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PubMedDate not supplied

[The effect of continuous illumination and an inverse rhythm (light-darkness) on fibrinolysis].

The studies of chronobiology on biological phenomena revealed the existence of a human internal mechanism ("biological clock") which controls biological events according to each function of the body. Most of the programmed and genetically fixed rhythms can be changed and synchronized by external factors. Starting from these data and from our previous studies which emphasised an intradian rhythm of the proteolytic blood coagulation and fibrinolytic systems we observed the behaviour of the fibrinolytic system in modified environmental conditions (continuous illumination and inversed day-night rhythm). Our experiments were performed on 180 Wistar rats both male and female, submitted to continuous illumination and inversed rhythm for 1, 3 and 5 weeks. We studied plasma fibrinolytic activity (PFA) through euglobulin lysis time (ELT) at three different moments of the day: 8:30, 18:30 and 8:30 the next day. The study revealed intradian variations of PFA regardless of the type and time of submission. Thus: continuous illumination for 1, 3, 5 weeks determined a decrease of PFA (prolonged ELT) during the second part of the day, less important at 5 weeks. Inversed day-night rhythm for 1 and 3 weeks determined the same intradian behaviour of PFA but less important than continuous illumination. PFA variations in our experimental conditions suggest an alteration of its biological rhythm.

Animals↗
PubMed2005

Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23.

BACKGROUND: There is a high incidence of primary cutaneous amyloidosis (PCA) in South America, South-east Asia and Taiwan. To date, the aetiology of PCA remains unknown, but it is believed to be multifactorial. Although most cases are sporadic, some patients have a family history. Familial aggregation and different susceptibility to PCA among ethnic groups suggest that genetic factors may play an important role in its pathogenesis. However, no genetic loci for familial PCA (FPCA) have been identified so far. OBJECTIVES: In order to identify the susceptibility gene of FPCA, we took a candidate gene approach and performed linkage analysis on chromosome 1q21.3-24.2, including the 1q23.2 region where the gene encoding serum amyloid P component (APCS) is located. PATIENTS AND METHODS: Nine FPCA families including 29 individuals affected with PCA were recruited for this linkage study. Initially, 11 highly polymorphic microsatellite markers spanning the region from 1q21.3 to 1q24.2 were genotyped and revealed a suggestive linkage region. This region was further fine-mapped with seven additional markers. We also re-sequenced the 2.5-kb genomic region of the APCS gene in 29 affected and 42 control individuals. Two-point and multipoint linkage analyses were performed using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: Both two-point and multipoint linkage analysis for all 11 markers generated negative or small positive total lod scores for all nine families. However, when we considered only three families, a maximum two-point total lod score of 2.09 was obtained for the marker D1S2844 at theta = 0.01. A plateau of multipoint total lod score between D1S2768 and D1S2878 with a maximum of 2.48 at the marker D1S2844 was observed. A maximum NPL score of 3.11 (P = 0.008) was also obtained for the marker D1S2878. However, re-sequencing of the APCS gene identified no functional mutation. CONCLUSIONS: Both parametric and nonparametric linkage evidence suggested that a possible susceptibility locus for a subset of FPCA might exist on chromosome 1q23. This is the first report demonstrating suggestive evidence of linkage of FPCA to a locus in this candidate region. No functional sequence variations of the APCS gene were found to be associated with this disease among the study families. Our data imply the existence of at least one additional locus responsible for FPCA in these families, confirming genetic heterogeneity of this skin disorder.

Adolescent↗
PubMed2003

Identification of quantitative trait loci for production traits in commercial pig populations.

The aim of this study was to investigate methods for detecting QTL in outbred commercial pig populations. Several QTL for back fat and growth rate, previously detected in experimental resource populations, were examined for segregation in 10 different populations. Two hundred trait-by-population-by-chromosome tests were performed, resulting in 20 tests being significant at the 5% level. In addition, 53 QTL tests for 11 meat quality traits were declared significant, using a subset of the populations. These results show that a considerable amount of phenotypic variance observed in these populations can be explained by major alleles segregating at several of the loci described. Thus, despite a relatively strong selection pressure for growth and back fat traits in these populations, these alleles have not yet reached fixation. The approaches used here demonstrate that it is possible to verify segregation of QTL in commercial populations by limited genotyping of a selection of informative animals. Such verified QTL may be directly exploited in marker-assisted selection (MAS) programs in commercial populations and their molecular basis may be revealed by positional candidate cloning.

