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PubMed1991

Long-range restriction maps of size-variable homologous chromosomes in Leishmania infantum.

In order to clarify the interpretation of molecular karyotype polymorphisms in Leishmania, the three smallest chromosomes from five cloned strains of Leishmania infantum were identified by chromosome-specific anonymous DNA probes. The presence in the same clone of homologous chromosomes of a different size was demonstrated. The chromosome size polymorphism appeared even more dramatic, with size variations affecting up to 20% of the chromosome, and the two smallest bands in one strain being equivalent to six bands in another strain. Long-range restriction maps of five different-sized homologues of chromosome I showed the size-variation to be located to a terminal fragment in 4 out of 5 cases, and to a central fragment in one. The size-variable sequence was present on at least three other chromosomes as determined by hybridisation analysis. This suggests an instability of the subtelomeric regions such as that in Plasmodium falciparum. Lastly, the finding of several pairs of distinct-sized homologous chromosomes, together with other studies, strongly suggest that Leishmania is diploid in at least part of its chromosomal complement.

Animals↗
PubMed1997

Clinical relevance of Fc gamma receptor polymorphisms.

Human IgG receptors are very heterogeneous and we currently distinguish three Fc gamma receptor classes specifying at least 12 receptor isoforms. On top of this complexity, Fc gamma R are further found to differ between different individuals. Polymorphisms have been identified for all three Fc gamma R classes. The best-studied ones represent allelic variation of Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16). The Fc gamma RIIa polymorphism is now considered to be a heritable risk factor for autoimmune and infectious diseases, and support for a relevant role of the IIIb polymorphism has also been obtained. A detailed analysis of the exact contribution of each of these Fc gamma R polymorphisms in relation to previously implicated risk factors should unravel the pathophysiological importance of Fc gamma R polymorphisms in the near future.

Animals↗
PubMed2003

Associations of a polymorphic AP-2 binding site in the 5'-flanking region of the bovine beta-lactoglobulin gene with milk proteins.

Studies on a polymorphic position (R10) in an Activator-Protein-2 (AP-2) binding site of the bovine beta-Lactoglobulin (beta-Lg) gene promoter region and quantitative traits of individual milk proteins were based on material from 79 German Holstein Friesian (HF) and 61 Simmental (Sm) cows. At least four milk samples per cow were analyzed with alkaline Urea-PAGE in combination with densitometry for quantification of individual milk proteins. The two alleles of the R10 single nucleotide polymorphism (SNP) carry either G or C in position -435 bp of the beta-Lg promoter region. G- and C-alleles were found in Sm with nearly equal frequencies, while in HF the C-allele frequency was higher (0.73) than that of the G-allele. In both breeds, the R10 G-homozygotes had higher (P < 0.001) amounts of beta-Lg secreted per day and proportion of beta-Lg in milk protein compared with the C-homozygotes. A similar association was found for alpha-lactalbumin, whereas the relative proportions and daily secreted amounts of caseins (alphaS1, beta, kappa) showed lower values in beta-Lg R10 G-homozygotes. A positive association (P < 0.001) of R10 CC with milk yield has also been observed and indicates a close proximity of the beta-Lg locus to a candidate gene for this trait. The association between the SNP in the AP-2 binding site of the beta-Lg gene and its gene product can be explained as the result of differences in protein binding activity, and, therefore, allele specific differences in gene expression. Thus, our study clearly links a DNA polymorphism of molecular function very closely with in vivo expression parameters of the same locus.

Alleles↗
PubMed2006

Air quality biomonitoring: assessment of air pollution genotoxicity in the Province of Novara (North Italy) by using Trifolium repens L. and molecular markers.

