A novel polymorphism (471C-->T) in alpha-1-antitrypsin in a patient with asthma.
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Asthma↗
Biomedical subjects
C Gaillard
Publications and source records attributed to C Gaillard.
Identification of epistatic interactions involved in non-insulin-dependent diabetes mellitus in the Otsuka Long-Evans Tokushima Fatty rat.
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. Our present investigation was designed to identify epistatic interactions influencing NIDDM by performing least squares analysis of variance of all pairs of informative markers in 160 F2 progenies bred from an intercross of OLETF and Fischer-344 rats. We identified four interactions between Nidd15/of (chromosome 7) and Nidd16/of (chromosome 14), Nidd15/of and Nidd17/of (chromosome 15), Nidd16/of and Nidd18/of (chromosome 15), and Nidd16/of and Nidd19/of (chromosome 17), which account for a total of approximately 40% of the genetic variation of entire glucose levels after glucose challenge in the F2. The Nidd16/of locus, which is involved in three of four digenic interactions, and the Nidd19/of are likely to correspond to Nidd2/of and Nidd14/of, NIDDM loci previously identified in the F2 by single-QTL model and multiple-QTL model, respectively, while Nidd15/of, Nidd17/of and Nidd18/of loci reflect novel NIDDM loci. An aberrant increase of the entire glucose level due to synergism occurs in the double OLETF homozygote genotype of Nidd15/of and Nidd16/of, and of Nidd16/of and Nidd19/of, as well as in the OLETF homozygote genotypes of Nidd15/of and Nidd16/of, respectively, combined with the heterozygote genotypes of Nidd17/of and Nidd18/of. These findings demonstrate that inter-allelic interactions are likely to be an important component of NIDDM susceptibility.
Animals↗
Estimation of genetic population variables for six radiographic criteria of hip dysplasia in a colony of Labrador Retrievers.
OBJECTIVE: To estimate genetic population variables for 6 radiographic criteria of canine hip dysplasia (CHD). ANIMALS: 664 full- and half-siblings from a colony of Labrador Retrievers. PROCEDURE: Heritability estimates and genetic correlations were calculated for 6 radiographic criteria of CHD. Two evaluation protocols were compared: the grade of the most severely affected hip joint and the sum of the scores for both hip joints. The predictive performance of estimated breeding values was also evaluated. RESULTS: The overall prevalence of CHD (Federation Cynologique Internationale grades C, D, and E) was 29.6%. Median age at radiographic examination was 377 days. Heritability for the total CHD grade, Norberg angle (NA), coverage of the femoral head (COV), craniodorsal acetabular rim (ACR), subchondral bone sclerosis (SUBCH), shape of the femoral head and neck (FHN), and osteoarthritic changes at the insertion site of the joint capsule (JC) was estimated as follows: 0.44, 0.43, 0.46, 0.37, 0.32, 0.21, and 0.05, respectively. Heritability estimates were slightly higher for the sum of the scores for both hip joints. If NA and COV were included as fixed effects in the model for the dependent variables ACR, SUBCH, FHN, and JC , then heritability of these traits significantly decreased (0.08 to 0.15). High scores of NA and COV lead to a significant increase of the scores of the remaining criteria. CONCLUSIONS AND CLINICAL RELEVANCE: Canine hip dysplasia is heritable to a moderate degree. Signs of subluxation revealed the highest heritability estimates. The criteria ACR, SUBCH, FHN, and JC were strongly influenced by NA and COV.
Animals↗
High affinity binding of proteins HMG1 and HMG2 to semicatenated DNA loops.
BACKGROUND: Proteins HMG1 and HMG2 are two of the most abundant non histone proteins in the nucleus of mammalian cells, and contain a domain of homology with many proteins implicated in the control of development, such as the sex-determination factor Sry and the Sox family of proteins. In vitro studies of interactions of HMG1/2 with DNA have shown that these proteins can bind to many unusual DNA structures, in particular to four-way junctions, with binding affinities of 10(7) to 10(9) M(-1). RESULTS: Here we show that HMG1 and HMG2 bind with a much higher affinity, at least 4 orders of magnitude higher, to a new structure, Form X, which consists of a DNA loop closed at its base by a semicatenated DNA junction, forming a DNA hemicatenane. The binding constant of HMG1 to Form X is higher than 5 x 10(12) M(-1), and the half-life of the complex is longer than one hour in vitro. CONCLUSIONS: Of all DNA structures described so far with which HMG1 and HMG2 interact, we have found that Form X, a DNA loop with a semicatenated DNA junction at its base, is the structure with the highest affinity by more than 4 orders of magnitude. This suggests that, if similar structures exist in the cell nucleus, one of the functions of these proteins might be linked to the remarkable property of DNA hemicatenanes to associate two distant regions of the genome in a stable but reversible manner.
