1,721,016 research outputs found
Related polypeptides are encoded by Drosophila F elements, I factors, and mammalian L1 sequences
No full textThe structural organization of Drosophila F elements closely resembles that of L1 sequences, a major family of repetitive DNA elements dispersed in the genome of all mammals. Members of both families are flanked by target-site duplications of different length, vary in size because of heterogeneity at one end, and invariably terminate at the other end in characteristic adenosine-rich stretches often preceded by polyadenylylation signals. The nucleotide sequence of Fw, an F element found in the white locus of wi+A flies, reveals a large open reading frame upstream of the 3' adenosine-rich terminus encoding a possible reverse transcriptase homologous to those potentially encoded by functional L1 units and Drosophila I factors. A cysteine-rich region within an interrupted frame located at the 5' terminus of Fw suggests that complete F elements might additionally encode a nucleic acid binding protein. The observation that F elements and I factors encode functionally related polypeptides, and the extensive similarity of their hypothetical reverse transcriptases to L1 open reading frames, favors the hypothesis that all these sequences are evolutionarily related and transpose upon the cDNA conversion of RNA intermediates
The genetic and molecular basis of epilepsy
No full textIn the past decade, studies of large families in which epilepsy has been inherited in an autosomal dominant fashion have revealed several mutated genes, most of which encode ion channel subunits. Despite these exciting findings, only a few families with similar phenotypes have mutations in these known genes. More frustrating has been the genetic research into idiopathic epilepsies with complex inheritance. Although these forms are more common than those with Mendelian inheritance, their unknown mode of inheritance, phenotypic heterogeneity and the uncertainty of the genetic overlap among syndrome subtypes have hampered gene mapping. New techniques of molecular analysis could help the dissection of genes for epilepsies with complex inheritance. Hopefully, in the near future, successful genetic studies will make possible the discovery of new and more-targeted anti-epileptic drugs
Genetic heterogeneity in Malattia Leventinese
No full textMalattia Leventinese (ML) is a dominant macular dystrophy characterized by drusen at the posterior pole. ML has been associated with a single mutation (R345W) in the EGF-containing. fibulin-like extracellular matrix protein 1 (EFEMP-1) gene, but also the EFEMP-2 gene, known to share genetic homology with EFEMP-1, is considered a candidate gene for this genetic disorder. We have characterized clinically and genetically seven members of a three-generation family affected by ML. Results showed that five family members were clinically affected but the DNA sequencing failed to reveal the typical R345W mutation. Furthermore, the linkage analysis to EFEMP-1 ( using polymorphic markers D2S337 and D2S2368) and to EFEMP-2 ( using D11S987 and D11S1314 markers) gave negative results. Therefore, our results suggest EFEMP-1 or EFEMP-2 genes cannot be excluded as being responsible for ML but other genes have to be considered in the pathogenesis of the disease
Multi-electrode array study of neuronal cultures expressing nicotinic β2-V287L subunits, linked to autosomal dominant nocturnal frontal lobe epilepsy. An in vitro model of spontaneous epilepsy
No full textA NOVEL BIPARTITE SPLICING ENHANCER MODULATES THE DIFFERENTIAL PROCESSING OF THE HUMAN FIBRONECTIN EDA EXON
No full textEDA is a facultative type III homology of human fibronectin encoded by an alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific distribution with their relative proportion varying during development, aging and oncogenic transformation. We have previously demonstrated that an 81 bp nucleotide sequence within the exon itself is essential for differential RNA processing. Fine mapping of cis acting elements within this region has been carried out to identify possible target sites for the modulation of alternative splicing. There are at least two short nucleotide sequences involved. Element A (GAAGAAGA) is a positive modulator for the recognition of the exon, its deletion results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a negative modulator for exon recognition, its deletion results in constitutive inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a novel feature of the mammalian exons
Locus for a novel syndromic form of neuronal intestinal pseudoobstruction maps to Xq28
No full textThe neuronal type of primary chronic idiopathic intestinal pseudoobstruction (CIIP) results from the developmental failure of enteric neurons to migrate or differentiate correctly. This leads to intestinal motility disorders, which are characterized by symptoms and signs of bowel obstruction in the absence of a mechanical obstacle. Most of these conditions are congenital, and among them some are inherited. One syndromic condition characterized by intestinal pseudoobstruction with morphological abnormalities of the argyrophil neurons in the myenteric plexus, associated with short small bowel, malrotation, and pyloric hypertrophy, has been previously described. We have studied a family affected by this disorder, in which the disease appeared to segregate as an X-linked recessive trait. In order to map the CIIP locus in this family, we performed linkage analysis in 26 family members by use of highly polymorphic microsatellite markers from the X chromosome. One of these markers, DXYS154, located in the distal part of Xq28, shows no recombination with a maximum lod score of 2.32. Multipoint analysis excluded linkage with markers spanning other regions of the X chromosome. Our results, integrated with the current genetic and physical map of Xq28, determine the order of loci as cen-DXS15-(CIIPX)-DXS1108/DXYS154-tel. This study establishes, for the first time, the mapping assignment of a neuropathic form of CIIP other than Hirschsprung disease
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