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PubMed1982

The primary structure of genetic variants of mouse hemoglobin.

The primary structures of the alpha globins from CE/J, DBA/2J, and a stock of Potter's mice were determined to identify the amino acid substitutions associated with the unique isoelectric focusing patterns of these hemoglobins. In addition, the primary structures of the alpha globins from MOL III and PERU mice were studied in search of amino acid substitutions that may not be detected by isoelectric focusing. CE/J hemoglobin contains a unique kind of alpha globin called chain 5. It differs from the single kind of alpha globin (chain 1) in C57BL/6 by having alanine rather than glycine at position 78. DBA/2J hemoglobin has two kinds of alpha globins: one half is like chain 5 and the other half is like chain 1. The hemoglobin from Potter's stock of Mus musculus molossinus also contains chains 1 and 5, but they are expressed at different levels i.e., 80% chain 1 and 20% chain 5. MOL III hemoglobin has a single kind of a alpha globin identical to that in C57BL/6, and PERU hemoglobin contains approximately 40% chain 1 and 60% chain 4. Chains 1 and 4 have different amino acids at positions 25, 62 and 68. These studies confirm that mouse hemoglobins separable by isoelectric focusing, but not by other means of electrophoresis, have substitutions of neutrally charged amino acids in their alpha chains.

Amino Acid Sequence↗
PubMedDate not supplied

[Comparative analysis of variability of various genetic systems in farm animals].

The particularities of the genetic structure formings of the different genetic systems (biochemical and immunogenetic markers) in the breeds, interbreed crosses of sheep and groups of cattle in connections with the locus, breed and the way of the productivity trait selections were described. The uniqueness of the characteristics and forming mechanisms of the genetic structure related with these factors and the inadequacy of the suppositions about them on the genealogical data were discussed.

Alleles↗
PubMed2001

Genetic and structural determinants of virus neutralizing antibodies.

Neutralizing antibodies (Abs) are the principal protective mechanism against disease caused by reinfection with viruses. Ab-mediated neutralization of viruses is a complex process comprising multiple mechanisms. Every structural aspect of Abs is potentially capable of modulating the level of neutralizing activity or the mechanisms of neutralization. The focus of our laboratory is to understand the genetic and structural basis of Ab-mediated neutralization of human viral pathogens. We demonstrated the unexpected finding that virus antigen-binding fragments of Abs (Fabs) mediate potent virus neutralizing effects in vivo. This work has led to a broad investigation of the importance of the genetics, chemistry, and structure of the combining site to the neutralizing activity of antiviral Abs. Ongoing work in our laboratory reveals that effect or functions specified by the Ab isotype such as polymer formation, interactions with complement, interactions with Fc receptors, and the ability to transcytose mucosal epithelia, also modulate the mechanism and level of neutralizing effects mediated by antiviral Abs.

Antibodies, Viral↗
PubMed2004

Genetic population structure of turbot (Scophthalmus maximus L.) supports the presence of multiple hybrid zones for marine fishes in the transition zone between the Baltic Sea and the North Sea.

Genetic population structure of turbot (Scophthalmus maximus L.) in the Northeast Atlantic was investigated using eight highly variable microsatellite loci. In total 706 individuals from eight locations with temporal replicates were assayed, covering an area from the French Bay of Biscay to the Aaland archipelago in the Baltic Sea. In contrast to previous genetic studies of turbot, we found significant genetic differentiation among samples with a maximum pairwise FST of 0.032. Limited or no genetic differentiation was found among samples within the Atlantic/North Sea area and within the Baltic Sea, suggesting high gene flow among populations in these areas. In contrast, there was a sharp cline in genetic differentiation going from the low saline Baltic Sea to the high saline North Sea. The data were explained best by two divergent populations connected by a hybrid zone; however, a mechanical mixing model could not be ruled out. A significant part of the genetic variance could be ascribed to variation among years within locality. Nevertheless, the population structure was relatively stable over time, suggesting that the observed pattern of genetic differentiation is biologically significant. This study suggests that hybrid zones are a common phenomenon for marine fishes in the transition area between the North Sea and the Baltic Sea and highlights the importance of using interspecific comparisons for inferring population structure in high gene flow species such as most marine fishes.