Mixed air pollutants are considered a major cause of DNA damage in living species. In this study Trifolium repens L. cv Regal was used as a bioindicator to assess the genotoxicity of air stressors in the Italian province of Novara. Two on-site biomonitoring experiments were performed during the spring and autumn of 2004. Test plants were exposed at 19 monitoring sites distributed homogeneously throughout the province, and each experiment lasted for a period of 6 weeks. Genotoxicity was evaluated with Amplified Fragment Length Polymorphism (AFLP) molecular markers. The results show the predominantly rural central-west region of the Novara Province to have the worst air quality with regard to genotoxicity. Analyses of geomorphology, land use and climatic factors suggest that the compromised air quality in the region could be attributed to wind strength and direction, transporting pollution from vehicular traffic on the A4 highway and from the urban/industrialized centres of Novara and Vercelli. Plant growth, changes in plant photochemical efficiency and the presence of ozone related leaf injuries were also measured to better interpret the results of genotoxicity. Statistical analyses show that although climatic factors such as light intensity and temperature influence plant growth, they do not contribute to atmospheric stressor-induced DNA damage. Further analyses indicated that, as expected, a mixture of genotoxic and non-genotoxic pollutants coexist in the Novara Province troposphere, and that the elevated ozone concentrations experienced during the study may have contributed to the DNA damage in the tested plants by enhancing genotoxicity via interaction with other air stressors.

Air Pollutants↗
PubMed2006

[Amplified fragment length polymorphism genotyping of Shigellae and comparison to pulsed-field gel electrophoresis and colicin typing].

Shigella is an etiological agent of communicable and food-borne disease worldwide, so it is important to develop typing for Shigella in epidemiological studies. We compared amplified fragment length polymorphism (AFLP), molecular epidemiological typing, to pulsed-field gel electrophoresis (PFGE) and colicin typing in typeability, reproducibility, discriminatory power, ease of interpretation, and ease of use for 51 Shigella isolates to determine AFLP applicability to Shigella. AFLP showed less reproducibility and ease of interpretation although it was superior to PFGE and colicin typing in typeability and discriminatory power. Specifying the reproducibility of these typing methods, the intrastrain similarity of AFLP was 81.9%-90.5% in each of three strains tested in triplicate trials, while PFGE showed higher similarity, ranging from 92.3%-100%. AFLP created a phylogenetic tree and classified four Shigella species taxonomically, despite its lower reproducibility. These results suggest that AFLP is inferior to PFGE as molecular typing for Shigella epidemiologically in outbreaks or sporadic cases, although AFLP can create a phylogenetic tree for taxonomical purposes.

Bacterial Typing Techniques↗
PubMed2000

Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP.

Polymorphisms in the prion protein (PrP) gene are associated with phenotypic expression differences of transmissible spongiform encephalopathies in animals and humans. In sheep, at least 10 different mutually exclusive polymorphisms are present in PrP. In this study, we determined the efficiency of the in vitro formation of protease-resistant PrP of nine sheep PrP allelic variants in order to gauge the relative susceptibility of sheep for scrapie. No detectable spontaneous protease-resistant PrP formation occurred under the cell-free conditions used. All nine host-encoded cellular PrP (PrP(C)) variants had distinct conversion efficiencies induced by PrP(Sc) isolated from sheep with three different homozygous PrP genotypes. In general, PrP allelic variants with polymorphisms at either codon 136 (Ala to Val) or codon 141 (Leu to Phe) and phylogenetic wild-type sheep PrP(C) converted with highest efficiency to protease-resistant forms, which indicates a linkage with a high susceptibility of sheep for scrapie. PrP(C) variants with polymorphisms at codons 171 (Gln to Arg), 154 (Arg to His), and to a minor extent 112 (Met to Thr) converted with low efficiency to protease-resistant isoforms. This finding indicates a linkage of these alleles with a reduced susceptibility or resistance for scrapie. In addition, PrP(Sc) with the codon 171 (Gln-to-His) polymorphism is the first variant reported to induce higher conversion efficiencies with heterologous rather than homologous PrP variants. The results of this study strengthen our views on polymorphism barriers and have further implications for scrapie control programs by breeding strategies.

Alleles↗
PubMed1991

Molecular cloning and deoxyribonucleic acid polymorphisms in Lactobacillus acidophilus and Lactobacillus gasseri.

