Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Variant analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 361 records · Page 20Linked to original sources
PubMed1985

Structure and function of factor IX: defects in haemophilia B.

The genetics of haemophilia B and the structure-function relationships of factor IX interactions with cofactors and substrates have been reviewed. Emphasis has been placed on contributions to our understanding made by analysis of variants. Amino acid substitutions at or near the site of activation lead to inactive factor IX or to factor IX species with decreased clotting activity. Release of the activation peptide is necessary for optimal interaction of factor IX with its cofactors and substrates. Abnormalities in the calcium binding region, whether Gla independent or dependent, also decrease clotting activity. The defects in haemophilia Bm variants somehow affect factor VII-tissue factor interactions with factor X. Other mutations may affect the factor IX heavy chain, probably at or near the active site. Amino acid substitutions may cause conformational changes in factor IX that interfere with other interactions such as with antithrombin III and factor VIII. Recombinant DNA techniques have been employed to analyse normal and abnormal factor IX genes. DNA sequence analysis of factor IX cDNA clones revealed the primary structure of the mature protein and a predicted leader peptide. Knowledge of the primary sequence of factor IX allowed identification of the specific defect in the factor IX Chapel Hill variant. Analysis of normal factor IX genomic clones has determined that the 35 kb gene is composed of eight coding exons and seven intervening sequences. Sequence analysis of the CRM+ variants will identify mutations disrupting the normal interactions of factor IX. Southern analysis of CRM- variants has revealed gross factor IX gene deletions in some cases. Such deletions have been employed for carrier deletion in some families. Restriction fragment length polymorphisms in the factor IX gene have also proven useful for carrier identification. Manipulations of the cloned factor IX gene to make specific mutations in vitro and improvements in the technology for expression of deliberately modified genes will further elucidate the relationships between factor IX structure and function.

Amino Acid Sequence↗
PubMed1990

Phenotypic and molecular biological analysis of human butyrylcholinesterase variants.

Our laboratory has recently shown that several variant forms of human butyrylcholinesterase, associated with unusual sensitivity to succinylcholine, are caused by specific mutations within the structural DNA coding for this enzyme. Atypical (dibucaine-resistant) butyrylcholinesterase is caused by a point mutation at nucleotide position 209(GAT-- greater than GGT), which changes aspartate 70 to glycine. One fluoride-resistant variant family has a point mutation at nucleotide 728(ACG-- greater than ATG), which changes threonine 243 to methionine. Another type of fluoride-resistant variant has a point mutation at nucleotide 1169(GGT-- greater than GTT), which changes glycine 390 to valine. One type of silent phenotype is due to a frame-shift mutation at nucleotide position 351(GGT-- greater than GGAG). A polymorphic site at nucleotide position 1615 (GCA/ACA), coding for Ala/Thr, accounts for the quantitative K-variant, which causes an approximate one-third reduction of activity, if Thr occupies that position at codon 539. Examples are given to illustrate the advantages of using a combination of the new DNA analytical techniques, including: the use of allele-specific probes, with the standard serum cholinesterase phenotyping methods. More accurate typing of patients with certain variants is now possible; pedigree analysis will be aided by the improved methodology.

Alleles↗
PubMed2025

Dissecting the shared genetic architecture of schizophrenia with ventricular subregion volumes.

Schizophrenia is characterized by cerebral ventricular enlargement as an early and consistent structural anomaly. While genetic factors significantly influence both schizophrenia and cerebral ventricular enlargement, the shared genetic etiology between them requires further investigation. Using summary statistics from recent large genome-wide association studies on schizophrenia and 9 ventricular subregion volumes phenotypes. Gaussian causal mixture modeling was applied to characterize the genetic architecture and overlap between schizophrenia and ventricular subregion volumes phenotypes. Local genetic correlation was investigated with Local Analysis of Variant Association. The conjunctional false discovery rate framework was used to identify the specific shared genetic loci, annotated with FUMA. Gaussian causal mixture modeling estimated schizophrenia to be more polygenic more polygenic (9574 trait-influencing variants) than ventricular subregion volumes phenotypes (157-1267 trait-influencing variants). Conjunctional false discovery rate analysis identified 42 shared genetic loci, 17 loci were identified as novel for both schizophrenia and the ventricular subregion volumes phenotypes. Local Analysis of Variant Association revealed that 11 distinct loci demonstrated significant differences, among which 4 loci were situated in the Major Histocompatibility Complex region. Annotated genes in shared loci were enriched in molecular signaling pathways involved in inflammation and the brain structure. The shared loci between them were annotated and enriched in Major Histocompatibility Complex and inflammation-related pathways, highlighting new opportunities for future investigation.

