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PubMed1994

Active and passive protection against variant and classic infectious bursal disease virus strains induced by baculovirus-expressed structural proteins.

Infectious bursal disease virus (IBDV) is responsible for a highly immunosuppressive disease in young chickens which causes significant economic losses to the poultry industry worldwide. The structural protein genes (VP2, VP3 and VP4) of a variant IBDV strain (GLS) were expressed in insect cells using a baculovirus expression system. Susceptible chickens vaccinated with a single dose of the recombinant IBDV antigens were completely protected against challenge with two variant strains of IBDV (GLS and Delaware), and partially protected against the standard challenge strain (STC). A booster dose of the recombinant antigens induced higher levels of neutralizing antibodies and afforded complete protection against both variant and standard virus challenges. Specific-pathogen-free hens vaccinated with a single dose of the same subunit vaccine produced virus-neutralizing antibodies that were capable of passively protecting the progeny from infection with variant IBDV.

Animals↗

PubMed1997

Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection.

Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, during and after seroconversion. These positively selected HIV-1 variants carried epitope sequence changes that either diminished or escaped CTL recognition. Other proviruses had mutations that abolished the Nef epitope altogether. These results provide clear evidence that CTLs exert selection pressure on the viral population in acute HIV-1 infection.

Adult↗

PubMed1999

Loss of pathogenic potential after cloning of the low-passage Borrelia burgdorferi ZS7 tick isolate: a cautionary note.

To study clonal polymorphism of Borrelia hurgdorferi antigens in the course of an experimental infection sequence, the low-passage tick isolate ZS7 was cloned by two rounds of agar subsurface plating. The resulting clones showed a variable pathogenic potential after experimental infection of C.B-17. scid mice. The test clone 4.2.II, selected for virulence by two passages in immunodeficient scid mice, failed to establish a successful infection in immunocompetent AKR/N mice, indicating the loss of pathogenicity traits required for evasion of the specific immune response. Cloning of natural or clinical B. burgdorferi isolates is a prerequisite for analyzing genetic and antigenic variation of the pathogen. However, the inevitable propagation in artificial media during cloning may lead to a loss of pathogenic features rendering the subsequent experimental infection of animals impossible. A combined procedure of in vitro cloning and in vivo selection also does not solve the dilemma because B. burgdorferi variants arise by recombinatorial processes in the pathogen's dynamic genome during the course of infection. Consequently, the resulting bacterial isolates from infected animal tissues represent again non-clonal, heterogeneous B. burgdorferi populations. In principle, cloning of a B. burgdorferi population is the appropriate method to analyze the polymorphism of individual molecules during infection. As a caveat, however, one has to envisage that during propagation of individual clones in vitro and in vivo independent genetic variations

Animals↗

PubMed2026

Automated patch clamp data improve variant classification and penetrance stratification for SCN5A-Brugada syndrome.

BACKGROUND AND AIMS: Brugada Syndrome (BrS) is an inherited arrhythmia disorder that causes an elevated risk of sudden cardiac death. Approximately 20% of patients with BrS have rare variants in SCN5A, which encodes the cardiac sodium channel NaV1.5. Genetic workup of BrS is often complicated by SCN5A variants of uncertain significance (VUS) and/or incomplete penetrance. This study deployed an SCN5A-BrS functional assay at cohort scale to facilitate the implementation of genetic and precision medicine. METHODS: All 252 missense and in-frame insertion/deletion SCN5A variants from a previously published large cohort of BrS cases (n = 3335 patients) were analysed using a calibrated high-throughput automated patch-clamp (APC) assay. Variant functional Z-scores were assigned evidence levels ranging from BS3_moderate (normal function) to PS3_strong (loss-of-function), as defined by American College of Medical Genetics and Genomics criteria. Functional evidence was combined with population frequency, hotspot, case counts, protein-length changes, and in silico predictions. Odds ratios of BrS case-control enrichment and penetrance for BrS were calculated from variant frequencies in the BrS cohort and in gnomAD. RESULTS: Most variants (146/252) were functionally abnormal (Z ≤ -2), with 100 having severe loss-of-function (Z ≤ -4). Functional evidence enabled the reclassification of 110 of 225 VUS; 104 to likely pathogenic and 6 to likely benign. SCN5A variants with loss-of-function were mainly localized to the transmembrane domains, especially the regions comprising the central pore. SCN5A variant penetrance was proportional to the severity of loss-of-function; variants with Z ≤ -6 had penetrance of 24.5% (15.9%-37.7% CI) and an odds ratio of 501 for BrS. CONCLUSIONS: This cohort-scale APC dataset stratifies SCN5A variants found in BrS patients into normal function 'bystander' variants that have a low risk of BrS and loss-of-function variants that have a high risk for BrS. Functional data can be integrated with other criteria to reclassify a substantial fraction of VUS. The dataset helps clarify the SCN5A-BrS relationship and will improve the diagnosis and clinical management of BrS probands and their families.