Journal Article↗
Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal alpha 7-nicotinic acetylcholine receptor.
Long chain curarimimetic toxins from snake venom bind with high affinities to both muscular type nicotinic acetylcholine receptors (AChRs) (K(d) in the pm range) and neuronal alpha 7-AChRs (K(d) in the nm range). To understand the molecular basis of this dual function, we submitted alpha-cobratoxin (alpha-Cbtx), a typical long chain curarimimetic toxin, to an extensive mutational analysis. By exploring 36 toxin mutants, we found that Trp-25, Asp-27, Phe-29, Arg-33, Arg-36, and Phe-65 are involved in binding to both neuronal and Torpedo (Antil, S., Servent, D., and Ménez, A. (1999) J. Biol. Chem. 274, 34851-34858) AChRs and that some of them (Trp-25, Asp-27, and Arg-33) have similar binding energy contributions for the two receptors. In contrast, Ala-28, Lys-35, and Cys-26-Cys-30 selectively bind to the alpha 7-AChR, whereas Lys-23 and Lys-49 bind solely to the Torpedo AChR. Therefore, alpha-Cbtx binds to two AChR subtypes using both common and specific residues. Double mutant cycle analyses suggested that Arg-33 in alpha-Cbtx is close to Tyr-187 and Pro-193 in the alpha 7 receptor. Since Arg-33 of another curarimimetic toxin is close to the homologous alpha Tyr-190 of the muscular receptor (Ackermann, E. J., Ang, E. T. H., Kanter, J. R., Tsigelny, I., and Taylor, P. (1998) J. Biol. Chem. 273, 10958-10964), toxin binding probably occurs in homologous regions of neuronal and muscular AChRs. However, no coupling was seen between alpha-Cbtx Arg-33 and alpha 7 receptor Trp-54, Leu-118, and Asp-163, in contrast to what was observed in a homologous situation involving another toxin and a muscular receptor (Osaka, H., Malany, S., Molles, B. E., Sine, S. M., and Taylor, P. (2000) J. Biol. Chem. 275, 5478-5484). Therefore, although occurring in homologous regions, the detailed modes of toxin binding to alpha 7 and muscular receptors are likely to be different. These data offer a molecular basis for the design of toxins with predetermined specificities for various members of the AChR family.
Animals↗
DNA loops and semicatenated DNA junctions.
BACKGROUND: Alternative DNA conformations are of particular interest as potential signals to mark important sites on the genome. The structural variability of CA microsatellites is particularly pronounced; these are repetitive poly(CA). poly(TG) DNA sequences spread in all eukaryotic genomes as tracts of up to 60 base pairs long. Many in vitro studies have shown that the structure of poly(CA). poly(TG) can vary markedly from the classical right handed DNA double helix and adopt diverse alternative conformations. Here we have studied the mechanism of formation and the structure of an alternative DNA structure, named Form X, which was observed previously by polyacrylamide gel electrophoresis of DNA fragments containing a tract of the CA microsatellite poly(CA). poly(TG) but had not yet been characterized. RESULTS: Formation of Form X was found to occur upon reassociation of the strands of a DNA fragment containing a tract of poly(CA). poly(TG), in a process strongly stimulated by the nuclear proteins HMG1 and HMG2. By inserting Form X into DNA minicircles, we show that the DNA strands do not run fully side by side but instead form a DNA knot. When present in a closed DNA molecule, Form X becomes resistant to heating to 100 degrees C and to alkaline pH. CONCLUSIONS: Our data strongly support a model of Form X consisting in a DNA loop at the base of which the two DNA duplexes cross, with one of the strands of one duplex passing between the strands of the other duplex, and reciprocally, to form a semicatenated DNA junction also called a DNA hemicatenane.
Binding, Competitive↗
Molecular characterization of the specificity of interactions of various neurotoxins on two distinct nicotinic acetylcholine receptors.
Snake curaremimetic toxins are currently classified as short-chain and long-chain toxins according to their size and their number of disulfide bonds. All these toxins bind with high affinity to muscular-type nicotinic acetylcholine receptor, whereas only long toxins recognize the alpha7 receptor with high affinity. On the basis of binding experiments with Torpedo or neuronal alpha7 receptors using wild-type and mutated neurotoxins, we characterized the molecular determinants involved in these different recognition processes. The functional sites by which long and short toxins interact with the muscular-type receptor include a common core of highly conserved residues and residues that are specific to each of toxin families. Furthermore, the functional sites through which alpha-cobratoxin, a long-chain toxin, interacts with muscular and alpha7 receptors share similarities but also marked differences. Our results reveal that the three-finger fold toxins have evolved toward various specificities by displaying distinct functional sites.
