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Results for “Genomic diagnostics”

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PubMed1995

A non-radioactive DNA diagnostic procedure for the detection of malarial infection: general application to genome with repetitive sequences.

A novel non-radioactive DNA diagnostic method has been developed to detect Plasmodium falciparum infection in whole blood. In this method a drop of blood from a finger prick is added to a lysing solution containing a biotinylated oligonucleotide whose sequence design is based on the repeated sequence of the parasite genome. The mixture is heated in a boiling water bath and then added to a microtitre plate where the 'target-bioprobe hybrids' are captured by the immobilized oligonucleotides. The plate is then washed to remove the coloured material and the biotinylated oligonucleotide retained on the plate is assayed by streptavidin-alkaline phosphatase conjugate. This method has also been tested in field trials by double-blind studies to detect P.falciparum infection in blood samples. Results indicate that this method is superior to the classical blood smear examination for its speed and its ease in large epidemiological surveys and is especially useful in identifying clinical malaria in endemic areas where the semi-immune population predominates. The method described can be of general application for the detection of any foreign pathogen in blood, other body fluids and tissue samples, provided the DNA probe employed constitutes a part of the repeated sequence of the genome and is unique.

Animals↗
PubMed2000

[Hereditary hearing loss: new diagnostic possibilities].

Mutations in many different genes can result in hearing loss. Using different molecular genetic methods, the disease-causing gene mutations can often be identified or at least localised to defined regions of the genome. These new diagnostic possibilities result from the localisation and identification of a number of hearing-loss genes in the last five years. Diagnostic investigations should always be accompanied by a genetic counselling of the family. In addition, the isolation thus far of 11 genes mutated in autosomal dominant inherited hearing loss, as well as of 6 genes mutated in autosomal recessive inherited hearing loss, has contributed to a better understanding of the molecular pathology of hearing loss in general. However, we are only beginning to see the whole picture, as an estimated 50 to 80 hearing loss genes remain to be discovered.

Chromosome Mapping↗
PubMed2003

Value of comparative genomic hybridization and fluorescence in situ hybridization for molecular diagnostics in multiple myeloma.

Chromosomal abnormalities, such as 13q deletions, are emerging as important prognostic factors in multiple myeloma. Fluorescence in situ hybridization (FISH) using specific DNA probes is the technique most widely used for the determination of genomic aberrations in this disease. The utility of comparative genomic hybridization (CGH) for molecular diagnostics in plasma cell malignancies has not been systematically analysed. We investigated tumour samples of patients with multiple myeloma (n = 43) or plasma cell leukaemia (n = 3) using CGH and FISH with five DNA probes localized to chromosome bands 1p22, 6q21, 11q22-q23, 13q14 and 17p13. By CGH, the most frequent genomic changes were gains on chromosomes 1q, 9q and 11q, as well as losses on chromosomes 13q, 6q, Xp and Xq. By FISH, trisomy 11q was identified at a similar frequency to the 13q deletion (42%). Compared with FISH data, the sensitivity of CGH was 80.7% and the specificity was 97.5%. Thirty-two aberrations found by FISH were not identified by CGH, mostly as a result of the proportion of cells carrying the respective aberrations, or because of the limited spatial resolution of CGH. Our data indicate that, for clinical molecular diagnostics in multiple myeloma, FISH with a disease-specific DNA probe set is superior to CGH analysis.

Adult↗
PubMed1996

Genomic distribution of 5' TTCCA 3' repeat motif and its diagnostic potential in human Y-chromosome-related anomalies.