Humans↗

PubMed2001

Protection of neonatal macaques against experimental SHIV infection by human neutralizing monoclonal antibodies.

Neonatal macaques were completely protected against oral challenge with SHIV-vpu+, a simian-human immunodeficiency virus that encodes the envelope gene of a laboratory-adapted HIV strain, by pre- and post-natal treatment with a triple combination of human neutralizing monoclonal antibodies (mAbs). The mAbs were directed either against the CD4 binding site, a glycosylation-dependent gp120 epitope, or against a linear epitope on gp41. This triple combination was highly synergistic in vitro and neutralized primary HIV completely. Subsequently, oral challenge was performed with pathogenic SHIV89.6P, an animal-passaged variant of a chimeric virus that encodes the envelope gene of the primary, dual-tropic HIV89.6. Only post-natal treatment with a similar triple mAb combination was used. One out of 4 mAb-treated infants was completely protected from infection. In the other 3 treated animals, there was a tendency towards lower peak viral RNA loads compared with untreated controls. Two out of 4 mAb-treated infants maintained normal CD4+ T-cell numbers, in contrast to all controls that had steep declines at 2 weeks post-challenge. We conclude that the triple mAb combination significantly protected the neonates, even against mucosal challenge with pathogenic SHIV89.6P. Passively administered synergistic human mAbs may play a role in preventing mother-infant transmission of HIV, both against intrapartum transmission as well as against infection through breast milk. As passive immunization is a tool to assess correlates of immune protection, we conclude that the epitopes recognized by the mAbs in our combinations are important for AIDS vaccine development. Future passive immunization studies may reveal other important conserved epitopes.

AIDS Vaccines↗

PubMed1994

Signals and signs for lymphocyte responses.

The adaptive immune response protects us from infection in a world of pathogens that is forever evolving new variants. As the system is built on the generation of an open repertoire of receptors, the recognition of self is unavoidable, and is guarded against by deletion during lymphocyte development of those cells that are specific for ubiquitous self antigens, and the silencing of those that are specific for self antigens only encountered after cells achieve functional maturity in the periphery. This silencing occurs when lymphocytes recognize antigens in the absence of suitable costimulatory molecules. By contrast, when the same cell encounters the same ligand on a cell that expresses costimulatory molecules, it will proliferate and differentiate into an effector cell. These effector cells mediate protective immunity when the antigen is carried by a pathogen, but they can mount autoimmune responses if the antigen is derived from self. The major costimulatory molecules for CD4 T cells appear to be B7 and B7.2 that bind to the CD28 and CTLA-4 receptors on the T cell. The signals from the TCR appear to be integrated with those from the costimulator receptor, and the T cell response depends on the precise nature of these signals, further conditioned by cytokines present in the environment of the responding cell. B cells can be viewed in a similar way, with the costimulatory molecule CD40 ligand and cytokines coming mainly from CD4 helper T cells determining the fate of the responding B cell. The TCR is not simply an on and off switch, since the precise way in which the TCR is ligated determines the differentiation of the T cell and can alter the effector responses of established T cell lines. Thus, the response capabilities of T cells are more flexible than originally believed, and much of this flexibility comes from the interplay of TCR signals and signs from the environment. If the biochemical nature of these differential signaling pathways were known, it might be possible to develop simple pharmacological agents capable of diverting T cell responses from harmful to innocuous by getting the T cell to reinterpret the signals it is receiving via its receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2025

Distinct rates of VUS reclassification are observed when subclassifying VUS by evidence level.