Adipose Tissue↗
PubMed1999

Genetic polymorphism of falciparum malaria vaccine candidate antigen genes among field isolates in India.

The present study was designed to investigate the genetic diversity of Plasmodium falciparum among field isolates from India. A total of 71 clinical isolates were analyzed by the polymerase chain reaction (PCR) for the amplification of repeat regions of malaria vaccine candidate antigen genes, i.e., merozoite surface antigen-1 (MSA-1), MSA-2, and circumsporozoite protein (CSP). All three genes showed variation; MSA-2 has the maximum number of 10 variant forms while MSA-1 and CSP had 8 and 6 variants, respectively. Some variant forms were more common than others among the clinical isolates. There were mixed alleles for each gene in several (27 of 71) cases. The MSA-2 gene showed the maximum number of cases with mixed alleles (22 of 65 [33.85%]) compared with MSA-1 (10 of 68 [14.7%]) and CSP (10 of 65 [15.38%]). Fifty-five (88.7%) of 62 clinical isolates of P. falciparum showed a different genotype. The malaria hyperendemic region (Orissa) not only showed the maximum number of variant forms of each gene but also the maximum number of cases with mixed alleles compared with the non-hyperendemic regions (Madhya Pradesh and Rajasthan). The presence of such large numbers of P. falciparum strains in India should be taken into account in future malaria vaccine programs.

Alleles↗
PubMed2007

Protein kinase C-beta 1 gene variants are not associated with autism in the Irish population.

Some evidences indicate that protein kinase C-beta 1 (PRKCB1) gene may be a predisposition locus of autism. A recent study reported evidence of association between autism and two haplotypes made up of six noncoding single nucleotide polymorphisms in the PRKCB1. To attempt replication of their findings, we examined the same six single nucleotide polymorphisms of PRKCB1 in 171 Irish autism trios. The haploview program was used to calculate D' as a measure of linkage disequilibrium. The transmission disequilibrium test for single nucleotide polymorphism markers and haplotypes was carried out using the TDTPHASE and PDTPHASE from the UNPHASED version 2.404 programs. Transmission disequilibrium test analysis showed no evidence of association for any of the six single nucleotide polymorphisms at the PRKCB1 that we studied, or any of their haplotypes. Our data do not support the finding that the PRKCB1 gene variants contribute risk for the development of autism.

Autistic Disorder↗
PubMed2004

Clinical and molecular aspects of haemoglobinopathies in Tunisia.

BACKGROUND: For the last two decades, studies on the population genetics of Tunisians have focused on variations of protein and genetic markers. Results confirmed the genetic heterogeneity of Tunisians caused by the admixtures with migratory human groups arriving mainly from Africa, Europe, and Asia. These studies also allowed the screening of rare mutants and many haemoglobin variants. METHODS: The present study delineates the incidence of the different haemoglobinopathies in Tunisia. Previously collected data and results obtained from epidemiological and clinical studies of 1238 blood donors and 276 patients were compared. The chromosomal backgrounds of different haemoglobinopathies were explored by molecular techniques (denaturing gradient gel electrophoresis (DGGE), amplification refractory mutation system (ARMS) polymerase chain reaction (PCR), and sequencing). RESULTS: This study indicates that appropriate DNA methodologies required for a nationwide preventive program in Tunisia are available and that prenatal diagnosis is feasible. Additionally, analysis of sequence polymorphisms allowed a better understanding of the gene recombination events and their application for tracing back the origin and the diffusion of the mutations. CONCLUSIONS: Molecular analysis techniques such as DGGE and ARMS PCR are socially and economically the most suitable techniques to be used in Tunisia for the detection and the identification of haemoglobin abnormalities. At present, their use is essential to conduct a clear and efficient screening program.

Anemia, Sickle Cell↗
PubMed1988

Impact on radiogenic cancer risk of persons exhibiting abnormal sensitivity to ionizing radiation.