Animals↗
PubMed2004

Highly polymorphic repeat region in the CETP promoter induces unusual DNA structure.

Genetic variation in the human cholesteryl ester transfer protein (CETP) promoter is associated with HDL cholesterol levels and cardiovascular disease with much of the genetic variation in CETP attributed to the promoter region. In this region, there are several single nucleotide polymorphisms as well as a variable length tandem repeat located 1946 base pairs upstream of the CETP transcription start that is highly polymorphic with respect to both length and sequence. There are more than 10 different long alleles and these vary in their repeat structure. We find that the short allele of this repeat is associated with high HDL cholesterol levels in vivo (P<0.0001). In males, this association is independent of the nearby -629 polymorphism. In addition, the variable length GAAA repeat can stimulate an adjacent GGGGA repeat to form a structure that hinders DNA amplification and sequencing. This structure also has an effect in vivo as shown by orientation effects and cloning efficiency in Escherichia coli.

Animals↗
PubMed1994

Population genetics of filamentous fungi.

Population genetics aims to understand causes and consequences of the genetic structure of populations, i.e. distributions of genetic variants in space and time. Among the most important determinants of the genetic population structure is the genetic system itself, which is the collection of processes and mechanisms responsible for the transmission of genetic information. Filamentous fungi offer excellent opportunities for studying the effects of the genetic system on genetic population structure. Apart from their advantage as laboratory organisms, they exhibit a wide variety of genetic systems. In particular, their inherent capacity for anastomosis provides unique possibilities for investigating rates and consequences of horizontal gene transfer. Furthermore, the temporary confinement of the products of meiosis in a common structure (the ascus) enables the study of competitive and antagonistic interactions between the meiotic products. An intriguing example of the latter is the phenomenon of 'spore killing', resulting in distorted meiotic segregation. This paper concentrates on population level research of the occurrence of vegetative incompatibility in Aspergillus and Neurospora species and to what extent this will inhibit horizontal transmission of genetic information, and on spore killing in Podospora anserina.

Biological Evolution↗
PubMed2026

Genomic characterization of KPC-2 and NDM coproducing carbapenem-resistant Klebsiella pneumoniae in a hospital: discovery of ST1869 clone and a novel hybrid plasmid.

UNLABELLED: To characterize the plasmid architecture and molecular background of KPC-NDM coproducing carbapenem-resistant Klebsiella pneumoniae (KN-CRKP) in a South China hospital. Five KN-CRKP isolates were collected, including three from one patient. All underwent Illumina sequencing; two (ST11 and ST1869) additionally had Nanopore sequencing. Antimicrobial susceptibility testing strain sequence types, conjugation assays, resistance gene profiling, plasmid typing, genetic structure comparison, core-genome single nucleotide polymorphisms (SNPs) analysis, and plasmid clustering were performed. All isolates exhibited an imipenem minimum inhibitory concentration (MIC) of &#x2265;128 &#xb5;g/mL and harbored multiple resistance genes. One isolate (1/5) belonged to ST1869 and co-harbored blaKPC-2 and blaNDM-5. The blaNDM-5-carrying plasmid was a novel IncI1/X3 fusion plasmid that also carried blaCMY-42. Unlike several IncX3 plasmids carrying blaNDM in publicly available KN-CRKP genomes from South China, this IncI1/X3 hybrid lacked a complete conjugative transfer system. ST11 was the predominant clone (4/5), co-harboring blaKPC-2 and blaNDM-1. A rare genetic structure, &#x394;ISKpn6-blaKPC-2-ISKpn28, was identified on IncFII plasmids carrying blaKPC-2. Plasmid clustering analysis of 126 comparative KN-CRKP genomes showed diverse sequence types and plasmid backgrounds associated with the KPC/NDM co-production pattern. The observed plasmid diversity and structural variation in KN-CRKP support continued genomic surveillance, with particular attention to the ST1869 clone, the novel IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare "&#x394;ISKpn6-blaKPC-2-ISKpn28" genetic structure. Expanded genomic data on KN-CRKP are needed to further elucidate its resistance mechanisms and plasmid evolutionary trajectories. IMPORTANCE: The co-production of KPC and NDM carbapenemases in Klebsiella pneumoniae poses a formidable threat to clinical antimicrobial therapy, as these enzymes confer resistance to virtually all &#x3b2;-lactam agents, including carbapenems. Here, we report novel genomic features of KN-CRKP in South China, including the emergence of the ST1869 clone, a unique IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare &#x394;ISKpn6-blaKPC-2-ISKpn28 genetic structure. These findings substantially expand current understanding of plasmid evolution and resistance gene dissemination in this region. The identification of diverse resistance mechanisms and clonal backgrounds supports enhanced genomic surveillance and infection-control awareness for pan-resistant Enterobacterales.