PURPOSE: Genetic testing commonly yields a plethora of variants of uncertain significance (VUS) that can lead to ongoing uncertainty for patients and their caregivers. Although all VUS hold uncertainty, some VUS have more evidence in support of pathogenicity, whereas others have more evidence of a benign role. Sharing these nuances can help guide the investment in follow-up clinical and research investigations and may, at times, influence medical decision making despite appreciated uncertainty. METHODS: Four clinical laboratories have been subclassifying VUS to help prioritize investigation and guide reporting decisions. Each laboratory developed a distinct approach for how these subclasses are used in their laboratories and, in some cases, displayed on reports. We examined the composition of each laboratory's VUS subclasses and the likelihood variants from each subclass were reclassified toward pathogenic or benign. RESULTS: We found that variants in the lowest subclass of VUS were never reclassified as likely pathogenic or pathogenic, whereas those in the highest subclass were much more likely to be reclassified as pathogenic or likely pathogenic. CONCLUSION: Given that forthcoming professional guidance in variant classification will advise the use of VUS subclasses, the experience of our laboratories in using VUS subclasses can inform future practices.

Humans↗

PubMedDate not supplied

In vivo evaluation of the pathogenicity of field isolates of infectious bronchitis virus.

The pathogenicity of 13 field isolates of infectious bronchitis virus (IBV) isolated from Georgia broiler farms from 1989 to 1992 was evaluated using the IBV and Escherichia coli mixed-infection model. Based on the clinical signs, mortality, and lesions, the isolates were classified as high, intermediate, and low in pathogenicity. The in vivo classification was compared with the serotype classification results obtained by reverse transcriptase-polymerase chain reaction-restriction fragment length polymorphism analysis. The high-pathogenicity group was composed of five isolates representing three serotypes: Arkansas, Georgia variant (GAV), and Massachusetts. Isolates in the intermediate- and low-pathogenicity groups were all representatives of the Connecticut serotype, except for one isolate, which belonged to the Massachusetts serotype.

Animals↗

PubMed2026

Genomic surveillance of enterovirus D68 circulating in 2025 reveals the emergence of a novel A2/B3 recombinant lineage.

Enterovirus D68 (EV-D68) has re-emerged over the past decade as a significant respiratory pathogen associated with severe respiratory disease and acute flaccid myelitis. Its circulation has typically followed a biennial pattern, with predominance in late summer and early fall, a pattern that was temporarily disrupted during the COVID-19 pandemic. Surveillance in 2025 revealed off-season circulation of EV-D68. This study describes the genomic characteristics of the 2025 EV-D68 viruses and the clinical features of affected patients. Between May and December 2025, remnant respiratory specimens positive for rhinovirus/enterovirus were screened for EV-D68 and subjected to whole-genome sequencing. Phylogenetic analyses were performed using maximum-likelihood methods. Recombination was assessed using subgenomic phylogenies, SimPlot similarity and BootScan analyses, and read-level inspection. Among 1,321 patients tested, 147 (11.1%) were EV-D68-positive, and 119 (81.0%) yielded complete genomes. EV-D68 positivity increased in July 2025, peaked in August (~21%), and remained elevated through September and October, exceeding levels observed in 2024. Patients had a median age of 36 years, with infections disproportionately affecting older adults. Phylogenetic analysis demonstrated exclusive circulation of subclade A2. Five genomes formed a distinct recombinant lineage (A2-Re). Subgenomic phylogenies showed clustering with A2 viruses in the P1 region and with B3 viruses in the P2-P3 regions. SimPlot and BootScan analyses identified a recombination breakpoint near the 2A/2B junction (~nt 3,700). The recombinant lineage was associated with temporally clustered cases in September-October. These findings demonstrate recombination between distinct EV-D68 subclades and underscore the importance of whole-genome surveillance for accurate viral characterization. Continued genomic monitoring is essential for detecting emerging variants with potential implications for transmissibility, pathogenicity, and public health preparedness.IMPORTANCEThis study highlights an increased off-season circulation of Enterovirus D68 (EV-D68) and a higher burden of disease in adults in 2025. The identification of a novel A2-B3 recombinant lineage provides evidence of ongoing viral evolution through recombination, a mechanism that may alter transmissibility, virulence, or immune responses. Detection of this lineage in temporally clustered cases suggests local transmission and underscores the potential for rapid spread of newly emerged variants. These findings emphasize the limitations of partial genomic approaches and the critical role of whole-genome sequencing in accurately characterizing circulating strains and identifying recombination events. Enhanced genomic surveillance is essential to detect emerging variants in real time, inform diagnostic assay performance, and support public health responses. Continued monitoring of EV-D68 evolution will be important for anticipating changes in disease burden, guiding clinical awareness, and strengthening preparedness for future outbreaks.