Human genotypes are known "that confer both increased susceptibility or resistance to DNA damage and increased cancer risk after exposure to carcinogenic agents, including ionizing radiation" (NAS 1980). The existence of sensitive subgroups at elevated risk, if they are of appreciable size, could have significant impact on the actual distribution of risk. The radiosensitive disorder ataxia-telangiectasia (A-T) serves as a good example: the significant "at risk" group, A-T heterozygotes, is estimated to comprise between 0.5% and 5% of the total population, and has a twofold elevated lifetime risk of fatal neoplasia. Other genetic syndromes that manifest abnormal radiosensitivity are also known, but no estimates are available for the population frequency of all such phenotypes, or for their overall degree of increased risk. As the first part of a program addressing these questions, we have developed a rapid and inexpensive assay for screening members of the general population for abnormal radiosensitivity; such persons would be regarded as at presumptive elevated risk of radiogenic cancer. Our method utilizes lymphoblastoid cell lines and chronic as opposed to acute gamma-ray exposure to amplify the difference between normal and somewhat sensitive strains. A simple "grow-back" assay assesses the survival response. Information on the extent of natural variation in inherited susceptibility to radiogenic cancers could be most useful for radiation protection in the future.

Cell Line↗
PubMed1993

Detection of sequence variations in the human insulin-receptor gene by parallel denaturing gradient gel electrophoresis.

We developed a parallel denaturing gradient gel electrophoresis (DGGE) protocol to maximize the detection of nucleotide variants in the DNA sequence coding for the mature insulin receptor and in splice site junctions. The melting behaviours of exons 2 to 22 and flanking intronic sequences were computer-simulated using two programs, MELT87 and SQHTX. The data obtained from computer analysis were used to select primers for amplification by polymerase chain reaction and optimal electrophoretic conditions. The ability of this protocol to detect nucleotide changes at the insulin-receptor locus was assessed by studying amplified DNA of a patient with leprechaunism whose insulin-receptor mutations were known and by screening the insulin-receptor gene for polymorphisms in a population of unrelated caucasian individuals. Our results demonstrate that this DGGE protocol is sensitive since it detected (1) sequence variants reported to be undetectable by means of parallel DGGE, (2) previously characterized insulin-receptor nucleotide variants, and (3) unreported polymorphisms at the insulin-receptor locus of caucasian individuals. It is also simple as perpendicular denaturing gradient gels are not required. Application of this protocol will facilitate the search for molecular defects underlying the pathogenesis of insulin resistance observed in genetic syndromes of severe insulin resistance as well as in other metabolic disorders. In addition, its ability to detect several regions of the insulin-receptor gene displaying a number of common polymorphic sites and being multiallelic will contribute to linkage studies in families with diabetic and/or insulin-resistant subjects.

Base Sequence↗
PubMed1995

A FORTRAN program to simulate the evolution of genetic variability in a small population.

This paper presents a FORTRAN-77 program that performs Monte Carlo simulation of the evolution of genetic structure in a small population under selection. The aim is to study the possibility of foreseeing a response plateau in a theoretical population, depending on population size and management, and to apply this to small populations actually selected, to predict a possible exhaustion of genetic variability. A set of subroutines describing the different steps in a selection cycle (birth, expression of phenotypic value, genetic evaluation, selection, reproduction, death) is available and the user can choose the sequence of subroutines, the characteristics of individuals submitted to each step, and also build more personal subroutines if necessary. The program is based on the generation of exact genotypes and their transmission from parents to offspring, through simulation of meiosis and pairing of gametes. Parameters concerning the genome, the initial structure of the population and its management are required. The genetic mean and variance of the population for each new cycle of selection are given as outputs. Examples of applications are given and discussed.

Algorithms↗
PubMed2002

Temporal and distinct TGFbeta ligand requirements during mouse and avian endocardial cushion morphogenesis.

The formation of endocardial cushions in the atrioventricular (AV) canal of the rudimentary heart requires epithelial-to-mesenchymal cell transformation (EMT). This is a complex developmental process regulated by multiple extracellular signals and transduction pathways. A collagen gel assay, long used to examine endocardial cushion development in avian models, is now being employed to investigate genetically engineered mouse models with abnormal heart morphogenesis. In this study, we determine interspecies variations for avian and mouse cultured endocardial cushion explants. Considering these observed morphologic differences, we also define the temporal requirements for TGFbeta2 and TGFbeta3 during mouse endocardial cushion morphogenesis. TGFbeta2 and TGFbeta3 blocking antibodies inhibit endothelial cell activation and transformation, respectively, in avian explants. In contrast, neutralizing TGFbeta2 inhibits cell transformation in the mouse, while TGFbeta3 antibodies have no effect on activation or transformation events. This functional requirement for TGFbeta2 is concomitant with expression of TGFbeta2, but not TGFbeta3, within mouse endocardial cushions at a time coincident with transformation. Thus, both TGFbeta2 and TGFbeta3 appear necessary for the full morphogenetic program of EMT in the chick, but only TGFbeta2 is expressed and obligatory for mammalian endocardial cushion cell transformation.