Plasmids↗
PubMed2006

Pattern of mitochondrial DNA variation between and within Anopheles stephensi (Diptera: Culicidae) biological forms suggests extensive gene flow.

Anopheles stephensi Liston is the most prevalent anopheline species and plays an important role in malaria transmission in Indian subcontinent and Middle East including southern parts of Iran. It exists as three biological forms; "type", "intermediate", and variety mysorensis. The type form is reported to be an efficient vector of urban malaria, whereas mysorensis and intermediate are considered to be rural species and poor vectors. Moreover, differences in cuticular hydrocarbon and chromosomal characters have been described between urban and rural forms. However, the genetic structure of the biological forms remains unclear. This study was conducted to determine the genetic structure of the An. stephensi biological forms in south of Iran where all three forms are present. Live specimens were collected from the field and transferred to insectaries, reared, and identified based on egg morphological characters. Genetic structure of the biological forms was studied using PCR-RFLP of 1512 bp of mitochondrial DNA (mtDNA) cytochrome oxidase subunit I and II (COI-COII) and sequence of about 712 bp of COI and 562 bp of COII genes. Sequence analysis showed that except for a few substitutions in COII, all three forms and populations were nearly identical. The high homology of COI and COII sequence of An. stephensi forms indicates extensive gene flow between populations and forms in the region. This data will serve as first report on the sequence of mDNA COI-COII of biological forms of An. stephensi, which could be used as a diagnostic tool to identify vector/non-vector, gene flow, and geographical exchanges.

Animals↗
PubMed1992

Decomposition of multivariate phenotypic means in multigroup genetic covariance structure analysis.

Observed differences in phenotypic means between groups such as parents and their offspring or male and female twins can be decomposed into genetic and environmental components. The decomposition is based on the assumption that the difference in phenotypic means is due to a difference in the location of the normal genetic and environmental distributions underlying the phenotypic individual differences. Differences between the groups in variance can be accommodated insofar as they are due to differences in unique variance or can be modeled using a scale parameter. The decomposition may be carried out in the standard analysis of genetic covariance structure using, for instance, LISREL. Illustrations are given using simulated data and twin data relating to blood pressure. Other possible applications are mentioned.

Blood Pressure↗
PubMed2004

Population structure and genetic variability within isolates of Grapevine fanleaf virus from a naturally infected vineyard in France: evidence for mixed infection and recombination.

The nematode-borne Grapevine fanleaf virus, from the genus Nepovirus in the family Comoviridae, causes severe degeneration of grapevines in most vineyards worldwide. We characterized 347 isolates from transgenic and conventional grapevines from two vineyard sites in the Champagne region of France for their molecular variant composition. The population structure and genetic diversity were examined in the coat protein gene by IC-RT-PCR-RFLP analysis with EcoRI and StyI, and nucleotide sequencing, respectively. RFLP data suggested that 55 % (191 of 347) of the isolates had a population structure consisting of one predominant variant. Sequencing data of 51 isolates representing the different restrictotypes confirmed the existence of mixed infection with a frequency of 33 % (17 of 51) and showed two major predominant haplotypes representing 71 % (60 of 85) of the sequence variants. Comparative nucleotide diversity among population subsets implied a lack of genetic differentiation according to host (transgenic vs conventional) or field site for most restrictotypes (17 of 18 and 13 of 18) and for haplotypes in most phylogenetic groups (seven of eight and six of eight), respectively. Interestingly, five of the 85 haplotypes sequenced had an intermediate divergence (0.036-0.066) between the lower (0.005-0.028) and upper range (0.083-0.138) of nucleotide variability, suggesting the occurrence of homologous RNA recombination. Sequence alignments clearly indicated a mosaic structure for four of these five variants, for which recombination sites were identified and parental lineages proposed. This is the first in-depth characterization of the population structure and genetic diversity in a nepovirus.