We have studied genomic distribution of a simple repeat motif 5' TTCCA 3' derived from the DYZ1 fraction of the human Y chromosome employing restriction fragment length polymorphism and in situ hybridization techniques. This has led us to develop a synthetic DNA based genetic marker specific to human genome. Randomly selected human genomic DNA from both sexes, digested with a total of 16 restriction enzymes, OAT20Y probe comprising four repeat units of 5'TTCCA 3' motif failed to reveal fragment length polymorphisms. In contrast, with most of the enzymes, several multilocus monomorphic bands and with a few enzymes, smeary signals were detected. In situ hybridization of the OAT20Y probe with human chromosomes revealed grains on the long arm of the Y chromosome, whereas the X-chromosome and autosomes showed random distribution of the grains without any preferential labeling in the centromeric or telomeric regions. The OAT20Y probe uncovers a 3.4 kb isomorphic band exclusively in the human male DNA digested with Hae III enzyme. Using the OAT20Y probe, we have detected the presence of Y chromosome in mosaic cell populations of Turner's patients with dysgenetic gonads and high levels of LS/FSH. The presence of Y chromosome in these patients has been associated with an increased risk of gonadoblastoma. The OAT20Y probe offers sensitivity and accuracy for the detection of Y-chromosome-bearing cells in a mosaic cell population and, consequently, help in better management of the patients.

Blotting, Southern↗
PubMed2006

Rapid DNA mapping by fluorescent single molecule detection.

DNA mapping is an important analytical tool in genomic sequencing, medical diagnostics and pathogen identification. Here we report an optical DNA mapping strategy based on direct imaging of individual DNA molecules and localization of multiple sequence motifs on the molecules. Individual genomic DNA molecules were labeled with fluorescent dyes at specific sequence motifs by the action of nicking endonuclease followed by the incorporation of dye terminators with DNA polymerase. The labeled DNA molecules were then stretched into linear form on a modified glass surface and imaged using total internal reflection fluorescence (TIRF) microscopy. By determining the positions of the fluorescent labels with respect to the DNA backbone, the distribution of the sequence motif recognized by the nicking endonuclease can be established with good accuracy, in a manner similar to reading a barcode. With this approach, we constructed a specific sequence motif map of lambda-DNA. We further demonstrated the capability of this approach to rapidly type a human adenovirus and several strains of human rhinovirus.

Adenoviruses, Human↗
PubMed2000

What we can learn from the Mycobacterium tuberculosis genome sequencing projects.

A major milestone in tuberculosis research occurred in June 1998 with the report of the genomic sequence of Mycobacterium tuberculosis H37Rv. The complete determination of the 4411529 base pairs of the M. tuberculosis genome opens avenues for new scientific opportunities in basic science and clinical research on tuberculosis. In this paper we will review the findings presented by the complete genome and discuss the impact that this sequence will have on the areas of comparative genomics, bacterial pathogenesis, and diagnostics development for tuberculosis. Indirect benefits of the complete genome sequence are anticipated in the areas of drug development and vaccine development as future discoveries in bacterial pathogenesis and immunology accrue.

DNA, Bacterial↗
PubMed2026

Availability and public reimbursement of early breast cancer care across European expert centres: a PORTRAIT from an EUSOMA initiative.

BACKGROUND: Cross-country disparities in access to guideline-recommended early breast cancer care persist across Europe. PORTRAIT is a clinician-reported, cross-sectional access study mapping availability and state reimbursement of key services across the early breast cancer pathway. METHODS: A 49-item survey covering diagnostics, pathology and genomics, systemic therapy, surgery, radiotherapy, and supportive care was emailed from June to September 2024 to multidisciplinary teams at one expert breast centre in 42 European countries. Respondents provided a consensus perspective on service availability and reimbursement. Descriptive proportions with full, partial, or no access were calculated. RESULTS: Thirty-nine countries responded (93%). Core diagnostics were widely available, but gaps persisted: MRI-guided biopsy was absent in 29% of countries and vacuum-assisted biopsy was fully reimbursed in 66%. Genomic assays were unavailable in 14% and not fully reimbursed in 35%. Public funding gaps were reported for PARP inhibitors (33%) and CDK4/6 inhibitors (26%). Immediate implant-based reconstruction and biological meshes lacked reimbursement in 21% and 33%, respectively. Despite broad availability of hypofractionated radiotherapy, 38% of countries still used per-fraction reimbursement. Psycho-oncology was limited in 35%, fertility preservation in 46%, and patient-reported outcome measures absent in 43%. CONCLUSION: Basic services are nearly universal, but gaps persist in advanced imaging, molecular testing, targeted therapies, radiotherapy reimbursement, reconstructive/oncoplastic surgery, and survivorship care. PORTRAIT identifies practical targets for policy audit, reimbursement alignment, and resource stewardship. Findings reflect clinician perspectives from expert centres, potentially representing best specialist care rather than average national care, and are not population-representative estimates or direct measures of patient outcomes.

