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Results for “Variant identification”

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At least 19 recordsLinked to original sources

PubMed2026

Novel genetic variants identification and immune profiling in ataxia telangiectasia patients.

BACKGROUND: Ataxia telangiectasia (AT) is an autosomal recessive neurodegenerative disease. While heterozygous relatives of AT patients are known to be clinically healthy, a predisposition to various pathologies has been reported. Our aim was firstly, to further characterize the clinical features and broaden the spectrum of genetic pathogenic variants in AT patients. Secondly, we aimed to study the immune profiles of AT patients and their relatives to identify similarities or common biomarkers. METHODS: A Target Gene Sequencing for six patients suspected with AT was performed. Computational analysis was conducted to assess the pathogenicity of novel variants. The distribution of immune cells was assessed by flow cytometry in patients with AT, AT-like disorder, Friedreich ataxia, and in AT relatives. The expression pattern of candidate genes was evaluated by RT-qPCR. RESULTS: We identified and predicted the pathogenicity of novel variants in the ATM gene. Computational analysis suggested that the novel identified missense mutation could affect ATP binding pattern and ATM protein flexibility, while Alu element insertion could probably induces a premature stop codon. Furthermore, our results confirm the pathogenic effect of identified splicing mutations on the ATM transcript. Moreover, we noticed a high percentage of LTCD4 + and LTCD8 + senescent subsets in AT patients and a relative increase of the of intermediate and non-classical monocytes accompanied with a decrease of classical monocytes specifically in AT patients with truncated biallelic mutations which was intriguingly similar to the immune profile of AT parents. In addition, a difference of immune pattern was observed between AT patients with biallelic truncated mutations compared to those with at least one non-truncated mutation, with a variability intragroup. Gene expression analysis identified FOXO3, IL33 and METTL3 as putative genes that may yield clues into AT pathogenesis. CONCLUSION: Taken together, our study expands the mutational spectrum of AT disease worldwide and further characterize the immune profile of AT patients uncovering a possible difference in some immune cellular subsets related to ATM mutation type and delineate putative immune abnormalities related to ATM heterozygosity among AT parents. Furthermore, dysregulation in FOXO3, IL33 and METTL3 expression could be related to disease severity.

Humans↗

PubMed2026

Lineage-associated small inversions disrupt dosT, dnaE2, and a promoter-adjacent region in some Mycobacterium tuberculosis isolates.

UNLABELLED: Large molecular inversions in the genome of Mycobacterium tuberculosis (Mtb) due to factors like the presence of insertion sequences and transposases are widely known. However, smaller inversions within coding sequences and non-coding control elements are rarely reported. The present study aims to identify inversions and their potential impact on Mtb biology in a lineage-specific manner. Structural variants (SVs) could only be detected by long reads. For this, we simulated long reads by de novo assembling the short-read sequencing data sets and subsequently aligned representative strains from each lineage using the Progressive Mauve algorithm. Independently, long-read sequencing from the Pacific Biosciences platform was acquired and analyzed using the structural variant identification method. Variants were merged, and Fisher's exact test was carried out to identify the inversion association with lineages. To visualize deoxyribonucleic acid (DNA) features, the DNA-features-viewer tool was used. Simulated reads from short-read sequencing gave indications of lineage (L)-specific inversions. The long-read sequencing approach led to the identification of seven unique inversions: two positively associated with L1, one positively associated with L3, two negatively associated with L4, and two positively associated with L3 but negatively associated with L4 (P < 0.05). The inversions encompassed primarily non-essential genes like sdaA, dosT, Rv2026c, dnaE2, Rv1341, Rv1342, and lprD. An interesting inversion was observed in the upstream control element of purB and Rv0776c. The study sheds light on small inversions that may be causing alterations in expression, formation of fusion genes, and nonsense mutations that may have a role in lineage-specific phenotypic changes. IMPORTANCE: The role of mutations like SNPs and INDELs and their association with drug resistance is well known in Mycobacterium tuberculosis (Mtb). However, structural variations, especially inversions, are largely overlooked and unreported. In this paper, publicly available whole-genome sequencing datasets from Illumina and Pacific Biosciences-Oxford Nanopore Technologies platform have been used to detect inversions and report seven unreported Mtb lineage-specific small inversions.