Animals↗
Y-specific microsatellite polymorphisms in a range of bovid species.
At least five dinucleotide (CA)n microsatellite repeat arrays have been assigned to the bovine Y-chromosome, with one marker (INRA124) shown to be polymorphic. We describe here the assessment of a panel of four Y-specific microsatellite markers for polymorphism in a range of cattle and related species. It was possible to amplify all the markers in the animals sampled and all showed variation. Three of the microsatellite loci (INRA124, INRA189 and BM861) displayed putative taurine- and zebu-specific alleles which can be useful indicators of male-mediated gene flow in hybrid populations. In the future these microsatellites, in combination with other Y-specific markers should provide a high-resolution Y haplotype system for evolutionary studies in both domesticated cattle and other related species.
Alleles↗
Phylogenetic analysis of the tribe Bovini using microsatellites.
The objective of the present study was to determine if the generally accepted phylogenetic relationships in the tribe Bovini correspond to a phylogenetic scheme derived from polymorphisms at 20 bovine microsatellite loci. This study comprises 17 representative populations: eight Bos taurus, two Bos indicus, one Poëphagus, one Bibos, one Bison, three Bubalus and one Syncerus. Phylogenetic analyses using (delta mu)2 and chord (DC) distances revealed substantial divergence among species. Neighbor-joining trees with both distance measures showed only minor differences. Bos taurus and Bos indicus grouped first, followed by Bos frontalis (Mithan) and Bos grunniens (Yak), Bison bison branched off next and Bubalus bubalis and Syncerus caffer emerged as the two most divergent species from the Bos clade. These findings would suggest that Bos, Poëphagus, and Bibos should be integrated into the Bos genus with each group classified as a subgenus. On the other hand, Bison, Bubalus and Syncerus should each be considered a separate genus. Direct estimates of the divergence times were calculated using the (delta mu)2 genetic distance. Bos taurus and Bos indicus were estimated to have diverged 0.31-0.82 MYA, Bos and Poëphagus: 0.57-1.53 MYA, Bos and Bibos: 0.57-1.52 MYA, Bos and Bison: 0.46-1.23 MYA, Bos and Bubalus: 1.85-4.93 MYA and Bos and Syncerus: 0.98-2.61 MYA.
Alleles↗
[Genetic investigations for control of hereditary diseases in dogs].
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Animals↗
Prevalence and infection risks of zoonotic enteropathogenic bacteria in Swiss cow-calf farms.
A longitudinal study was performed in 67 larger Swiss cow-calf farms from September 1996 through November 1997. The objectives of the study were to estimate prevalence and risk factors for colonization with potentially zoonotic enteropathogenic bacteria in younger calves and in calves at weaning age. The study included data from 395 calves with three to four fecal samples each. Fecal samples were analyzed for Campylobacter spp., verotoxin producing E. coli (VTEC), Yersinia spp. and Salmonella sp. Possible environmental and individual factors associated with colonization of these agents were examined. The calves were housed indoor during the first 3 months of life (winter 1996/1997). The prevalences within this time period were: C. coli 3.4%, C. fetus 15.5%, C. hyointestinalis 9.6%, C. jejuni 38.5%, VTEC 44.3% and Yersinia spp. 2%. At the end of the grazing season the prevalences at weaning (8-10 months of age) were: C. coli 1.7%, C. fetus 4.0%, C. hyointestinalis 25.9%, C. jejuni 13.3%, VTEC 38.2% and Yersinia spp. 0%. No salmonellae were present at any time of the study. The prevalences of C. jejuni and VTEC increased significantly within the first 3 months of life, whereas C. hyointestinalis decreased. None of the environmental factors such as housing or feeding had any consistent influences on colonization by the bacteria studied. VTEC, Campylobacter spp. and Yersinia spp. should probably be considered as normal inhabitants of the bovine intestinal tract. However, as they represent a source of gastrointestinal infections in humans, management factors limiting intestinal colonization of these bacteria should be considered in cow-calf operations.
Agglutination Tests↗
Identification of a pollen-specific sucrose transporter-like protein NtSUT3 from tobacco.
Pollen cells are symplasmically isolated during maturation and germination. Pollen therefore needs to take up nutrients via membrane carriers. Physiological measurements on pollen indicate sucrose transport in the pollen tube. A cDNA encoding a pollen-specific sucrose transporter-like protein NtSUT3 was isolated from a tobacco pollen cDNA library. NtSUT3 expression is detected only in pollen and is restricted to late pollen development, pollen germination and pollen tube growth. Altogether these data indicate that pollen is supplied not only with glucose, but also with sucrose through a specific sucrose transporter. The respective contribution of each transport pathway may change during pollen tube growth.