Base Sequence↗
PubMed2000

Partitioning of peptides and recombinant protein-peptide fusions in thermoseparating aqueous two-phase systems: effect of peptide primary structure.

Genetic engineering has been used for fusion of peptides, with different length and composition, on a protein to study the effect on partitioning in an aqueous two-phase system. The system was composed of dextran and the thermoseparating ethylene oxide-propylene oxide random copolymer, EO30P070. Peptides containing tryptophan, proline, arginine or aspartate residues were fused at the C-terminus of the recombinant protein ZZ-cutinase. The aim was to find effective tags for the lipolytic enzyme cutinase for large-scale extraction. The target protein and peptide tags were partitioned separately and then together in the fusion proteins in order to gain increased understanding of the influence of certain amino acid residues on the partitioning. The salt K2SO4 was used to reduce the charge dependent salt effects on partitioning and to evaluate the contribution to the partition coefficient from the hydrophobic-hydrophilic properties of the amino acid residues. The effect of Trp on peptide partitioning was independent of the difference in primary structure for (Trp)n, (Trp-Pro)n, (Ala-Trp-Trp-Pro)n and was only determined by the number of Trp. The effect of the charged residues, Arg and Asp, was dependent on the surrounding residues, i.e. if they were situated next to Trp or not. The partitioning behaviour observed for the peptides was qualitatively and in some cases also quantitatively the same as for the fusion proteins. The effect of the salts sodium perchlorate and triethylammonium phosphate on the partitioning was also studied. The salt effects observed for the peptides were qualitatively similar to the effects observed for the fusion proteins.

Amino Acid Sequence↗
PubMed2004

Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV).

The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups of isolates associated with rainbow trout aquaculture (Genotype Ia) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also confirmed. Genotype III included marine isolates from around the British Isles in addition to those associated with turbot mariculture, highlighting a continued risk to the development of this industry. Genotype IV consisted of isolates from the marine environment in North America. Taken together, these findings suggest a marine origin of VHSV in rainbow trout aquaculture. The implications of these findings with respect to the future control of VHSV are discussed. The capacity for molecular phylogenetic analysis to resolve complex epidemiological problems is also demonstrated and its likely future importance to disease management issues highlighted.

Animals↗
PubMed2005

Structural and genetic bases of arterial stiffness.

Arterial stiffness has independent predictive value for cardiovascular events. We review data concerning the heritability of arterial stiffness, and propose an integrated view of the structural and genetic determinants of arterial stiffness, based on a candidate gene approach and recent studies on gene expression profile. Arterial stiffness seems to have a genetic component, which is largely independent of the influence of blood pressure and other cardiovascular risk factors. In animal models of essential hypertension (SHR and SHR-SP), structural modifications of the arterial wall include an increase in the number of elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the internal elastic lamina, possibly leading to redistribution of the mechanical load toward elastic materials. These modifications may give rise to mechanisms that explain why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. In monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal genetically determined wall components on arterial stiffness. Such studies have highlighted the role of extracellular matrix signaling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity but also are involved in the control of SMC function. These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material.

Animals↗
PubMed2006

Phylogeography of Ustilago maydis virus H1 in the USA and Mexico.

