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PubMed2004

A form of albinism in cattle is caused by a tyrosinase frameshift mutation.

We used PCR amplification of cDNA prepared from skin biopsies to determine the full-length protein-coding sequence of tyrosinase ( TYR) in cattle of several coat colors. An insertion of a cytosine was detected in an albino Braunvieh calf, which resulted in a frameshift which caused a premature stop codon at residue 316. This insertion was found in the homozygous state in this calf and the genomic DNA of two related albino calves. All six parents of these calves were heterozygous for this insertion. However, an albino Holstein calf did not have this insertion, nor was any other mutation detected in the partial TYR sequence obtained from the genomic DNA available. Diagnostic genotyping tests were developed to detect this mutation in Braunvieh cattle.

Albinism↗

PubMed2004

Severe acute respiratory syndrome (SARS)--paradigm of an emerging viral infection.

An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch's postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent's environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more "traditional" techniques carried out to an excellent standard.

Antiviral Agents↗

PubMed2002

Protein microarray technology.

Microarray technology allows the simultaneous analysis of thousands of parameters within a single experiment. Microspots of capture molecules are immobilized in rows and columns onto a solid support and exposed to samples containing the corresponding binding molecules. Readout systems based on fluorescence, chemiluminescence, mass spectrometry, radioactivity or electrochemistry can be used to detect complex formation within each microspot. Such miniaturized and parallelized binding assays can be highly sensitive, and the extraordinary power of the method is exemplified by array-based gene expression analysis. In these systems, arrays containing immobilized DNA probes are exposed to complementary targets and the degree of hybridization is measured. Recent developments in the field of protein microarrays show applications for enzyme-substrate, DNA-protein and different types of protein-protein interactions. Here, we discuss theoretical advantages and limitations of any miniaturized capture-molecule-ligand assay system and discusses how the use of protein microarrays will change diagnostic methods and genome and proteome research.

Gene Expression↗

PubMed2002

Protein microarray technology.

Microarray technology allows the simultaneous analysis of thousands of parameters within a single experiment. Microspots of capture molecules are immobilised in rows and columns onto a solid support and exposed to samples containing the corresponding binding molecules. Readout systems based on fluorescence, chemiluminescence, mass spectrometry, radioactivity or electrochemistry can be used to detect complex formation within each microspot. Such miniaturised and parallelised binding assays can be highly sensitive, and the extraordinary power of the method is exemplified by array-based gene expression analysis. In these systems, arrays containing immobilised DNA probes are exposed to complementary targets and the degree of hybridisation is measured. Recent developments in the field of protein microarrays show applications for enzyme-substrate, DNA-protein and different types of protein-protein interactions. This article discusses theoretical advantages and limitations of any miniaturised capture-molecule-ligand assay system and discusses how the use of protein microarrays will change diagnostic methods and genome and proteome research.

Biotechnology↗

PubMed2001

Genotyping of two mutations in the HFE gene using single-base extension and high-performance liquid chromatography.

Currently, a major focus of human genetics is the utilization of single-nucleotide polymorphisms for clinical diagnostics, whole-genome linkage disequilibrium screens to identify common disease genes such as Alzheimer disease, determination of the recent evolutionary history of a species, and the process of speciation. We have examined single-nucleotide extension coupled with high-performance liquid chromatography as a method to simultaneously genotype two SNPs occurring in the coding region of the HFE gene that produce clinical effects. This assay allows concurrent genotyping of the C282Y and H63D mutations in 11 min and is 100% concordant with current testing methods for both of these mutations.

Base Sequence↗

PubMed2005

Double-wavelength technique for surface plasmon resonance measurements: basic concept and applications for single sensors and two-dimensional sensor arrays.

A new technique for on-line monitoring of analyte binding to sensor surfaces by surface plasmon resonance (SPR) detection is described. It is based on differential measurements using two wavelengths provided by two diode lasers. The technique is as simple and robust as the conventional SPR detection measuring the reflected radiation at fixed incidence angle, but it has the advantage of being nonsensitive to variations of the resonance width and providing essentially higher signal/noise ratios. The paper presents the first four channel prototype system for parallel 2D-monitoring at four different spots. One channel is always used as a reference to compensate temperature fluctuations and nonspecific adsorptions. Calibration with sucrose solutions revealed an absolute sensitivity of Deltan approximately 5 x 10(-6). The new technique is tested with a biotin-streptavidin binding and with hybridization/denaturation of DNA. Biotin binding to a streptavidin monolayer is detected with a signal/noise ratio of about 5, which demonstrates the high potential of the new technique for applications in drug discovery. Applications to gene analysis are tested with short oligonucleotides of the sequences used for genotyping human hepatitis C viruses. A selective response to complementary oligonucleotides is observed. The high reproducibility in subsequent cycles of hybridization/denaturation (by formamide or by heating) points out potential applications of the technique in medical diagnostics, food industry, genomics, and proteomics too.