Actins↗
PubMed2003

Two novel somatic mutations in the human interleukin 6 promoter region in a patient with sporadic breast cancer.

Two new single nucleotide mutations were observed within the promoter region of human interleukin-6 gene (IL-6) in the tumour sample of a patient with sporadic breast cancer, which was a somatic change. Both mutations, one at -125 (C > G) and the other at position -173 (G > T) from the translation start site, were transversions observed at new positions, not reported earlier. In addition to these two novel mutations in this patient, a known somatic polymorphism was also observed at position -174 (G > C) (from the transcription initiation site, redesignated as -236 from the translational initiation site as per the HUGO nomenclature). Further, a preliminary comparative analysis of the studied promoter region by the 'ConsInspector 3.0' program, where the mutated sequence (AF362378) was compared with the sequence existing in the database (Y00081), depicted the presence of the variations in putative binding sites for transcription factors such as glucocorticoid response element (GRE) and nuclear factor kappa-B (NFkappa-B), which could lead to differential expression of this gene.

Base Sequence↗
PubMed2004

Differential basal expression of genes associated with stress response, damage control, and DNA repair among mouse tissues.

Efficient recognition and repair of DNA damage is essential for maintaining genomic integrity. Tissues and cell types within tissues appear to vary in both DNA damage susceptibilities and cancer incidences, yet the molecular mechanisms underlying these differences are not well understood. The purpose of this study was to characterize the baseline transcription profiles of selected genes involved in DNA damage recognition and repair processes among several tissues of healthy adult B6C3F1 mice (testis, brain, liver, spleen and heart), which are routinely used by the National Toxicology Program (NTP) to conduct long-term chemical carcinogenicity studies. Stress response, damage control and DNA repair-associated genes were differentially expressed among the tissues examined. Overall, stress response genes exhibited the greatest variation among tissues with the highest expression in liver and heart while DNA repair genes exhibited the least variation. Damage control genes associated with cell cycle regulation and DNA repair genes generally had the highest expression in testis. The expression levels of several genes were rank correlated with the spontaneous cancer incidences among these tissues. Variations in basal expression of DNA damage recognition and repair-associated genes among healthy tissues may contribute to their differential response to genotoxic agents and susceptibility to genetic disease.

Animals↗
PubMed2002

RAPD analysis of herbicide-resistant Brasilian rice lines produced via mutagenesis.

Over the last two decades, mutational techniques have become one of the most important tools available to progressive rice- breeding programs. In a mutation-breeding program initiated in 1999 at the Instituto Agronômico of Campinas, SP, Brazil, a rice line, IAC103, was selected for mutational studies with gamma radiation and ethyl methyl sulfonate mutagenesis, with the aim of developing a herbicide-resistant crop. After mutagenesis, surviving plants were exposed to glufosinate to check for herbicide resistance, which was examined up to the second generation. A detailed RAPD analysis was made of the resistant plants. Eighty Operon technology primers were tested and 10 were selected for a detailed study of RAPD markers that could tag herbicide resistance genes. Resistant and susceptible lines produced variation in the RAPD patterns and certain bands were found only in certain lines. These results suggest genetic ligation that will be confirmed through a genetic segregation study.

Aminobutyrates↗
PubMedDate not supplied

[The maternal-fetal system as an object for the study of mechanisms of the physiologic effect of weightlessness].

The place of embryological investigations in the program of mammalian experiments onboard the Cosmos biosatellites is discussed. The mother-fetus system is viewed as a specific loading test for studying the reserve potentials of the mammalian body in microgravity. It has been demonstrated that mammalians (Wistar rats) flown during the third term of their pregnancy can maintain homeostasis of the developing fetus within the limits that provide the normal development of physiological functions. Significant individual variations in animal responses to microgravity have also been found.

Adaptation, Physiological↗
PubMed2005

Molecular changes in the maize composite EPS12 during selection for resistance to pink stem borer.