Schizophrenia↗
PubMed1994

Structural analysis of two length variants of the rDNA intergenic spacer from Eruca sativa.

Restriction enzyme analysis of the rRNA genes of Eruca sativa indicated the presence of many length variants within a single plant and also between different cultivars which is unusual for most crucifers studied so far. Two length variants of the rDNA intergenic spacer (IGS) from a single individual E. sativa (cv. Itsa) plant were cloned and characterized. The complete nucleotide sequences of both the variants (3 kb and 4 kb) were determined. The intergenic spacer contains three families of tandemly repeated DNA sequences denoted as A, B and C. However, the long (4 kb) variant shows the presence of an additional repeat, denoted as D, which is a duplication of a 224 bp sequence just upstream of the putative transcription initiation site. Repeat units belonging to the three different families (A, B and C) were in the size range of 22 to 30 bp. Such short repeat elements are present in the IGS of most of the crucifers analysed so far. Sequence analysis of the variants (3 kb and 4 kb) revealed that the length heterogeneity of the spacer is located at three different regions and is due to the varying copy numbers of repeat units belonging to families A and B. Length variation of the spacer is also due to the presence of a large duplication (D repeats) in the 4 kb variant which is absent in the 3 kb variant. The putative transcription initiation site was identified by comparisons with the rDNA sequences from other plant species.

Base Sequence↗
PubMed1994

Dual-color detection of DNA sequence variants by ligase-mediated analysis.

Genetic screening for sequence variants associated with disease is assuming increasing importance in clinical medicine as well as in research. We describe an efficient method for such analyses, comprising a combination of practical features: (1) Amplified DNA samples are analyzed for their ability to serve as templates in standardized allele-specific ligation reactions between oligonucleotide probes; (2) Two allele-specific probes, differentially labeled with either of two lanthanide labels, compete for ligation to a third oligonucleotide (the signal from the two labeled probes can thus be directly compared in a sensitive time-resolved fluorescence detection reaction); and (3) Large sets of analyses are processed in parallel using a 96-pin capture manifold, serving to reduce pipetting steps and the risk of contamination. We present here the basis of the technique and its application to the screening for two common mutations causing cystic fibrosis and alpha 1-antiytrypsin deficiency.

Base Sequence↗
PubMedDate not supplied

[Nucleotide sequence of gag and env genes of human immunodeficiency virus type 1, found in Russia: detection of new recombinant variants].

Phylogenetic analysis of nucleotide sequences of gag and env genes of type 1 human immunodeficiency virus (HIV-1) variants isolated from individuals infected through sexual intercourse or nosocomially (by injections with nonsterile syringes) showed that 5 of 27 (18.5%) isolated strains were recombinants. Two viruses found in the Russian Far East had gagAenvE genotype, three other recombinants had envG genotype; gag gene of one isolate belonged to subtype A and gag genes of two others belonged to subtype D. Detection of new recombinant variants in addition to the A/B recombinant described previously shows that these viruses can contribute to the HIV-1 genetic variability in Russia.

Female↗
PubMed2001

Analysis of two genomic variants of orang-utan hepadnavirus and their relationship to other primate hepatitis B-like viruses.

We recently described orang-utan hepadnavirus (OuHV) (Warren et al., Journal of Virology, 73, 7860-7865, 1999). Phylogenetic analyses indicated that the various isolates of OuHV can be divided into two genomic variants. Two representatives from each genomic cluster were analysed both molecularly and phylogenetically. Their genome organization was highly similar to other hepadnaviruses of apes and humans. The complete genome sequences of the two OuHV types had an overall 5% sequence difference. Research on 25 seropositive Bornean orang-utans showed that, of the 19 animals infected with one variant, 12 originated from East Kalimantan. Phylogenetic analysis was performed using the full-length genomes of various primate hepadnaviruses. The tree topology revealed one cluster of Old World hepadnaviruses that is divided into two subclusters, one consisting of the ape viruses, and the other comprising the human genotypes A-E. These data suggest that the great apes and gibbons have been infected with a common ancestor hepadnavirus.

Animals↗
PubMed2026

Parkinson Disease Pathogenic Variants: Cross-Ancestry Analysis and Microarray Data Validation.