Amino Acid Sequence↗
Association of double-stranded DNA fragments into multistranded DNA structures.
We have previously observed that double-stranded DNA fragments containing a tract of the tandemly repeated sequence poly(CA). poly(TG) can associate in vitro to form stable complexes of low electrophoretic mobility, which are recognized with high specificity by proteins HMG1 and HMG2. The formation of such complexes has since been observed to depend on interactions of DNA with polypropylene surfaces, with the suggestion that the formation of low mobility complexes might be the result of strand dissociation followed by misaligned reassociation of the repetitive sequences. The data presented here show that at high ionic strength the interactions of DNA with polypropylene are sufficiently strong for DNA to remain bound to the polypropylene surface, which suggests that DNA might also be involved in interactions with hydrophobic molecules in vivo. Under such conditions, low-mobility complexes are found only in the material adsorbed to the polypropylene surface, and all DNA fragments are able to form low-mobility structures, whether or not they contain repetitive sequences. Preventing the separation of strands by ligating hairpin loop oligonucleotides at both ends of the fragments does not prevent the formation of low-mobility complexes. Our results suggest two different pathways for the formation of complexes. In the first, dissociation is followed by misaligned reassociation of repetitive sequences, yielding duplexes with single-stranded end regions that associate to form multimeric complexes. In the second, repetitive as well as nonrepetitive DNA molecules bound to polypropylene adopt a conformation with locally unwound regions, which allows interactions between neighboring duplexes adsorbed on the surface, resulting in the formation of low-mobility complexes.
DNA↗
Genetic diversity in Swiss goat breeds based on microsatellite analysis.
Genetic diversity in eight Swiss goat breeds was estimated using PCR amplification of 20 bovine microsatellites on 20-40 unrelated animals per breed. In addition, the Creole breed from the Caribbean and samples of Ibex and Bezoar goat were included. A total of 352 animals were tested. The bovine microsatellites chosen amplified well in goat. The average heterozygosity within population was higher in domestic goat (0.51-0.58) than in Ibex (0.17) and Bezoar goat (0.19). Twenty-seven per cent of the genetic diversity in the total population could be attributed to differences between the populations. However, with the exclusion of Ibex from the total population, this proportion dropped to 17%. Principal component analysis showed that all Swiss goat breeds are closely related, whereas the Creole breed, Ibex and Bezoar goat are clearly distinct from all eight Swiss breeds.
Animals↗
A new allelic variant in the bovine prion protein gene (PRNP) coding region.
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Alleles↗
Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog.
A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.
Animals↗
Differential expression of two skeletal muscle beta-tropomyosin mRNAs during Xenopus laevis development.
A cDNA clone for a Xenopus laevis skeletal muscle beta-tropomyosin (beta-TMad) isoform was isolated from an adult skeletal muscle cDNA library. Sequence analysis revealed that this clone corresponded to a second beta-tropomyosin mRNA distinct from the one that was previously characterized (beta-TMemb). The two skeletal beta-TM mRNAs originate from distinct genes and are differentially expressed during development. Beta-TMemb mRNA is expressed only in the somites of the early embryo while beta-TMad mRNA is expressed in pre-metamorphic tadpoles and adult skeletal muscles. We have isolated the promoter region of the beta-TMemb gene and shown that a DNA construct containing 2.9 kb of promoter region is properly expressed after injection in the embryo.
Animals↗
[General review of the value of hepatic MRI in the diagnosis and preoperative staging of liver metastasis from colon and rectum cancer].
Hepatic resection of secondary liver neoplasms is currently the only potentially curative therapy for patients with primary colorectal carcinoma. Long-term survival is closely related to stage, regardless of the number, size and distribution of liver lesions. Preoperative detection of liver metastases is crucial in patient staging and imaging techniques must be as accurate as possible to evaluate whether hepatic resection can be performed. Among the various strategies applied to the preoperative detection of liver metastases, CT with intra-arterial portography (CTAP) has been found to be the most sensitive technique. It is an invasive evaluation with a reported sensitivity ranging from 81 to 94% but with 6 to 15% of false-positive results. Recent studies demonstrate that MRI with superparamagnetic iron oxide has an equivalent sensitivity and specificity to CTAP. This paper reviews the technique of MRI, evaluates its sensitivity and specificity, and presents the advantages and draw backs of the technique.
Colonic Neoplasms↗