The pink stem borer (Sesamia nonagrioides Lefèvbre) is the most important pest of maize (Zea mays L.) throughout the Mediterranean area. The maize composite EPS12 has been chosen as the base population for a breeding program based on its resistance to pink stem borer, with the main selection criterion being resistance to stem tunneling. Yield was taken as a secondary selection criterion to avoid any unwanted negatively correlated response on this character. The aims of investigation were: (1) to monitor the effects of selection for resistance to pink stem borer on allele frequency at 70 simple sequence repeat (SSR) markers and their impact on the genetic structure of EPS12 and (2) to identify loci at which allelic frequencies changed significantly due to directional selection. Genetic diversity was reduced during the selection process (as expected since random genetic drift as well as selection could reduce genetic variability), but not significantly so. Although the loss of genetic variation was generally consistent with that expected in a model in which random genetic drift acts alone on neutral alleles, the changes observed in the frequency of five alleles were significantly greater than expected. Further, the linear trend of the departure from the random genetic drift model was significant for some allelic versions of two SSR markers, umc1329 and phi076; directional selection was therefore acting on these loci. The significant effect of directional selection on those markers suggests the presence of quantitative trait loci (QTLs) for tunnel length and/or for yield under artificial infestation with Sesamia nonagrioides on the long arm of chromosome 4.

Animals↗
PubMed2006

Local genetic diversity of sorghum in a village in northern Cameroon: structure and dynamics of landraces.

We present the first study of patterns of genetic diversity of sorghum landraces at the local scale. Understanding landrace diversity aids in deciphering evolutionary forces under domestication, and has applications in the conservation of genetic resources and their use in breeding programs. Duupa farmers in a village in Northern Cameroon distinguished 59 named sorghum taxa, representing 46 landraces. In each field, seeds are sown as a mixture of landraces (mean of 12 landraces per field), giving the potential for extensive gene flow. What level of genetic diversity underlies the great morphological diversity observed among landraces? Given the potential for gene flow, how well defined genetically is each landrace? To answer these questions, we recorded spatial patterns of planting and farmers' perceptions of landraces, and characterized 21 landraces using SSR markers. Analysis using distance and clustering methods grouped the 21 landraces studied into four clusters. These clusters correspond to functionally and ecologically distinct groups of landraces. Within-landrace genetic variation accounted for 30% of total variation. The average F(is) over landraces was 0.68, suggesting high inbreeding within landraces. Differentiation among landraces was substantial and significant (F(st) = 0.36). Historical factors, variation in breeding systems, and farmers' practices all affected patterns of genetic variation. Farmers' practices are key to the maintenance, despite gene flow, of landraces with different combinations of agronomically and ecologically pertinent traits. They must be taken into account in strategies of conservation and use of genetic resources.

Cameroon↗
PubMed2002

Including measured genotypes in statistical models to study the interplay of multiple factors affecting complex traits.

The etiology of complex traits may perhaps best be conceptualized by an interplay of multiple factors that mediate the influence of the genes on the eventual outcome. The possibilities of studying aspects of this interplay using existing methods are generally limited. We therefore propose a model with observed and latent variables that does not impose restrictions on the number of variables or the direction of their causal relations and provides a general approach for fitting structural equation models to empirical data. The model is very flexible and (1) allows for genetic effects on the means, variances, and relations between variables, (2) can control for stratification effects on all these components, (3) can be fitted in nuclear families of any size, (4) is estimated using an interpretable parameterization, and (5) can incorporate di- and multi-allelic loci, marker haplotypes, multiple loci simultaneously, and parental genotypes. We indicate how the model can be estimated with the Mx software (Neale et al., 1999) and have written a program to enable geneticists who are not acquainted with Mx to fit their own submodels in a simple and efficient way. A simulation study showed that the model yielded correct Type I errors, unbiased parameter estimates, and satisfactory power to discriminate between alternative models. An example is also given that illustrates how the model could be applied to real data.

Gene Frequency↗
PubMed1992

Signature pattern analysis: a method for assessing viral sequence relatedness.

Signature pattern analysis identifies particular sites in amino acid or nucleic acid alignments of variable sequences that are distinctly representative of a query set of sequences relative to a background set. We explore the merits of using signature patterns for analysis of HIV-1 (human immunodeficiency virus type 1) sequences in cases of epidemiological linkage and potential superinfection. For these purposes, query sets are viral sequences that are all derived from one HIV-1 infected individual, hence the signature pattern is the array of sites that are characteristic of the range of viral variants obtained from that person. Once a signature pattern has been objectively defined, it can be used to examine other viral sequences from other individuals for evidence of genetic relatedness. A computer program to facilitate this analysis, VESPA, is described and applied to sequence data gathered during the investigation of HIV-1 transmission in a dental practice. The implications of signature polymorphisms seen within an infected individual, and shared polymorphisms between linked individuals, are also considered. VESPA may also be applied to the molecular analysis of biological phenotypes.

Amino Acid Sequence↗