BACKGROUND AND OBJECTIVES: Known pathogenic variants (PVs) in Parkinson disease (PD) contribute to disease development but have yet to be fully explored by arrays on a large scale. This study evaluated genotyping success of the NeuroBooster array (NBA) and determined the frequencies of PVs across ancestries. METHODS: We analyzed the presence and allele frequency of PVs in 28,710 PD cases, 9,614 other neurodegenerative disorder cases, and 15,821 controls across 11 ancestries within the Global Parkinson's Genetics Program (GP2) data set. Cluster plots were used to assess the quality of PVs genotyped on NBA. RESULTS: Genes previously predicted to have high or very high confidence of causing PD tend to have more PVs and are present across ancestry groups. Of 34 known PD gene PVs assessed, 25 were typed by NBA and classified as "good" (n = 12), "medium" (n = 4), or "bad" (n = 9) quality variants. DISCUSSION: Our results confirm the likelihood that established PD genes are pathogenic and highlight the importance of ancestrally diverse research in PD. We also show the usefulness of the NBA as a reliable tool for the genotyping of rare variants of PD.

Journal Article↗
PubMed1990

Classification of glucose-6-phosphate dehydrogenase variants by multivariate statistical analysis.

Using principal component analysis a two-dimensional presentation of kinetic parameters from various G6PD-variants was obtained from which similarities between individual enzymes became detectable. Conclusions could be drawn as to how far the kinetic parameters contribute to the discrimination between different variants. An objective classification of G6PD-variants was achieved by application of cluster analysis. The proposed methods provide an effective means for differential elucidation of G6PD-variants and other heterogeneous enzymopathies.

Cluster Analysis↗
PubMed1989

Analysis of isotype switch variants of a Qa-5 specific hybridoma.

Qa-5 is a Class I MHC Ag expressed on mature T cells and natural killer (NK) cells of mice, and is defined by specific reactivity with an IgM secreting hybridoma (B16-167). The availability of IgG antibodies with Qa-5 specificity would greatly facilitate in vivo studies of Qa-5 positive NK cells. Using a sequential subline technique in conjunction with ELISA screening, several isotype variants of the B16-167 parent line were selected and cloned. An IgG2a, an IgG2b, and two IgG1 switch variants were selected, and it was demonstrated that one of these cloned lines produced both IgM and IgG1 simultaneously. Binding of the variant antibodies to Qa-5+ cells was not detected by flow cytometry analysis, nor by the ability to deplete NK activity from Qa-5+ large granular lymphocytes (LGL). However, all of the variant lines appeared to use the same VH region genes by Southern blot analysis. Furthermore, IgG2a from the switch variants inhibited binding of the parental IgM anti-Qa-5 when used in excess, and reduction of the parental IgM anti-Qa-5 to monomeric form abolished its binding capacity. These data together indicate that the weak binding by the IgG variants may be due to loss of an innate low affinity/high avidity binding of the parent IgM. Therefore, the isotype switch detection procedure is a useful technique for selection of antibodies with various effector functions, provided the initial antibody is an antibody with sufficient binding affinity.

Alkylation↗
PubMed1999

Germline mutations in the multiple endocrine neoplasia type 1 gene: evidence for frequent splicing defects.

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome characterized by parathyroid hyperplasia, pituitary adenomas, and neuroendocrine tumors of the pancreas and duodenum. In 1997, the MEN1 tumor suppressor gene was identified, and numerous germline mutations have been reported to be distributed throughout the gene. We used single strand conformational variant (SSCV) analysis to search for germline mutations in the members of 33 kindreds with a confirmed diagnosis of MEN 1. SSCV analysis revealed 25 conformational variants representing germline mutations that are predicted to result in loss of normal menin function. Twenty different disease-associated mutations were identified: five resulting in potential abnormal RNA splicing, two missense mutations, seven nonsense mutations, and six frameshift mutations. The aberrant splice products were identified and confirmed by RT-PCR and direct sequence analysis for two of the five splice mutations. Sixteen of the 20 (80%) mutations identified have not been previously reported. Mutations were not identified in eight kindreds with signs and symptoms consistent with MEN 1. The SSCV analysis revealed mutations in 76% (25 of 33) of the kindreds investigated, thus showing SSCV analysis to be a reliable mutation detection strategy. One-fifth of the mutations identified in this study involve intron sequences, therefore, highlighting the importance of including intron sequences in the search for germline mutations in the MEN1 gene. The need to investigate the entire gene when characterizing new MEN 1 families presents challenges in the translation of genetic studies to efficient clinical diagnostic tests.

Chromosomes, Human, Pair 11↗
PubMed1995

Latent phenotype analysis of three deletion variants of herpes simplex virus type 1 (HSV-1) in mouse model.