Lactobacillus strain ADH is a bile-resistant, bacteriocin-producing human isolate that was phenotypically classified within the Lactobacillus acidophilus group. Total DNA and phage DNA extracted from strain ADH were separately digested with BclI and ligated with BclI-digested pGK12. Following electroporation of these ligation mixtures directly into strain ADH, electrotransformants were recovered at frequencies of 1.5 x 10(3) and 2.0 x 10(4)/micrograms of pGK12 for preparations of pGK12::phage DNA and pGK12::total DNA, respectively. Among the electrotransformants screened, 6 and 22% contained passenger DNA of either phage DNA or chromosomal origin, respectively, as determined by restriction-enzyme analyses and hybridization assays. Derivatives of pGK12 containing passenger DNA of chromosomal (pTRK120) or phage (pTRK121) origin and pTRK15 (native cryptic plasmid) were evaluated for use as species-specific probes. The strain ADH-derived probes hybridized primarily to members of the B-1 and B-2 lactobacilli homology groups and demonstrated strain-specific polymorphisms within these groups. Identical hybridization patterns were established for strain ADH and Lactobacillus gasseri VPI 6033 (ATCC 19992). Identification of DNA probes and establishment of a host-vector cloning system have facilitated our efforts to characterize the Lactobacillus chromosome and to distinguish between closely related species thought to be important inhabitants of the gastrointestinal tract.

Chromosomes, Bacterial↗
PubMed1998

[Polymorphism of the renin-angiotensin-aldosterone system: molecular and epidemiogenetic aspects].

The involvement of polymorphic variations in the structure of the renin angiotensin aldosterone system genes in the predisposition to cardiovascular disease is a particularly important field of investigation. A large number of studies have been published and their results are often contradictory. It is therefore important to identify the functional variants modifying the level of expression of these genes or the structure of the encoded proteins. This will allow the clear quantitation of their effect on quantitative phenotypes both in vitro and in vivo. It is also important to study in the future new phenotypes, particularly dynamic phenotypes, potentially influenced by these genotypes and to use them for building a new cardio-vascular pharmacogenetics.

Aldosterone↗
PubMed1989

Polymorphism in the assembly of polyomavirus capsid protein VP1.

Polyomavirus major capsid protein VP1, purified after expression of the recombinant gene in Escherichia coli, forms stable pentamers in low-ionic strength, neutral, or alkaline solutions. Electron microscopy showed that the pentamers, which correspond to viral capsomeres, can be self-assembled into a variety of polymorphic aggregates by lowering the pH, adding calcium, or raising the ionic strength. Some of the aggregates resembled the 500-A-diameter virus capsid, whereas other considerably larger or smaller capsids were also produced. The particular structures formed on transition to an environment favoring assembly depended on the pathway of the solvent changes as well as on the final conditions. Mass measurements from cryoelectron micrographs and image analysis of negatively stained specimens established that a distinctive 320-A-diameter particle consists of 24 close-packed pentamers arranged with octahedral symmetry. Comparison of this unexpected octahedral assembly with a 12-capsomere icosahedral aggregate and the 72-capsomere icosahedral virus capsid by computer graphics methods indicates that similar connections are made among trimers of pentamers in these shells of different size. The polymorphism in the assembly of VP1 pentamers can be related to the switching in bonding specificity required to build the virus capsid.

Capsid↗
PubMed1990

Efficiency of marker-assisted selection in the improvement of quantitative traits.

Molecular genetics can be integrated with traditional methods of artificial selection on phenotypes by applying marker-assisted selection (MAS). We derive selection indices that maximize the rate of improvement in quantitative characters under different schemes of MAS combining information on molecular genetic polymorphisms (marker loci) with data on phenotypic variation among individuals (and their relatives). We also analyze statistical limitations on the efficiency of MAS, including the detectability of associations between marker loci and quantitative trait loci, and sampling errors in estimating the weighting coefficients in the selection index. The efficiency of artificial selection can be increased substantially using MAS following hybridization of selected lines. This requires initially scoring genotypes at a few hundred molecular marker loci, as well as phenotypic traits, on a few hundred to a few thousand individuals; the number of marker loci scored can be greatly reduced in later generations. The increase in selection efficiency from the use of marker loci, and the sample sizes necessary to achieve them, depend on the genetic parameters and the selection scheme.

