Analysis of Two Polymorphic Repeats IVS3 Poly A and IVS10 CA in Tunisian Cystic Fibrosis Patients: Case–Control Study

Russian Journal of Genetics - The aim of this study was to determine a possible association of IVS3 poly A and IVS10 CA microsatellites with CF in case–control Tunisian groups and to compare...     

Enhancing Bioinformatics and Genomics Courses: Building Capacity and Skills via Lab Meeting Activities

Reading, writing, publishing, and publicly presenting scientific works are vital for a young researcher's profile building and career development. Generally, the traditional educational curricula do not offer training possibilities to learn and practice how to prepare, write, and present scientific works. These are rather a part of lab meeting activities in research groups. The lack of such training is more critical in some developing countries because this adds to the rare opportunities to discuss and become involved in the exchanges on state of the art scientific literature. Here the authors relate their experience in introducing a weekly 1-day lab meeting in the framework of two previously organized 3-month courses on “Bioinformatics and Genome Analyses”. The main activities which are developed during these lab meetings include scientific literature follow up as well as preparing and presenting oral and written scientific reviews. These activities prove to be useful for a student's self-confidence building, for enhancing their active participation during the lectures and practical sessions, as well as for the positive impact on running the whole course program. Incorporation of such lab meeting activities in the course program significantly improves the capacity building of the participants, their analytical and critical reading of scientific literature, as well as communication skills. In this work it is shown how to proceed with the different steps involved in the implementation of lab meeting activities, and to recommend their regular institution in similar courses.     

Objective comparison of exon and intron sequences by means of 2-dimensional data analysis methods

Here we advocate the use of 2-dimensional data representation in the context of the informational approach of sequence analysis (Claverie & Bougueleret (1986) Nucleic Acids Research 14, 179-196) by applying these methods to the problem of intron/exon discrimination. Two main findings are reported: i) oligonucleotide patterns complementary to the Ul small nuclear RNA are specifically avoided in exon sequences, ii) vertebrate intron sequences, to the exclusion of other eukaryotic phyla, are characterized by a peculiar distribution of CpG containing patterns.     

Mutational spectrum of dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population

Dihydropyrimidine dehydrogenase enzyme (DPD) deficiency is a pharmacogenetic syndrome leading to severe side-effects in patients receiving therapies containing the anticancer drug 5-fluorouracil (5-FU). The aim of this population study is to evaluate gene variations in the coding region of the dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population. One hundred and six unrelated healthy Tunisian volunteers were genotyped by denaturing HPLC (DHPLC). Twelve variants in the coding region of the DPYD were detected. Allele frequencies of DPYD*5 (A1627G), DPYD*6 (G2194A), DPYD*9A (T85C), A496G, and G1218A were 12.7%, 7.1%, 13.7%, 5.7%, and 0.5%, respectively. The DPYD alleles DPYD*2A (IVS 14+1g>1), DPYD*3 (1897 del C) and DPYD*4 (G1601A) associated with DPD deficiency were absent from the examined subjects. We describe for the first time a new intronic polymorphism IVS 6-29 g>t, found in an allelic frequency of 4.7% in the Tunisian population. Comparing our data with that obtained in Caucasian, Egyptian, Japanese and African-American populations, we found that the Tunisian population resembles Egyptian and Caucasian populations with regard to their allelic frequencies of DPYD polymorphisms. This study describes for the first time the spectrum of DPYD sequence variations in the Tunisian population.     