Biosensing Techniques↗

PubMed2026

DNA-guided CRISPR-Cas12 for cellular RNA targeting.

Here, we present ΨDNA, a DNA-based guide that enables RNA targeting by Cas12 nucleases, overcoming the traditional reliance on RNA-guided systems. We engineer ΨDNA to mimic a CRISPR RNA (crRNA) scaffold in reverse orientation, allowing AsCas12a and Cas12i1 to recognize RNA and trigger strong single-stranded DNA trans-cleavage for sensitive detection of diverse RNA species, including 100% accurate hepatitis C virus RNA detection in clinical samples. ΨDNA also achieves 70-95% multiplex knockdown of endogenous intracellular RNA transcripts through ribosome stalling across multiple human cell lines. Mechanistic studies reveal that activity depends on a stem loop that stabilizes a catalytically competent Cas12-ΨDNA-RNA complex. Lastly, codelivery of crRNA and ΨDNA enables simultaneous DNA editing and RNA knockdown with a single effector and modular fusions of different enzymes to AsCas12a extend ΨDNA to RNase H-mediated RNA degradation and METTL3-based epitranscriptomic editing. Together, ΨDNA guides constitute an adaptable toolkit that extends Cas12 systems beyond genome editing and diagnostics to enable precise, programmable control of cellular transcriptomes and their epitranscriptomic marks.

Journal Article↗

PubMed2000

Natural selection mapping of the warfarin-resistance gene.

In theory, genes under natural selection can be revealed by unique patterns of linkage disequilibrium (LD) and polymorphism at physically linked loci. However, given the effects of recombination and mutation, the physical extent and persistence of LD patterns in natural populations is uncertain. To assess the LD signature of selection, we survey variation in 26 microsatellite loci spanning an approximately 32-cM region that includes the warfarin-resistance gene (Rw) in five wild rat populations having resistance levels between 0 and 95%. We find a high frequency of heterozygote deficiency at microsatellite loci in resistant populations, and a negative association between gene diversity (H) and resistance. Contrary to previous studies, these data suggest that directional rather than overdominant selection may predominate during periods of intense anticoagulant treatment. In highly resistant populations, extensive LD was observed over a chromosome segment spanning approximately 14% of rat chromosome 1. In contrast, LD in a moderately resistant population was more localized and, in conjunction with likelihood ratios, allowed assignment of Rw to a 2. 2-cM interval. Within this genomic window, a diagnostic marker, D1Rat219, assigned 91% of rats to the correct resistance category. These results further demonstrate that "natural selection mapping" in field populations can detect and map major fitness-related genes, and question overdominance as the predominant mode of selection in anticoagulant-resistant rat populations.

Animals↗

PubMed2026

Molecular Pathogenesis, Global Epidemiological Trends, and Treatment Strategies for Pteropine Orthoreoviruses: A Narrative Review.

Pteropine orthoreoviruses are emerging bat-borne zoonotic viruses of the genus Orthoreovirus (family Reoviridae), increasingly recognized as causes of acute respiratory disease in humans. Originally grouped with the largely non-pathogenic mammalian orthoreoviruses, they have challenged that view through their association with severe influenza-like illness, evidence of human-to-human transmission, and a broad geographic range across the Old World. Maintained primarily in fruit bats of the family Pteropodidae, they are now linked to neurological as well as respiratory disease. This narrative review synthesizes current knowledge of their molecular pathogenesis, zoonotic ecology, and global epidemiology, integrating recent advances in phylogeography, reassortment-driven evolution, spillover dynamics, and translational biomedical applications within a unified One Health framework. Genomic diversity, reassortment potential, and the unique fusion-associated small transmembrane proteins together underpin viral adaptability and pathogenicity. Major gaps nonetheless remain in transmission dynamics, host adaptation, shedding ecology, and pandemic potential. Future priorities should include integrated genomic surveillance, improved diagnostic strategies, validated experimental models, and interdisciplinary One Health approaches to strengthen outbreak preparedness and prevention.

Bat-borne viruses↗

PubMed2000

Amplifiable DNA from gram-negative and gram-positive bacteria by a low strength pulsed electric field method.

An efficient electric field-based procedure for cell disruption and DNA isolation is described. Isoosmotic suspensions of Gram-negative and Gram-positive bacteria were treated with pulsed electric fields of <60 V/cm. Pulses had an exponential decay waveform with a time constant of 3.4 micros. DNA yield was linearly dependent on time or pulse number, with several thousand pulses needed. Electrochemical side-effects and electrophoresis were minimal. The lysates contained non-fragmented DNA which was readily amplifiable by PCR. As the method was not limited to samples of high specific resistance, it should be applicable to physiological fluids and be useful for genomic and DNA diagnostic applications.