Animals↗
PubMed1997

Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk.

We analyzed the polymorphic (CAG)n and (GGN)n regions within the androgen receptor gene from participants in a population-based case-control study of prostate cancer in middle-aged (40-64 years) Caucasian men. The associations between repeat lengths and risk of prostate cancer and the effects of confounding and modifying factors, such as age, family history of prostate cancer, and body mass index, were evaluated. DNA was available for 301 cases and 277 controls. The overall age-adjusted relative odds of prostate cancer associated with the number of (CAG) repeats as a continuous variable was 0.97 [95% confidence interval (CI), 0.92-1.03], suggesting a 3% decrease in risk of prostate cancer for each additional (CAG) repeat. Further analyses identified several subgroups at increased risk. These were men with less than the median number of CAG repeats (< 22) that were younger [< 60 years; relative odds (RO), 1.47; 95% CI, 0.96-2.25], had an affected first-degree relative (RO, 1.59; 95% CI, 0.62-4.14), or were relatively thin (Quetelet index < 24.4; RO, 2.21; 95% CI, 1.07-4.69). Although only the latter result was statistically significant, these results are provocative and support the hypothesis that (CAG)n array length is a predictor of risk for prostate cancer. Similar analyses of (GGN)n showed that with the exception of men with a family history of prostate cancer and those in the highest quartile of body mass index, men with < or = 16 repeats had higher risk estimates than did men with > 16 repeats. Overall, those men who had < or = 16 repeats had a significant elevation in risk (RO, 1.60; 95% CI, 1.07-2.41). When both repeat lengths were considered jointly, the subgroup with two short repeats (CAG, < 22; GGN, < or = 16) had a 2-fold elevation in odds (RO, 2.05; 95% CI, 1.09-3.84) relative to those with two long repeats (CAG, > or = 22; GGN, > 16). These data suggest that determination of both androgen receptor repeats within germ-line DNA may be useful in assessing an individual's risk of developing prostate cancer.

Adenocarcinoma↗
PubMed2006

Genetic variability in species of bats revealed by RAPD analysis.

Random amplified polymorphic DNA molecular marker was utilized as a means of analyzing genetic variability in seven bat species: Molossus molossus, M. rufus, Eumops glaucinus, E. perotis, Myotis nigricans, Eptesicus furinalis, and Artibeus planirostris. The determination of genetic diversity was based on 741 bands produced by a 20-random primer set. Only eight bands were considered monomorphic to one species. The greatest number of bands and the most polymorphic condition were exhibited by M. molossus, followed by M. nigricans, A. planirostris, E. furinalis, E. glaucinus, M. rufus, and E. perotis. Nei's genetic diversity index in the seven species considering the 20 primers was not greater than 0.22, but some primers were capable of detecting values between 0.39 and 0.49. Nei's unbiased genetic distance values and the UPGMA clustering pattern show that M. molossus and M. rufus have a close genetic relationship, unlike that observed between E. perotis and E. glaucinus. The latter was clustered with A. planirostris and E. furinalis. The low values for genetic diversity and distance observed indicate a genetic conservatism in the seven species. The fluorescent in situ hybridization experiments did not confirm a monomorphic condition for the eight bands identified, demonstrating that the monomorphic bands obtained by random amplified polymorphic DNA are insufficient for the identification of bat species.

Animals↗
PubMed2001

Structural polymorphism of the major capsid protein of rotavirus.

Rotaviruses are important human pathogens with a triple-layered icosahedral capsid. The major capsid protein VP6 is shown here to self-assemble into spherical or helical particles mainly depending upon pH. Assembly is inhibited either by low pH (<3.0) or by a high concentration (>100 mM) of divalent cations (Ca(2+) and Zn(2+)). The structures of two types of helical tubes were determined by electron cryomicroscopy and image analysis to a resolution of 2.0 and 2.5 nm. In both reconstructions, the molecular envelope of VP6 fits the atomic model determined by X-ray crystallography remarkably well. The 3-fold symmetry of the VP6 trimer, being incompatible with the helical symmetry, is broken at the level of the trimer contacts. One type of contact is maintained within all VP6 particles (tubes and virus), strongly suggesting that VP6 assemblies arise from different packings of a unique dimer of trimers. Our data show that the protonation state and thus the charge distribution are important switches governing the assembly of macromolecular assemblies.