Mycobacterium tuberculosis↗

PubMed1992

Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver, epithelial and endothelial cells. Structurally, it has similarities to kringle-containing serine proteases, although it does not possess proteolytic activity. A structure-activity relationship study of human HGF was performed by functional analysis of HGF substitution and deletion variants. Analysis of HGF variants was accomplished by defining their ability to induce DNA synthesis on hepatocytes in primary culture and to compete with wild-type HGF for binding to a soluble form of the HGF receptor. Three groups of variants were made: (i) substitutions at the cleavage site, (ii) substitutions within the protease-like domain and (iii) deletions of the beta-chain and/or kringle domains. Our results show that: (i) single-chain HGF is a zymogen-like promitogen in that cleavage into a two-chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity; (ii) certain mutations in the protease-like domain result in variants that are completely defective for mitogenic activity, yet exhibit apparent receptor binding affinities similar to wild-type HGF (Kd approximately 50-70 pM); and (iii) a variant containing the N-terminal 272 residues of mature HGF showed only a 4-fold increase in Kd when compared with wild-type HGF indicating that a primary receptor binding determinant is located within this sequence.

Animals↗

PubMed1991

Identification of variant apolipoprotein E by isoelectric focusing and restriction isotyping in a patient with type III hyperlipoproteinemia.

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Apolipoprotein E2↗

PubMed1976

[Mathematical express interpretation of the results of biochemical typing for identification of representatives of Enterobacteriaceae].

With the aid of Ypapi-14A computer the authors studied the sets of biochemical tests to assess the differential significance of each of the tests in identification of representative of the Enterobactericeae family. The sequence of the tests under study in the order of interpriorty by the differential significance was determined. The test sets providing the best identification variants were demonstrated. Complete identification of enterobacteriae was possible in all the cases with the use of 6 to 9 tests.

Bacteriological Techniques↗

PubMed1975

[Transferrin variants: significance and identification in paternity cases (author's transl)].

Transferrin phenotypes were determined in 3380 sera of unrelated persons of the western region of Germany with 97.60 percent for TfC and 2.40 percent for Tf variants. Identification was achieved by immunochemical means or through autoradiography. Relative mobilities in some variants were measured using Tf B2C (0.7) as reference. Application of Tf variants is demonstrated in paternity cases.

Clostridium perfringens↗

PubMed2024

ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers.

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER. Using specifically designed mosaic and tumorized genomes for the analysis of recall and precision across somatic SNVs, insertions or deletions (indels), and structural variants (SVs), we demonstrate that ONCOLINER is capable of improving and harmonizing genome analysis across three state-of-the-art variant discovery pipelines in genomic oncology.

Humans↗

PubMed2025

Cycle threshold values and SARS-CoV-2 variant associations with breakthrough infections: a retrospective study in Accra, Ghana.

BACKGROUND: Breakthrough infections are defined as SARS-CoV-2 infections occurring ≥ 14 days after completing the primary COVID-19 vaccination series and remain a public health challenge, particularly in regions where immune-evasive variants are circulating. However, data on their virological and clinical profiles in low-resource settings are limited. METHODS: This retrospective study was conducted from July to December 2022 in Accra, Ghana, among individuals testing positive for SARS-CoV-2. Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) was performed using the Allplex™ 2019-nCoV Assay. Cycle threshold (Ct) values for the nucleocapsid (N), RNA-dependent RNA polymerase (RdRP), and envelope (E) genes, categorised as < 25, 25–30, or > 30. Variant identification targeted Alpha, Delta, and Omicron mutations using mutation-specific RT-PCR. Logistic regression was used to assess associations between vaccination status and demographic, clinical, and virological factors. RESULTS: Of the 268 samples analysed, 81 tested positive; 43.20% [n = 35] were vaccinated individuals. Median Ct-values for the N [27.13, IQR: 21.59–31.96] and E [24.57, IQR: 19.43–29.43] genes were significantly higher among vaccinated cases, indicating lower viral loads. Breakthrough infections were strongly associated with the Omicron variant [aOR = 4.38, p = 0.034]. Diarrhoea [aOR = 9.67, p = 0.022], sore throat [aOR = 8.99, p = 0.038], headache [aOR = 10.156, p = 0.039] and chills [aOR = 3.316, p = 0.046] were mostly associated with breakthrough infections. Ct-values of 25–30 [aOR = 11.33, p = 0.012] and > 30 [aOR = 4.01, p = 0.047] were significantly associated with breakthrough infection compared to Ct < 25 in breakthrough infections. CONCLUSION: Vaccinated individuals with SARS-CoV-2 infection had lower viral loads and were more likely to be infected with the Omicron variant. These findings reinforce the role of vaccination in reducing viral load and support the adoption of practical surveillance strategies, such as Ct value-based surveillance and variant screening in low middle-income countries facing similar constraints in genomic capacity and vaccine deployment.

