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A Wargelius

Publications and source records attributed to A Wargelius.

3 recordsLinked to original sources

RNA interference: mechanisms and applications.

RNA interference (RNAi) is a phenomenon induced by double-stranded RNA (dsRNA) in which gene expression is inhibited through specific degradation of mRNA. The mechanism involves conversion of dsRNA into short RNAs that direct ribonucleases to homologous mRNA targets. This process is related to normal defence against viruses and mobilisation of transposons. Treatment with dsRNA has become an important method for analysing gene functions in invertebrate organisms. RNAi has also been demonstrated in several vertebrate species but with lower efficiency. Development of procedures for in vivo production of dsRNA may provide efficient tools for tissue- and stage-specific gene targeting.

Animals↗

Fas and Fas ligand gene polymorphisms in primary Sjögren's syndrome.

OBJECTIVE: To screen for polymorphisms in the apoptosis regulating Fas and Fas ligand (FasL) genes in patients with primary Sjögren's syndrome (SS), and to explore associations with susceptibility to the disease. METHODS: Polymorphisms in Fas and FasL of 70 patients with primary SS and 72 controls were determined by polymerase chain reaction combined with the restriction enzyme fingerprinting single strand conformation polymorphism technique, verified by automatic sequencing and natural or amplification created restriction site tests. RESULTS: Polymorphisms were found in both Fas and FasL, but only some of the Fas polymorphisms were found in statistically significant differences between patients and controls. Patients displayed a higher frequency of the G/G genotype at position -671 than the controls, and the -671 G allele frequency for primary SS was increased compared to controls. A higher frequency of the C allele at position IVS2nt176 and IVS5nt82 was also found. Of note, the nucleotide variants in intron 2 and intron 5 were associated. CONCLUSION: We describe the positions and frequencies of several polymorphisms in the genes encoding Fas and FasL in patients with primary SS. None caused any amino acid change. Three Fas alleles, of which one is located in the promoter area, showed significant although modest differences between patients and controls.

Adult↗

Double-stranded RNA induces specific developmental defects in zebrafish embryos.

Treatment with double-stranded RNA (dsRNA) has been shown to interfere with the function of specific genes in various invertebrate species. However, it has not yet been reported that this technique can be applied to vertebrates as well. We have investigated whether dsRNA treatment will inhibit gene function in zebrafish embryos. By microinjecting dsRNA corresponding to three genetically characterised genes we produced embryonic defects that were similar to the known mutant phenotypes of these loci. The efficiency of inducing specific defects (20-30%) was about 10-fold higher than in experiments with antisense RNA. We also observed that the level of the endogenous mRNA in zebrafish embryos was substantially reduced throughout the embryo following dsRNA injection. However, the interference of gene function showed a strong dependence on the amount of dsRNA. These findings suggest that dsRNA-mediated interference will become an important tool for analysing the functional roles of genes in zebrafish and other vertebrates.

Animals↗