Antigens, Viral↗
PubMed2002

Crystal structure of human L-isoaspartyl methyltransferase.

The enzyme l-isoaspartyl methyltransferase initiates the repair of damaged proteins by recognizing and methylating isomerized and racemized aspartyl residues in aging proteins. The crystal structure of the human enzyme containing a bound S-adenosyl-l-homocysteine cofactor is reported here at a resolution of 2.1 A. A comparison of the human enzyme to homologs from two other species reveals several significant differences among otherwise similar structures. In all three structures, we find that three conserved charged residues are buried in the protein interior near the active site. Electrostatics calculations suggest that these buried charges might make significant contributions to the energetics of binding the charged S-adenosyl-l-methionine cofactor and to catalysis. We suggest a possible structural explanation for the observed differences in reactivity toward the structurally similar l-isoaspartyl and d-aspartyl residues in the human, archael, and eubacterial enzymes. Finally, the human structure reveals that the known genetic polymorphism at residue 119 (Val/Ile) maps to an exposed region away from the active site.

Binding Sites↗
PubMed2003

The architecture of the GroEL-GroES-(ADP)(7) chaperonin complex. II. Heptagrammal characterization of the folding.

The heptagrammal forms derived in part I [Janner (2003a). Acta Cryst. D59, 783-794] enclose chain segments of symmetry-related monomers in the GroEL-GroES-(ADP)(7) chaperonin complex. A chain reaching the boundary of a given form either ends, proceeds to a neighbouring form or has to fold. C(alpha) atoms corresponding to these folding points are identified in each of the nine forms of the chaperonin and are approximated by ideal positions having integral coordinates (the indices) with respect to a symmetry-adapted basis. Mutual structural relations between the indexed positions are derived in terms of integral scale-rotations (similar to those that leave the form invariant). The magnesium ions at the binding sites of the nucleotides ADP and ATP are shown to be symmetry-related to these folding points. The change in folding (polymorphism) observed in the cis ring of GroEL arising from binding to GroES is discussed. In particular, the form segmentation is conserved in the polymorphic transition. The geometric and algebraic restrictions imposed on the indexed positions and on their structural relations by the integrality condition are presented in an appendix.

Adenosine Diphosphate↗
PubMed1999

Identification, isolation, and characterization of Ole e 7, a new allergen of olive tree pollen.

BACKGROUND: Olive tree (Olea europaea) pollen is an important cause of pollinosis in countries of the Mediterranean area and California. OBJECTIVE: The aim of this study was to identify and purify a new allergen of olive tree pollen. METHODS: Detection of a pollen allergen was done with individual allergic sera by immunoblotting and ELISA tests. Two allergenic fractions were isolated from olive pollen extract by using gel filtration and reverse-phase HPLC. Molecular characterization was achieved by acid hydrolysis and amino acid analysis, as well as by mass spectrometry. Sequencing of the N-terminal end of the allergen was carried out by Edman degradation of the polypeptide chain. Allergenic characterization was performed with sera from subjects with olive allergy by means of ELISA and immunoblotting after SDS-PAGE. RESULTS: The new allergen Ole e 7 exhibits a high degree of polymorphism. Its molecular mass is in the range of 9875 d to 10,297 d. Twenty-one amino acid residues from the N-terminal end of 2 isoforms of the allergen have been sequenced revealing no homology with proteins contained in database banks. Ole e 7 has an average frequency of about 47% in patients with olive allergy. The strategy of purification of Ole e 7 can be useful on the isolation of new allergens. CONCLUSIONS: A new olive pollen allergen of clinical significance has been purified and characterized, contributing to the study of the complete allergogram of the olive tree pollen.

Allergens↗