Humans↗

PubMed2025

CAKL: Commutative algebra k-mer learning of genomics.

Despite the availability of various sequence analysis models, comparative genomic analysis remains a challenge in genomics, genetics, and phylogenetics. Commutative algebra, a fundamental tool in algebraic geometry and number theory, has rarely been used in data and biological sciences. In this study, we introduce commutative algebra k-mer learning (CAKL) as the first-ever nonlinear algebraic framework for analyzing genomic sequences. CAKL bridges between commutative algebra, algebraic topology, combinatorics, and machine learning to establish a new mathematical paradigm for comparative genomic analysis. We evaluate its effectiveness on three tasks-genetic variant identification, phylogenetic tree analysis, and viral genome classification-typically requiring alignment-based, alignment-free, and machine-learning approaches, respectively. Across eleven datasets, CAKL outperforms five state-of-the-art sequence analysis methods, particularly in viral classification, and maintains stable predictive accuracy as dataset size increases, underscoring its scalability and robustness. This work ushers in a new era in commutative algebraic data analysis and learning.

Journal Article↗

PubMed1992

The identification of a variant form of cystathionine beta-synthase in nematodes.

Characterization of the physical and catalytic properties of the enzyme responsible for nematode "activated L-serine sulfhydrase" activity (L-cysteine + R-SH-->cysteine thioether + H2S) has led to its identification as a novel, variant form (allelozyme) of cystathionine beta-synthase that is distinct from a mammalian-type synthase also present in nematodes. Additional work has demonstrated the ability of live Panagrellus redivivus to produce H2[35S] from exogenous L-[35S]cysteine and 2-mercaptoethanol, thus providing preliminary evidence for the in vivo operation of the activated L-serine sulfhydrase reaction in nematodes.

Animals↗

PubMed2025

Identification of intragenic variants in pediatric patients with intellectual disability in Peru.

BACKGROUND: Intellectual disability in Latin America can reach a frequency of 12% of the population, these may include nutritional deficiencies, exposure to toxic or infectious agents, and the lack of universal neonatal screening programs. In 90% of patients with intellectual disability, the etiology can be attributed to variants in the genome. OBJECTIVE: to determine intragenic variants in patients with intellectual disability between 5 and 18 years old at Instituto Nacional de Salud del Niño. METHODS: It is a descriptive cross-sectional study with convenience sampling. A total of 124 children diagnosed with intellectual disability were selected based on psychological test results and availability for whole exome sequencing. In addition, a chromosomal analysis of 6.55 M was performed on ten patients with a negative result in sequencing. Relative and absolute frequencies and measures of central tendency and dispersion were determined according to their nature. In addition, multiple linear regression and Poisson regression were used to determine the association between some clinical characteristics and the probability of occurrence in patients with positive results. RESULTS: The median age of the patients was 6.3 (IQR = 5.95), males accounted for 57.3%, and 91.9% of the cases had mild intellectual disability. Exome sequencing determined the etiology in 30.6% of patients with intellectual disability, of which 52.6% were autosomal dominant inheritance. The most frequent genes found were MECP2, STXBP1 and LAMA2. A broad genotype-phenotype correlation was identified, highlighting the genetic heterogeneity of intellectual disability in this population. The presence of dermatologic lesions, dystonia, peripheral neurological disorders, and fourth finger flexion limitation were observed more frequently in patients with intellectual disability with "positive results". CONCLUSIONS: This study shows that one-third of patients with intellectual disability exhibit intragenic variants, highlighting the importance of genetic analysis for accurate diagnosis. The identification of genes such as MECP2, STXBP1, and LAMA2 underscores the genetic heterogeneity of intellectual disability in the studied population. These findings emphasize the need for genetic testing in clinical management and the implementation of early detection programs in Peru.

Humans↗

PubMed1991

Identification of common variant alleles of the human guanosine monophosphate reductase gene.