A new feature: special issues

Editorial

A new feature: special issues     

Risk of vertical transmission of hepatitis B virus in Tunisia

The risk of vertical transmission of hepatitis B virus (HBV) varies with type of viral endemicity, degree of maternal infection and genomic characteristics of the virus. The aim of this study is to estimate this risk in Tunisia using serological and molecular methods to evaluate HBV replication, to determine viral genotypes and to detect presence of occult hepatitis in 2709 pregnant women. Serological markers were detected by ELISA methods, Genotype was determined by PCR-RFLP and occult hepatitis by nested-PCR. Four percent of women were positive for HBsAg; only 3% of them were also positive for HBeAg. Viral replication, over than 10(3) copies/ml, was detected in 61% of positive HBsAg patients. Three viral genotypes were detected: D (95%), B (3%) and A (3%). Occult hepatitis was detected in 4% of sera with "anti-HBc isolated" profile. In conclusion, the risk of vertical transmission of HBV exists in Tunisia. It increases by frequency of precore mutants, predominance of the genotype previously associated with high levels of replication and possibility of occult hepatitis B. These results show the importance of screening by serological HBV markers systematically during pregnancy with evaluation of viral replication in order to prevent vertical risk by efficient tools.     

Interactions between cardiac cells enhance cardiomyocyte hypertrophy and increase fibroblast proliferation

In cardiac hypertrophy, both excessive enlargement of cardiac myocytes (CMs) and progressive fibrosis are known to occur simultaneously. To investigate the nature of interactions between ventricular CMs and cardiac fibroblasts (CFs) in these conditions, we have established a "dedifferentiated model" of adult murine CMs in coculture with CFs. In such a model, which is recognized to study cardiac cell hypertrophy in vitro, dedifferentiated CMs in culture and in coculture were characterized by immunopositive staining to ANP (atrial natriuretic peptide) and beta-myosin heavy chain (beta-MHC). The results confirm that ANP secretion by CMs was significantly increased during the cultures. The increase size of cultured CMs was significantly higher in CM/CF cocultures than in CM cultures which was also observed when CMs were cultured with fibroblast conditioned medium (FCM). In addition, fibroblast proliferation studies showed that CMs favored fibroblast adhesion and/or growth at the beginning of the coculture and fibroblast proliferation throughout the time course of the coculture. Furthermore, a significant level of interleukin-6 (IL-6) production was detected by ELISA in CM/CF cocultures. A similar higher increase was observed when CMs were cultured in the presence of FCM. These results demonstrate that CFs enhance myocyte hypertrophy and that CMs regulate fibroblast adhesion and/or proliferation, suggesting a paracrine interaction between CMs and CFs which could involve IL-6.     

Genomic exploration of the hemiascomycetous yeasts: 20. Evolution of gene redundancy compared to Saccharomyces cerevisiae

We have evaluated the degree of gene redundancy in the nuclear genomes of 13 hemiascomycetous yeast species. Saccharomyces cerevisiae singletons and gene families appear generally conserved in these species as singletons and families of similar size, respectively. Variations of the number of homologues with respect to that expected affect from 7 to less than 24% of each genome. Since S. cerevisiae homologues represent the majority of the genes identified in the genomes studied, the overall degree of gene redundancy seems conserved across all species. This is best explained by a dynamic equilibrium resulting from numerous events of gene duplication and deletion rather than by a massive duplication event occurring in some lineages and not in others.     

Pervasiveness of Gene Conservation and Persistence of Duplicates in Cellular Genomes

In this work detailed statistics on ancestral gene duplication and gene conservation in completely sequenced cellular genomes are presented. Analysis of open reading frame (ORF) products having simultaneous matches in several distinct organisms showed a significant correlation between duplication and conservation. Systematic comparisons of predicted proteomes of 23 organisms (including 20 that have been completely sequenced), have allowed us to quantify the degree of ancestral duplication within each genome and the level of conservation between genomes, using threshold values calculated for individual organisms. Statistical analysis of various gene proportions revealed interesting trends in gene structure and evolution, such as that (a) more than one-quarter (25%–66%) of the predicted ORF products of the surveyed organisms are not unique, indicating a high level of ancestral duplications; (b) levels of exclusive conservation within Bacteria are higher than those within the eukaryal or archaeal domains; and (c) at least one-half (47–99%) of the total predicted ORF products in the surveyed genomes have one or several highly significant matches in another genome. Significant matches are based on simulations taking into account the mean size of ORF products and the composition of each target organism's proteome. The methodology we have developed ensures stability and comparability of our results as the number of completely sequenced genomes increases. Received: 4 May 1998 / Accepted: 28 September 1998