Humans↗

PubMed2026

De novo chromatin remodelling variants in sporadic Chiari 1 malformation.

Chiari 1 malformation (CM1) is the most common congenital malformation of the human hindbrain. Although prior studies have implicated chromatin-remodeling genes in CM1, the de novo genetic architecture and underlying neurodevelopmental mechanisms remain incompletely defined. To investigate the molecular genetics of a novel familial form of CM1 linked with syringomyelia and tethered cord and determine whether rare, damaging de novo variants (DNVs) contribute to sporadic CM1 risk with gene- and pathway-level resolution, we performed whole-exome sequencing in an ultra-rare multigenerational family with CM1 and associated spinal pathology, and in the largest assembled trio-based cohort to date, comprising 1,585 proband-parent trios with sporadic, idiopathic CM1 (2017-2025). The comparison cohort included 1,798 unaffected control siblings. Clinical phenotyping was by systematic medical record review. Structural domain mapping, in silico modeling, and integration with single-cell transcriptomic data from developing human cerebellum was conducted to assess biological plausibility. A heterozygous loss-of-function variant in CHD3 segregated with CM1 and syringomyelia in a multigenerational family. In the trio-based cohort, rare protein-altering DNVs were significantly enriched across multiple chromodomain helicase DNA-binding (CHD) genes, including CHD1, CHD3, CHD4, and CHD8, exceeding gene-specific mutation expectations (protein-damaging variants: P = 1.3 × 10-9; predicted loss-of-function variants: P = 8.6 × 10-5). CHD1 contained two pathogenic DNVs (p.A999D and p.E984K). CHD4 (p.D744N, p.T1813P, and p.I1102T) and CHD8 (p.R1402X, p.R1472X, and p.R2035X) each contained three new DNVs. Variants clustered within conserved ATPase, helicase, and chromodomain regions essential for chromatin remodeling, and these patients frequently had comorbid developmental delay and related neurodevelopmental features. Single-cell transcriptomic analyses demonstrated enrichment in Purkinje cells and inhibitory neurons of midgestational cerebellum, where CHD gene products form a coherent chromatin-regulatory network. Rare, large-effect DNVs that disrupt chromatin-remodeling programs contribute to sporadic CM1, implicating genetically encoded dysregulation of cerebellar development as a central disease mechanism. Exome sequencing may complement surgical evaluation of children with sporadic CM1, particularly when accompanied by neurodevelopmental concerns, informing prognosis and family counseling.

de novo variants↗

PubMed2024

Bioinformatics pipeline for the systematic mining genomic and proteomic variation linked to rare diseases: The example of monogenic diabetes.

Monogenic diabetes is characterized as a group of diseases caused by rare variants in single genes. Like for other rare diseases, multiple genes have been linked to monogenic diabetes with different measures of pathogenicity, but the information on the genes and variants is not unified among different resources, making it challenging to process them informatically. We have developed an automated pipeline for collecting and harmonizing data on genetic variants linked to monogenic diabetes. Furthermore, we have translated variant genetic sequences into protein sequences accounting for all protein isoforms and their variants. This allows researchers to consolidate information on variant genes and proteins linked to monogenic diabetes and facilitates their study using proteomics or structural biology. Our open and flexible implementation using Jupyter notebooks enables tailoring and modifying the pipeline and its application to other rare diseases.

Humans↗

PubMed1988

An outbreak of acute hemorrhagic conjunctivitis due to Coxsackie virus type A24 variant in Japan.