Examination of nucleotide sequences of genomic DNA samples obtained from several unrelated Caucasians and orientals revealed the existence of four variant alleles in the chromosome 6-linked quanosine monophosphate reductase locus. The wild-type gene has T at position 42 (counting from A of the chain initiation codon), C at 630, G at 700, and T at 766, i.e., its structure is T(42)-C(630)-G(700)-T(766). The variant gene, T-T-G-T, was found in about 10% of the loci examined. The C-to-T change at 630 was silent and did not induce any amino acid substitution (His at amino acid residue 210), but it created an additional NcoI cleavage site in the variant gene. The frequency of another variant, the T-C-G-A gene, was about 30%. The T-to-A change at 766 caused an amino acid substitution Phe----Ile at amino acid residue 256 in the variant protein. Frequencies of the C-C-G-T variant and the T-C-A-T variant were probably lower than 5% in Caucasians and orientals.

Alleles↗

PubMed2025

Identification of pathogenic variants in six Chinese families with keratoconus of autosomal dominant inheritance: pathogenicity analysis and variable phenotype.

PURPOSE: Keratoconus (KC) is a bilateral, asymmetric disease causing corneal thinning, irregular astigmatism, and vision decline, with unclear etiology. This study aims to investigate pathogenic variants of candidate genes in Chinese KC families via whole exome sequencing (WES). METHODS: The Pentacam 3D anterior segment analysis system was applied for keratectasia detection, and the Corvis ST was used for corneal biomechanics measurement. Probands from KC families were screened via WES and further verified in other family members through Sanger sequencing. Additionally, qPCR was used to validate copy number variants and identify pathogenic gene loci. The identified variants were then classified according to the Standards and Guidelines for the Interpretation of Sequence Variants published by the American College of Medical Genetics and Genomics (ACMG). Finally, STRING protein-protein interaction (PPI) networks analysis was performed to investigate interactions among candidate gene-related proteins. RESULTS: Using WES, four heterozygous missense variants were detected in the ZNF469, KRT12, COL8A2, and COL18A1 genes: c.4384G > A: p.Asp1462Asn, c.1229T > G:p.Val410Gly, c.505A > G:p.Ile169Val, and c.1159G > A:p.Gly387Arg. Additionally, a heterozygous frameshift variant was detected in the PMS2 gene: c.1551_1572del:p.Ser517Argfs*71. The affected parents carried the same variants as the probands verified by Sanger sequencing. A copy number variant was detected in the DPP6 gene: seq[GRCh38] dup(7)(q36.2q36.2) chr7:g.153782360_ 153982491dup. According to ACMG guidelines, ZNF469, KRT12, COL8A2, and COL18A1 gene variants are Likely Pathogenic; PMS2 and DPP6 gene variants are Pathogenic. STRING analysis highlights a tightly interconnected network centered on COL8A2, involving COL18A1, FN1, ZNF469, and KRT12. DPP6 was involved in KC via affecting FN1. In four of six autosomal dominant KC (adKC) families, affected parents had the same variants as probands but milder phenotypes. CONCLUSION: In this study, six novel variants in ZNF469, KRT12, COL8A2, COL18A1, PMS2, and DPP6 were linked to adKC. Family phenotypes showed variable expressivity with irregular dominance inheritance. Abnormal KC-related gene protein expression may contribute to corneal structural instability. This study broadened KC genetic screening candidates and suggested genetic testing could aid early KC diagnosis and intervention.

Adult↗

PubMed1991

DNase activity in Costa Rican crotaline snake venoms: quantification of activity and identification of electrophoretic variants.

DNase activity of Costa Rican crotaline snake venoms from the genera Bothrops, Crotalus and Lachesis was quantified by an enzymodiffusion method on agarose/DNA gels containing ethidium bromide. The reaction is detected as a ring lacking fluorescence when gels are visualized under u.v. light. Electrophoresis of non-fluorescent areas demonstrated DNA degradation. All of the venoms had DNase activity, B. schlegelii being most active. Venoms from B. schlegelii and B. asper induced an inner hyper-fluorescent ring in addition to the external non-fluorescent ring, probably caused by the formation of complexes between DNA and highly basic proteins present in these venoms. In order to study the number of electrophoretic DNase variants, venoms were separated by analytical isoelectric focusing on polyacrylamide minigels, proteins were transferred to nitrocellulose paper and the paper was placed over an agarose gel containing DNA. Then the agarose gel was stained with ethidium bromide and the bands of DNase activity were visualized under u.v. light. All the venoms tested, as well as commercial DNase showed several bands with DNase activity. The majority of venom DNase variants have basic pIs although bands with acidic pIs were also present in B. godmani and L. muta venoms. No major differences in the DNase electrophoretic pattern were observed between individual venoms of adult B. asper specimens nor between lyophilized and frozen venoms.