Humans↗
PubMed2006

Genomics of hepatitis B and C infections: diagnostic and therapeutic applications of microarray profiling.

Microarray profiling offers many potential advances in diagnostic and therapeutic intervention in human disease because of its unparalleled ability to conduct high-throughput analysis of gene expression. However, limitations of this technique relate in part to issues regarding the various methodologies and experimental designs as well as difficulties in the interpretation of results. Despite this, microarray profiling has led to a better understanding of the molecular pathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Key events in clearance and the development of chronicity of HCV have been identified that may prove to have a role in the development of future treatments. In addition, pharmacogenomic studies of interferon-based treatment for chronic HCV and HBV have provided mechanistic insights into the therapeutic action of interferons. These advances have implications with respect to the development of improved therapeutic agents. New biomarkers for cancer screening and gene profiles with prognostic value for survival have also been developed for hepatocellular carcinoma, which frequently complicates chronic viral hepatitis. Thus, microarray profiling offers enormous potential for improvements in antiviral therapy and our understanding of blood-borne viral hepatitis.

Animals↗
PubMed2002

Identification of novel Mycobacterium tuberculosis antigens with potential as diagnostic reagents or subunit vaccine candidates by comparative genomics.

An independent review for the British government has concluded that the development of a cattle vaccine against Mycobacterium bovis holds the best long-term prospects for tuberculosis control in British herds. The development of complementary diagnostic tests to differentiate between vaccinated and infected animals is necessary to allow the continuation of test-and-slaughter-based control policies alongside vaccination. Vaccination with M. bovis bacillus Calmette-Guérin (BCG), the only available vaccine, results in tuberculin purified protein derivative sensitivity and has shown varying vaccine efficacies in cattle. Thus, identification of more-specific reagents to distinguish between vaccination and infection, as well as the identification of subunit vaccine candidates for improved tuberculosis vaccines, is a research priority. In the present study, we applied comparative genomics to identify M. bovis-Mycobacterium tuberculosis antigens whose genes had been deleted in BCG Pasteur. In total, 13 open reading frames (ORFs) from the RD1, RD2, and RD14 regions of the M. tuberculosis genome were selected. Pools of overlapping peptides spanning these ORFs were tested in M. bovis-infected (n = 22), BCG-vaccinated (n = 6), and unvaccinated (n = 10) control cattle. All were recognized in infected cattle, with responder frequencies varying between 16 and 86%. In particular, eight highly immunogenic antigens were identified whose potentials as diagnostic reagents or as subunit vaccines warrant further study (Rv1983, Rv1986, Rv3872, Rv3873, Rv3878, Rv3879c, Rv1979c, and Rv1769).

Amino Acid Sequence↗
PubMed2004

Sequencing needs for viral diagnostics.

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (near neighbors) that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near-neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near-neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. Severe acute respiratory syndrome and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near-neighbor sequences are urgently needed. Our results also indicate that double-stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

Base Sequence↗
PubMed2003

New approaches for biomarker discovery in lung cancer.

Lung cancer remains the most common cause of cancer death in the US and worldwide. Currently, there is no implemented population-based screening for lung cancer. Of all the markers identified, none have achieved sufficient diagnostic significance to reach clinical application. Here we discuss the status of lung cancer early diagnostics, and the genomic and proteomic approaches currently undertaken for biomarker discovery. We then introduce the ANTIBIOMIX approach that enables high-throughput target discovery by interrogating biological samples using a collection of thousands of polyclonal antibodies. The development of specific and sensitive diagnostic assays using patient's biological fluids, such as sputum and serum, will improve screening, monitoring of disease progression and treatment response, and surveillance for recurrence.

Biomarkers, Tumor↗
PubMed2006

[Diagnostic performance of specific IgM detection and genomic amplification in rubella].