Cell Fractionation↗

PubMed2026

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N≈1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age↗

PubMed2026

Microbe Profile: Candidozyma auris: an emergent and resilient yeast and new antifungal strategies.

Candidozyma auris is an emerging opportunistic yeast that is important because of its multidrug resistance, persistence in healthcare environments and ability to cause outbreaks. Since its discovery in 2009 in Japan, it has rapidly spread worldwide and is now recognized as a major global public health threat and was recognized by the World Health Organization (WHO) in 2022 as a critical priority fungal pathogen. Distinct phylogeographic clades demonstrate simultaneous emergence on different continents, suggesting ecological or environmental triggers. Clinical management is complicated by frequent resistance to fluconazole, reduced susceptibility to amphotericin B and echinocandins, and frequent misidentification by traditional laboratory methods. Continued genomic surveillance, improved diagnostics and new antifungal strategies are urgently needed, supported by enhanced infection prevention and control procedures.

Antifungal Agents↗

PubMed2003

Autonomous system for Web-based microarray image analysis.

Software-based feature extraction from DNA microarray images still requires human intervention on various levels. Manual adjustment of grid and metagrid parameters, precise alignment of superimposed grid templates and gene spots, or simply identification of large-scale artifacts have to be performed beforehand to reliably analyze DNA signals and correctly quantify their expression values. Ideally, a Web-based system with input solely confined to a single microarray image and a data table as output containing measurements for all gene spots would directly transform raw image data into abstracted gene expression tables. Sophisticated algorithms with advanced procedures for iterative correction function can overcome imminent challenges in image processing. Herein is introduced an integrated software system with a Java-based interface on the client side that allows for decentralized access and furthermore enables the scientist to instantly employ the most updated software version at any given time. This software tool is extended from PixClust as used in Extractiff incorporated with Java Web Start deployment technology. Ultimately, this setup is destined for high-throughput pipelines in genome-wide medical diagnostics labs or microarray core facilities aimed at providing fully automated service to its users.

Algorithms↗

PubMed1998

Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population.

INTRODUCTION: The regulatory role of apolipoprotein E in lipid transport and metabolism was utilized to investigate the allelic association between the apolipoprotein E4 (apoE4) allele and vascular dementia (VD) in a selected sample of Hungarian patients with multiple deep subcortical infarcts and leukoaraiosis. MATERIAL AND METHODS: Thirty-four Caucasian VD cases and 79 healthy control probands were involved in this study according to the criteria of ICD-10 and NINDS-AIREN International Workshop Diagnostic Criteria. The genomic DNA was isolated from whole blood and the apoE alleles were determined by polymerase chain reaction. RESULTS: The E2, E3 and E4 allele frequencies in the VD group were 5%, 76%, and 19%, respectively; and significant (P<0.03) differences were found in comparison with the data on the healthy controls (E2, 6%; E3, 87%; E4, 8%). The apoE4 allele frequency was intermediate between HC and Alzheimer's dementia group (28%). CONCLUSION: These results indicate that the apoE4 allele could be a risk factor not only for certain primary degenerative, but also for vascular dementias.

Aged↗

PubMed2002

In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia.

Recent reports have established the prenatal origin of leukemia translocations and resultant fusion genes in some patients, including MLL-AF4 translocations in infants and TEL-AML1 translocations in children. We now report evidence for the prenatal origin of a translocation in childhood acute myeloid leukemia (AML). The t(8;21) AML1-ETO translocations were sequenced at the genomic level in 10 diagnostic leukemia samples from children with available neonatal Guthrie blood spots. Clonotypic genomic AML1-ETO sequences were detected in the Guthrie spots for 5 individuals, providing unambiguous evidence of prenatal origin in these cases. Two of these patients were older than 10 years of age at diagnosis, indicative of a protracted postnatal latency. Three of the patients were assessed for the persistence of genomic fusion sequences in complete clinical remission samples and were found to be positive. These data indicate that t(8;21) in childhood AML can arise in utero, possibly as an initiating event in childhood AML, and may establish a long-lived or stable parental clone that requires additional secondary genetic alterations to cause leukemia.

Acute Disease↗

PubMed2003

Dopamine transporter genotype influences the attention deficit in Korean boys with ADHD.