An outbreak of acute conjunctivitis due to Coxsackie virus A24 (CA24) occurred in Okinawa, the southernmost island of Japan, from 1985 to 1986. From conjunctival scrapings of 85 acute hemorrhagic conjunctivitis patients, 39 isolates identified as an antigenic variant of CA24 were obtained and then cultured in HeLa cells. Paired sera taken from these patients with acute conjunctivitis in Okinawa were also tested against enterovirus 70 (EV70) and CA24 and showed rises in neutralizing antibodies to these agents. The subconjunctival hemorrhage among the clinical manifestations caused by the CA24 variant in this recent epidemic was similar to that due to EV70. EV70 conjunctivitis is more commonly known as acute hemorrhagic conjunctivitis (AHC), first named by the Japanese ophthalmologist, Prof. Seiji Sugiura. The present seroepidemiologic survey for the CA24 variant and EV70 in different districts of Japan revealed a low frequency of rise in neutralizing antibody titers against these two pathogens. The differentiation between EV70 and the CA24 variant as the agent causing AHC is very important in epidemiology, especially as there is a high possibility in Japan of outbreaks caused by these two agents.

Adolescent↗

PubMed2000

Predominance of one T-cell antigen receptor BV haplotype in African populations.

The human T-cell antigen receptor (TCR) is the counter-receptor for the HLA/peptide complex displayed on the surface of antigen-presenting cells. It confers antigen specificity on T lymphocytes and therefore plays a central role in pathogen recognition and host response. The most frequently used form of the TCR is a heterodimer composed of variable alpha and beta chains. We investigated allele frequencies for four variable-region gene segments of the beta chain (2S1, 3S1, 8S3, and 15S1) in 146 Caucasians and 165 Africans. The results reveal significant unexpected differences between the two populations for allele frequencies, phenotypes, genotypes, and haplotypes. Among Caucasians, there are 43 phenotypes, whereas there are 31 among the Africans studied. There are 17 haplotypes in the Caucasian sample but only 10 in Africans. This loss of diversity is largely due to the high frequency of one haplotype in the African sample which represents 65% of the informative chromosomes. At least one copy of this haplotype is present in 90% of informative individuals. As a result, 29% of Africans are homozygous for the common haplotype. Less genetic diversity at TCRBV is unexpected, since Africans usually show greater genetic diversity than other ethnic groups. For example, there are approximately twice as many HLA haplotypes in Africans compared to Caucasians. Homozygosity is also unexpected because it reduces the number of TCR variants available to recognize HLA pathogen-derived peptide complexes.

Alleles↗

PubMed1993

[Epidemiology of drug resistance in pathogens isolated in hospitals].

A 20-year observation showed that there were significant changes in the species composition and ratio of the sensitive and resistant variants of opportunistic bacteria constituting the main part of the pathogens causing infectious complications in somatic hospitals. However, the taxonomic structure of the pathogens changed slowly, perhaps due to the ever increasing role of the hospital strains in the development of the infections in the inpatients. The higher number of the resistant variants primarily depended on the rate of the drug use, as well as on the biological and physiological properties of the bacteria, the structure of the drugs, the nature of the resistance, etc. Therefore, the following up of the species composition of the pathogens for estimating the role of every taxon in the development of the infections with their particular localization and the determining of the relative number of the strains sensitive to the drugs used in the hospitals are the obligatory conditions for rational antibacterial chemotherapy.

Bacteria↗

PubMed1989

Harvey murine sarcoma virus: influences of coding and noncoding sequences on cell transformation in vitro and oncogenicity in vivo.

The rat-derived Harvey murine sarcoma virus (Ha-MuSV) contains a transduced ras oncogene activated by two missense mutations and flanked by rat retroviruslike VL30 sequences. Ha-MuSV induces focal transformation of mouse NIH 3T3 cells in vitro and tumors (fibrosarcomas and splenic erythroleukemias) in newborn mice. We have used these two assays to study the contribution of coding and noncoding viral sequences to the biological activity of Ha-MuSV. A good correlation was found between the in vitro and in vivo assays. In several different isogenic Ha-MuSV variants, those with a rasH gene that had one or both of the Ha-MuSV missense mutations were much more active biologically than the corresponding proto-oncogene. A Ha-MuSV variant that encoded the proto-oncogene protein induced lymphoid leukemias (with thymomas), with a relatively long latent period, rather than the fibrosarcomas and erythroleukemias characteristic of Ha-MuSV with one or both missense mutations. A VL30-derived segment with enhancer activity was identified downstream from v-rasH. A mutant Ha-MuSV from which this 3' noncoding segment was deleted expressed lower levels of the wild-type viral protein, displayed impaired transforming activity in vitro, and induced lymphoid leukemias (with thymomas). 5' noncoding rat c-rasH sequences were found to increase the biological activity of the virus when substituted for the corresponding segment of v-rasH. We conclude that (i) the biological activity of Ha-MuSV can be influence significantly by noncoding sequences located outside the long terminal repeat as well as by coding sequences, (ii) VL30 sequences positively regulate the expression of v-rasH, (iii) relatively low biological levels of ras, whether resulting from low-level expression of wild type v-rasH or high-levels of ras proto-oncogene protein, induce a type of tumor that differs from tumors induced by high biological levels of ras, and (iv) the in vivo pathogenicity of the Ha-MuSV variants correlated with their transforming activity on NIH 3T3 cells.