Crotalid Venoms↗

PubMed1977

Restoration of hemoglobin function in stored EDTA blood. Application in identification of hemoglobin variants with abnormal oxygen affinity.

The incubation of stored blood in a mixture of inosine, pyruvate, glucose, and phosphate restores the O2 affinity of hemoglobin to physiologic levels, as measured by the configuration of the dissociation curve and the P50. This regeneration of normal hemoglobin function not only is consistent for samples anticoagulated with EDTA and stored eight days at 4 C but also is demonstrable for at least 19 days of 4 C storage of EDTA-anticoagulated whole blood. This regeneration procedure is simple to perform and makes it possible to measure reliably O2 affinity in blood samples transmitted by mail.

Blood Preservation↗

PubMed1992

Genotyping of Chlamydia trachomatis from a trachoma-endemic village in the Gambia by a nested polymerase chain reaction: identification of strain variants.

Direct amplification of the major outer membrane protein (MOMP) gene by polymerase chain reaction (PCR) was used to identify Chlamydia trachomatis in eye swabs from clinically active cases of endemic trachoma in a Gambian village. Chlamydial DNA was detected in 51% of 96 subjects with clinically active disease and in 5% of 37 clinically negative individuals. The PCR detection was combined with typing, using nested primers to variable sequences (VS) 1, 2, and 4 of the MOMP genes to distinguish between trachoma genotypes A, B, and C, respectively. Genotypes A and B were detected in the village, with some individuals harboring both genotypes within the same eye. DNA sequencing revealed strain variants of both genotypes. Typing of genotype and strain variants is now in progress to study trachoma transmission within the village.

Bacterial Outer Membrane Proteins↗

PubMed1991

Isolation and identification of a variant of bluetongue virus serotype 11 from a ram in a bluetongue outbreak in western Texas.

A field strain of bluetongue virus was isolated from a blood sample of a ram during an outbreak of bluetongue in November 1985 in western Texas. In this bluetongue outbreak at least 25 of the 2,000 sheep were infected. Isolation was made by intravenous inoculation of 11-day-old embryonated chicken eggs. The serotype was identified as serotype 11 by serum neutralization tests. The genomic pattern on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) of the new isolate is similar to that of bluetongue virus prototype 11. Comparisons were also made with proteins labeled in vivo with [3H]leucine and separated by SDS-PAGE. We conclude that this virus belongs to serotype 11, with slight differences in both genome and protein electrophoretic patterns.

Animals↗

PubMed1990

Identification of two variant short chain acyl-coenzyme A dehydrogenase alleles, each containing a different point mutation in a patient with short chain acyl-coenzyme A dehydrogenase deficiency.

Two distinct mutant alleles of the precursor (p) short chain acyl-CoA dehydrogenase (SCAD) gene were identified in a SCAD-deficient patient (YH2065) using the polymerase chain reaction to amplify cDNA synthesized from total RNA from her fibroblasts. Cells from this patient had previously been shown to synthesize a labile variant SCAD in contrast to the normal stability of variant SCADs in two other SCAD-deficient cell lines (Naito, E., Y. Indo, and K. Tanaka. 1989. J. Clin. Invest. 84:1671-1674). In the present study, both mutant alleles of YH2065 were found to contain a C----T transition, one at position 136 and the other at position 319 of the coding region of pSCAD cDNA. Clones of cDNA amplified from this region showed only one of the C----T transitions, indicating that each mutation was derived from different pSCAD alleles. Each of these mutations altered a known restriction endonuclease site, and restriction analysis of additional cDNA clones from amplified mutant cDNA and Southern blotting of mutant genomic DNA confirmed the presence of two unique mutant alleles in YH2065, indicating YH2065 is a compound heterozygote. These C----T transitions result in the substitution of Arg-22 and Arg-83 of the mature SCAD with Trp and Cys, respectively.

Acyl-CoA Dehydrogenases↗