Attention appears to be inheritable, stable and influenced by genetic factors. The use of the Continuous Performance Test (CPT), as an endophenotypic measure, is valuable for genetic studies because it may show increased sensitivity to specific dimensions in attention deficit hyperactivity disorder. However, few studies have been designed to examine the influence of the genotype on attention level measured by CPT in ADHD patients. This study examinee the difference between 10/10 and 10/* genotype in the attention deficits measured by the CPT in ADHD patients. Forty-four unrelated ADHD patients were recruited from the psychiatric outpatients' clinic at Kangbuk Samsung Hospital. Two child psychiatrists made the diagnoses of ADHD using the DSM- IV diagnostic criteria. The genomic DNA was extracted from the blood, and analyzed to determine the genotype. A 40- base pair variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region was amplified. The attention deficits were measured by the test of variables of attention (T.O.V.A.). Between the 10/10 genotype and 10/* genotype, standard scores of the T.O.V.A were compared using a Mann-Whiney test. A comparison with the 10/10 genotype and 10/* genotype showed that those patients with the 10/10 genotype made less omission errors in the first quarter of the test (p < 0.05, by Mann-Whiney test). No significant differences were observed in the errors of commission, response time, variability. This study found that the 10/10 genotype made less omission errors on the T.O.V.A. This suggests that the dopamine transporter genotype influences the attention deficits measured by T.O.V.A.

3' Untranslated Regions↗

PubMed2026

Carbapenem-resistant Gram-negative pathogens: molecular epidemiology, diagnostic advances, and emerging therapeutic strategies.

Carbapenem-resistant Gram-negative pathogens (CR-GNPs) have become an important global health problem, contributing significantly to healthcare-associated infections, extended hospital stays, high mortality rates, and higher healthcare costs. The dissemination of carbapenem resistance is mainly attributed to the spread of carbapenemase-encoding genes, such as the Klebsiella pneumoniae carbapenemase (KPC), the New Delhi metallo-β-lactamase (NDM), the Verona integron-encoded metallo-β-lactamase (VIM), the imipenemase (IMP), and the oxacillinase-48 (OXA-48)-like enzymes associated with clinically important Gram-negative pathogens, including Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. As well as carbapenemase production, resistance can also develop via alteration of porins, upregulation of efflux pumps, and the buildup of several resistance factors, generating highly adaptable and hard-to-treat microbes. Phenotypic resistance patterns may not predict the underlying mechanism and accurate laboratory detection remains challenging. The identification and monitoring of carbapenem-resistant organisms have undergone improvement in recent years thanks to molecular diagnostics, rapid phenotypic tests, whole-genome sequencing and metagenomics. At the same time, new drugs have been developed, such as ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol and combinations of aztreonam, offering increased treatment options, but with emerging resistance an issue. This mini review covers the molecular epidemiology of CR-GNPs, the latest developments and challenges in diagnosing these infections, new therapeutic options, and future perspectives on genomic surveillance, antimicrobial stewardship, and precision medicine strategies to address the increasing threat of carbapenem resistance.

Gram-negative pathogens↗

PubMed2026

From Infection Control to Healthcare System Resilience: Lessons Learned from SARS-CoV-2 Research in Healthcare Workers.

The COVID-19 pandemic placed unprecedented pressure on healthcare systems and exposed healthcare workers (HCWs) to biological hazards, organizational pressures, and psychological strain. Evidence generated during the emergency shows that HCW protection cannot rely on isolated measures, but requires an integrated framework combining epidemiological surveillance, contact tracing, infection prevention and control, vaccination, occupational health, and workforce support. Contact tracing helped identify occupational exposures and clarify how duration, proximity, and inadequate use of personal protective equipment jointly shaped infection risk. Subsequent studies of reinfection showed that susceptibility reflected the interaction of viral circulation, individual immunity, and vaccination status. Vaccination reduced the clinical impact of SARS-CoV-2 and supported service continuity, although uptake depended on trust, communication, and management of adverse event concerns. The pandemic also highlighted substantial economic consequences and a high burden of psychological distress and burnout among HCWs. Building on this evidence, future preparedness should translate these lessons into permanent, adaptable infrastructure rather than temporary emergency arrangements, integrating interoperable, AI-assisted surveillance capable of combining occupational, diagnostic, vaccination, and genomic data to detect emerging risks early, while ensuring robust data governance and human oversight. Equally central is the need to address long-term workforce vulnerabilities, including Long COVID, attrition, and burnout, through early identification, rehabilitation, flexible return-to-work models, and sustained psychosocial support. Achieving this requires structured multidisciplinary collaboration among occupational medicine, infection control, epidemiology, mental health, and digital health specialists, moving from fragmented infection-control protocols to an integrated, proactive, and learning-oriented preparedness strategy. Protecting HCWs is therefore not only an occupational safety priority but a foundational prerequisite for safe, equitable, and sustainable healthcare delivery during future infectious threats.

Humans↗