Latency analysis of three herpes simplex virus type 1 (HSV-I) strain 17 syn+ deletion variants (1704, 1705 and 1706) showed that they established, maintained and reactivated from latency. The kinetics of reactivation of 1705 and 1706 were similar to the parent HSV-1, 17 syn+, in which reactivation occurred 5-6 days post-explanation, but 1704 reactivated with delayed kinetics i.e. on the 12th day post-explantation. Since 1704 has deleted both copies of the latency associated transcripts (LATs) promoter region and one copy of the LAT coding region in internal inverted repeat sequence of long region (IRL), it was concluded that the LATs play a part in latency reactivation of 1704 from dorsal root ganglia (DRG) of spinal cord in mouse model. Restoration of the deleted sequences in the variant 1704 by marker rescue with the wild type BamHI b fragment resulted in a wild type genotype. This virus was designated as 1704R. Latency studies of 1704R revealed that the rate and frequency of reactivation was intermediate between 17 syn+ and 1704, suggesting a secondary undetected mutation affecting latency phenotype. Isolation of 1704LP-, during the same marker rescue experiment in which both copies of promoter region of the LAT are deleted and reactivation of this virus from latency with delayed kinetics confirms that the LATs play a role in reactivation from latency.

Amino Acid Sequence↗
PubMed1998

Intraindividual and interspecies variation in the 5S rDNA of coregonid fish.

This study was designed to characterize further the nontranscribed intergenic spacers (NTSs) of the 5S rRNA genes of fish and evaluate this marker as a tool for comparative studies. Two members of the closely related North American Great Lakes cisco species complex (Coregonus artedi and C. zenithicus) were chosen for comparison. Fluorescence in situ hybridization found the ciscoes to have a single multicopy 5S locus located in a C band-positive region of the largest submetacentric chromosome. The entire NTS was amplified from the two species by polymerase chain reaction with oligonucleotide primers anchored in the conserved 5S coding region. Complete sequences were determined for 25 clones from four individuals representing two discrete NTS length variants. Sequence analysis found the length variants to result from presence of a 130-bp direct repeat. No two sequences from a single fish were identical. Examination of sequence from the coding region revealed two types of 5S genes in addition to pseudogenes. This suggests the presence of both somatic and germline (oocyte) forms of the 5S gene in the genome of Coregonus. The amount of variation present among NTS sequences indicates that accumulation of variation (mutation) is greater in this multicopy gene than is gene conversion (homogenization). The high level of sequence variation makes the 5S NTS an inappropriate DNA sequence for comparisons of closely related taxa.

Animals↗
PubMed1994

Immunoglobulin somatic variation; studies of receptor editing in a human B cell lymphoma.

In order to study mechanisms of immunoglobulin somatic variation in committed immunoglobulin (Ig) expressing B cells, we used the fluorescent activated cell sorter to isolate rare variants from a surface Ig positive (sIg+) diffuse large cell B lymphoma cell line (mu lambda+). These variants were either negative for sIg expression (sIg-) or expressed sIg which differed from the original parental tumor cell line, both in idiotypes and Ig lambda isotypes (sIg+Id-). In the following report we review the results from the studies of these variants. DNA analysis showed that all variants had new Ig lambda gene rearrangements, which had occurred either on a previously excluded allele, or on the productively rearranged allele of the parental cell line. The sIg- variants, which had undergone nonfunctional Ig lambda rearrangements on the expressed parental allele, and thereby deleted the productive rearrangement, continued to functionally rearrange the same allele and regenerated sIg expression. While the parental cell line expressed low levels of the recombination activating genes, RAG1 and RAG2, expression of these genes were considerably upregulated in both the immunoglobulin negative and the idiotypic variants. Somatic immunoglobulin V gene hypermutation did not contribute to the observed immunoglobulin somatic variation. These results demonstrate that, through differential expression of the RAG genes, sIg+ B cells are able to somatically alter their sIg receptors through secondary Ig lambda gene rearrangements. This mechanism may allow B cells with non-selectable, or auto-reactive, antigen receptors to alter these receptors (receptor editing). Ongoing Ig gene rearrangement may limit the usefulness of immunotherapeutic approaches directed at the antigen receptor in some diffuse large cell lymphomas.

Amino Acid Sequence↗
PubMed1978

Principal clinical features and prognosis in chronic lymphocytic leukemia.