Animals↗

PubMed2005

Tandem repeat copy-number variation in protein-coding regions of human genes.

BACKGROUND: Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles. RESULTS: Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term 'protein-binding' remained significant after covariate adjustment and correction for multiple testing. Combining this analysis with previous experimental evaluations of tandem repeat polymorphism, we estimate the approximate mean frequency of tandem repeat polymorphisms in human proteins to be 6%. Because 13.9% of the polymorphisms were not a multiple of three nucleotides, up to 1% of proteins may contain frameshifting tandem repeat polymorphisms. CONCLUSION: Around 1 in 20 human proteins are likely to contain tandem repeat copy-number polymorphisms within coding regions. Such polymorphisms are not more frequent among defense-response proteins; their prevalence among protein-binding proteins may reflect lower selective constraints on their structural modification. The impact of frameshifting and longer copy-number variants on protein function and disease merits further investigation.

Frameshift Mutation↗

PubMed2001

Expression of Anaplasma marginale major surface protein 2 variants in persistently infected ticks.

Anaplasma marginale, an intraerythrocytic ehrlichial pathogen of cattle, establishes persistent infections in both vertebrate (cattle) and invertebrate (tick) hosts. The ability of A. marginale to persist in cattle has been shown to be due, in part, to major surface protein 2 (MSP2) variants which are hypothesized to emerge in response to the bovine immune response. MSP2 antigenic variation has not been studied in persistently infected ticks. In this study we analyzed MSP2 in A. marginale populations from the salivary glands of male Dermacentor variabilis persistently infected with A. marginale after feeding successively on one susceptible bovine and three sheep. New MSP2 variants appeared in each A. marginale population, and sequence alignment of the MSP2 variants revealed multiple amino acid substitutions, insertions, and deletions. These results suggest that selection pressure on MSP2 occurred in tick salivary glands independent of the bovine immune response.

Amino Acid Sequence↗

PubMed2003

Standard and Swedish variant types of the hybrid alder Phytophthora attacking alder in Hungary.

A new Phytophthora disease of common alder (Alnus glutinosa) similar to that previously reported in several countries in Europe has been observed in Hungary. Based on these earlier studies, the alder Phytophthora was considered likely to be a hybrid between P cambivora and a P fragariae-like species: across Europe a range of new alder Phytophthora is spreading that comprise a range of heteroploid hybrids including a 'standard' hybrid type and several other hybrid types termed 'variants'. Phenotypic and molecular features of the pathogen in Hungary were characterised and compared with isolates from elsewhere. The morphologies of five isolates from one region (Hévíz) resembled the common, 'standard' type, whereas the three isolates from another region (Hanság) exhibited traits similar to those of one of the 'variant' types, ie the Swedish 'variant'. Molecular markers of these two groups of Hungarian isolates also represented a good fit to those of the standard type and the Swedish variant, respectively. Isozyme patterns and profiles of restriction fragments of the entire internal transcribed spacer (ITS) region or mitochondrial DNAs and of RAPD-PCR products did not differ within a group, but distinct polymorphisms were exhibited between the two groups of isolates. Southern analysis of random amplified polymorphic DNA (RAPD) revealed the homologous nature of co-migrating bands of P cambivora and the isolates of alder Phytophthora. Furthermore, restriction fragment profiles of the ITS region of ribosomal DNAs and the mtDNAs were consistent with reported biparental origin of alder Phytophthora. The hybrid status of these continuously evolving pathogens raises many issues and challenges concerning efficient control measures.

Alnus↗