction resumed, and H-V interval became normal. It was different from the classic gap phenomenon. We call it variant gap phenomenon.

Adult↗