A prospective study of 102 patients with chronic lymphocytic leukaemia (CLL) on 30 parameters subdivided into 77 variables was analyzed by correspondence analysis, a variant of principal component analysis, which allows simultaneous graphical representation of patients and variables. This statistical method clearly defined three principal clinical features recognized at the time of diagnosis: lymph node proliferation, lymphoid infiltration and cytopenia. Cytopenia was clearly subdivided into peripheral and central types. Each of these clinical features were derived from clinical and laboratory observations which agreed with each other. Simple examination permitted an evaluation of these three syndromes. They seemed to be independent of each other except for a relationship between central cytopenia and lymphoid infiltration. Thus clinical staging at the moment of diagnosis must record three scales of severity corresponding to the three independant clinical features. Prognosis was essentially related to cytopenia, whatever the mechanism. In a further analysis of the subsequent progress of the disease, a "common path" for patients was found terminating in a region of the graph where marked splenomegaly and cytopenia were plotted. We conclude that it is necessary to consider the three clinical features independently in a clinical staging. This study emphasizes the poor prognosis of cytopenia and splenomegaly and indicates that follow up and treatment should take this feature into account.

Anemia↗
PubMed1977

Correspondence analysis of HLA gene frequency data from 124 population samples.

Correspondence analysis, a variant of principal components analysis, is used to interpret and compare gene frequencies of the HLA system for 124 samples from different populations studied in the Fifth and Sixth International Histocompatibility Workshops. The major advantage of this analysis is that populations and HLA genes are represented simultaneously with respect to the same axes in multidimensional space. This permits the visual interpretation of genetic differences between populations, the relative participation of each gene in the dispersion, and the correspondence between populations and genes. By this method a clear separation of ethnic groups in the world is obtained. Furthermore, within Europe the separation of samples from different countries is concordant with their geographical distances. The HLA system appears sufficiently polymorphic to define a population by its gene frequencies.

Asian People↗
PubMed2026

Comparative genomics of the monophasic variant of Salmonella Typhimurium: analysis of Colombian genomes and their relationship with international lineages.

The monophasic variant of Salmonella enterica serovar Typhimurium (STVM) represents a growing threat to global public health owing to its wide dissemination, capacity to adapt to multiple hosts, and antimicrobial resistance. In this study, 98 STVM isolates recovered in Colombia (57 from humans and 41 from pig farms and abattoirs) were genomically characterized between 2015 and 2022 and compared with 102 representative genomes of international lineages by whole-genome sequencing (WGS) and phylogenomic analysis. Phylogenomic analysis revealed the existence of two well-defined endemic lineages in Colombia (Clusters 1 and 2), arising from independent introduction events and subsequent local stabilization. Both lineages comprise isolates of human and swine origin without clear phylogenetic separation by host species, suggesting active zoonotic cocirculation and closely integrated interspecies transmission dynamics. Marked differences were observed in the accessory genome, including the differential presence of prophages (e.g., Gifsy-2, Fels-2, SW9), virulence plasmids, and resistance profiles. The Colombian lineages exhibited a high frequency of the pSTV plasmid (85%, n = 84/98) and a substantial burden of resistance determinants to quinolones (such as qnrB19, 74.5%; gyrA S83F mutation, 19.4%), phenicols (floR), tetracyclines (tetA, tetB), β-lactams (blaTEM-1B), and heavy metals. In contrast, the Colombian genomes clustered with the European ST34 lineage lacked pSTV but retained resistance and heavy metal operons. These findings demonstrate that international and endemic lineages coexist in Colombia with independent evolutionary trajectories, underscoring the need to strengthen genomic surveillance under the "One Health" approach to anticipate emerging threats and develop integrated control strategies.IMPORTANCEThe monophasic variant of Salmonella Typhimurium (STVM) has emerged as a predominant serovar in both humans and swine internationally. In Colombia, a fundamental question driving this study was whether local isolates belonged to international lineages or represented endemic strains. This study provides the first comprehensive genomic characterization demonstrating that two Colombian endemic lineages circulate simultaneously between humans and pigs without phylogenetic separation by host species, confirming active zoonotic transmission. The results demonstrate the coexistence of both lineages, each with distinctive repertoires of mobile genetic elements and specific antimicrobial resistance profiles. Understanding these transmission dynamics and evolutionary patterns is crucial for public health, as it demonstrates how zoonotic pathogens can establish locally adapted lineages with distinct resistance patterns. The genomic evidence of sustained interspecies circulation highlights the critical need for integrated surveillance strategies under the "One Health" framework. This will enable anticipating emerging threats, tracing transmission routes, and developing targeted interventions in food production systems.

One Health↗