Ustilago maydis virus H1 (Umv-H1) is a mycovirus that infects Ustilago maydis, a fungal pathogen of maize. As Zea mays was domesticated, it carried with it many associated symbionts, such that the subsequent range expansion and cultivation of maize should have affected maize symbionts' evolutionary history dramatically. Because transmission of Umv-H1 takes place only through cytoplasmic fusion during mating of U. maydis individuals, the population dynamics of U. maydis and maize are expected to affect the population structure of the viral symbiont strongly. Here, the impact of changes in the evolutionary history of U. maydis on that of Umv-H1 was investigated. The high mutation rate of this virus allows inferences to be made about the evolution and divergence of Umv-H1 lineages as a result of the recent changes in U. maydis geographical and genetic structure. The phylogeographical history and genetic structure of Umv-H1 populations in the USA and Mexico were determined by using analyses of viral nucleotide sequence variation. Infection and recombination frequencies, genetic diversity and rates of neutral evolution were also assessed, to make inferences regarding evolutionary processes underlying the population genetic structure of ancestral and descendent populations. The results suggest that Mexico represents the ancestral population of Umv-H1, from which the virus has been carried with U. maydis populations into the USA. Thus, the population dynamics of one symbiont represent a major evolutionary force on the co-evolutionary dynamics of symbiotic partners.

Capsid↗
PubMed2005

Half-sib family structure of Fagus crenata saplings in an old-growth beech-dwarf bamboo forest.

Half-sib family structure of Fagus crenata saplings was examined in an old-growth beech-dwarf bamboo (Sasa spp.) forest using microsatellite genotypes in parentage analysis to identify the half-sib families in two 50 x 50 m plots: one with 36 adults, 641 saplings and no Sasa cover, the other with 21 adults, 61 saplings and Sasa cover. For large proportions of the saplings (44.6% and 75.4%, respectively) both of their parents were found within the same plot, indicating that pollination events frequently involved short-range pollen dispersal, probably because of the high density of adults in the study population. Although almost all of the adults had half-sib families, the number of offspring in the families was highly variable. In the plot with no Sasa cover, the variation in the number of offspring was significantly explained by the size of parents, i.e. the reproductive success is higher for large adults than for small adults. The half-sibs were aggregately distributed around their parents and the distribution overlapped among different half-sib families, which may be due to the limited seed dispersal and overlapping seed shadows of this species. As expected, there was weak genetic structure in the plot. By contrast, in the plot with Sasa cover, the half-sibs were distributed sparsely with a low density, and the degree of genetic structure was very weak. The difference in the half-sib family structure and genetic structure among saplings presumably reflects the difference in density that should be affected by regeneration dynamics associated with environmental conditions.

Demography↗
PubMed2005

Logistic regression protects against population structure in genetic association studies.

We conduct an extensive simulation study to compare the merits of several methods for using null (unlinked) markers to protect against false positives due to cryptic substructure in population-based genetic association studies. The more sophisticated "structured association" methods perform well but are computationally demanding and rely on estimating the correct number of subpopulations. The simple and fast "genomic control" approach can lose power in certain scenarios. We find that procedures based on logistic regression that are flexible, computationally fast, and easy to implement also provide good protection against the effects of cryptic substructure, even though they do not explicitly model the population structure.

Animals↗
PubMed1979

The genetic fine structure of the complex locus aro3 involved in early aromatic amino acid biosynthesis in Schizosaccharomyces pombe.

The complex locus aro3 of Schizosaccharomyces pombe was subjected to genetical fine structure analysis. By comparing the complementation map and the meiotic recombination map, the aro3 locus could be subdivided into the five adjacent subregions A, B, C, D and E. Out of 115 aro3 alleles, 26 nonsense alleles and 30 missense alleles could be identified by the criteria of nonsense suppressor sensitivity and leakiness, respectively. Most alleles with a pleiotropic complementation pattern are of the nonsense type. We conclude from the polarity of the complementation patterns characterising the nonsense alleles that the translation direction proceeds from subregion. A to subregion E. Antipolar effects in complementation are more frequent than in the analogous system of the arom gene cluster of Neurospora crassa.

Alleles↗
PubMed1983

Marital structure and genetic heterogeneity of Ramea Island, Newfoundland.

The population structure of Ramea Island, Newfoundland, is described using surname, marital migration, and serological data. Results presented indicate that Ramea is an open and heterogeneous population. It is shown, however, that this contemporary characterization has a time depth of only three decades and has resulted from a rapid population response to a single historical/economic event.

Alleles↗