Nowadays, most exanthematic diseases for which a vaccine is available affect young adults. A large percentage of these cases prove to be rubella. The aim of this study is to assess the performance of specific IgM and RT-PCR for the diagnosis of rubella infection. Fifty-nine patients with clinically suspected measles or rubella, and with available serum, whole blood, urine and pharyngeal exudate specimens were studied. RT-PCR in pharyngeal exudate was found to be the most effective marker at the start of the disease (mean, 2.5 days). IgM detection yielded a larger percentage of positive results (76.2%), but at a later time (3.7 days).

Adolescent↗
PubMed2025

Future-proofing tuberculosis therapy: framework for concurrent drug and resistance testing development.

The rapid emergence of resistance to novel tuberculosis drugs, such as bedaquiline, is a key threat to the long-term effectiveness of novel regimens. Given that the introduction of these agents has enabled the introduction of an all-oral regimen for rifampicin-resistant and multidrug-resistant tuberculosis, the rise of resistance underscores the urgent need to safeguard their efficacy and responsible use. A major barrier is the delay in developing reliable tools to detect resistance to novel compounds, which limits clinical decision-making and surveillance efforts. Herein, we outline a framework for integrating the development of drug susceptibility testing alongside tuberculosis drug development, including early stage resistance profiling and defining appropriate epidemiological cutoff values. We highlight key gaps, including the need for structured partnerships between drug developers, diagnostic manufacturers, regulators, research institutions, funders, and policy makers. We propose a roadmap to accelerate drug susceptibility testing and development of new tuberculosis regimens, ensuring that resistance detection maintains pace with the introduction of novel drugs. Establishing collaborative platforms for data sharing, genomic analysis, and diagnostic innovation will help ensure that resistance detection evolves in step with drug development, thereby preserving novel treatments and improving global tuberculosis care.

Humans↗
PubMed2003

Genomic approach to identification of Mycobacterium bovis diagnostic antigens in cattle.

Differential delayed-type hypersensitivity skin testing with tuberculin purified protein derivatives from Mycobacterium bovis and M. avium is the standard for diagnosing bovine tuberculosis. However, improved tests based on defined, specific antigens are urgently needed. In the present study, a combination of bioinformatics, molecular biology, and bovine models of infection were used to screen mycobacterial proteins for their potential as diagnostic reagents which could be used in a whole-blood assay for diagnosis of tuberculosis. Initial screening of 28 proteins selected in silico and expressed as recombinants in Escherichia coli indicated that CFP-10, ESAT-6, TB27.4, TB16.2, TB15.8, and TB10.4 induced strong gamma interferon responses in experimentally infected cattle. A more thorough investigation over time in two groups of animals infected with a high (10(6) CFU) and a low (10(4) CFU) dose of M. bovis revealed that, for both groups, the strength of the in vitro response to individual antigens varied greatly over time. However, combining the results for ESAT-6, CFP-10, and TB27.4, possibly supplemented with TB10.4, gave sensitivities at different infection stages close to those obtained with M. bovis purified protein derivative. Importantly, while responsiveness to ESAT-6 and CFP-10 correlated strongly for individual samples, the same was not the case for ESAT-6 and TB27.4 responsiveness. The results suggest that combinations of specific antigens such as these have great potential in development of optimized diagnostic systems for bovine tuberculosis.

Animals↗
PubMed2004

A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs.

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor (VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.

Amino Acid Sequence↗
PubMedDate not supplied

[A comparative study of the diagnostic value of peptides, corresponding to various genomic sequences of the hepatitis delta virus].

A set of 5 peptides from the immunodominant region (65-80 aa) of delta-antigen was prepared by solid phase synthesis. Peptide 71-80 was synthesized in two variants with different amino acid residues in positions 73, 74, 76. Free peptides and their conjugates with bovine serum albumin were tested for antigenicity in ELISA. Correlation between the length of the peptide chain and its antigenic activity was noted. Peptides 65-80 and 69-80 demonstrated positive reaction with all sera from acute HDV patients. Both variants of peptide 71-80 reacted with 83% of positive sera. The smaller peptide 73-80 reacted strongly with one positive serum out of five used.

Amino Acid Sequence↗