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Angela M Vianna-Morgante

Publications and source records attributed to Angela M Vianna-Morgante.

12 recordsLinked to original sources
PubMed2006

UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome.

We report a mutation of UBE2A/HR6A, which encodes a ubiquitin-conjugating enzyme (E2), a member of the ubiquitin proteasome pathway, as the cause of a novel X-linked mental retardation (XLMR) syndrome that affects three males in a two-generation family. A single-nucleotide substitution, c.382C-->T in UBE2A, led to a premature UAG stop codon (Q128X). As a consequence, the predicted polypeptide lacks the 25 C-terminal amino acid residues. The importance of this terminal sequence for UBE2 function is inferred by its conservation in vertebrates and in Drosophila. UBE2A mutations do not appear to significantly contribute to XLMR, since no UBE2A mutations were identified in 15 families with nonsyndromic and 4 families with syndromic idiopathic XLMR previously mapped to intervals encompassing this gene. This is the first description of a mutation in a ubiquitin-conjugating enzyme gene as the cause of a human disease.

Adult↗
PubMed2005

An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines a new locus (FGS5) for FG syndrome.

FG syndrome is an X-linked multiple congenital anomalies (MCA) syndrome. It has been mapped to four distinct loci FGS1-4, through linkage analysis (Xq13, Xp22.3, and Xp11.4-p11.3) and based on the breakpoints of an X chromosome inversion (Xq11:Xq28), but so far no gene has been identified. We describe a boy with FG syndrome who has an inherited duplication at band Xq22.3 detected by comparative genomic hybridization microarray (Array-CGH). These duplication maps outside all four loci described so far for FG syndrome, representing therefore a new locus, which we propose to be called FGS5. MID2, a gene closely related to MID1, which is known to be mutated in Opitz G/BBB syndrome, maps within the duplicated segment of our patient. Since FG and Opitz G/BBB syndromes share many manifestations we considered MID2 a candidate gene for FG syndrome. We also discuss the involvement of other potential genes within the duplicated segment and its relationship with clinical symptoms of our patient, as well as the laboratory abnormalities found in his mother, a carrier of the duplication.

Abnormalities, Multiple↗
PubMed2004

Crotamine is a novel cell-penetrating protein from the venom of rattlesnake Crotalus durissus terrificus.

Herein we report that crotamine, a small lysine- and cysteine-rich protein from the venom of the South American rattlesnake, can rapidly penetrate into different cell types and mouse blastocysts in vitro. In vivo crotamine strongly labels cells from mouse bone marrow and spleen and from peritoneal liquid, as shown by fluorescent confocal laser-scanning microscopy. Nuclear localization of crotamine was observed in both fixed and unfixed cells. In the cytoplasm, crotamine specifically associates with centrosomes and thus allows us to follow the process of centriole duplication and separation. In the nucleus, it binds to the chromosomes at S/G2 phase, when centrioles start dividing. Moreover, crotamine appears as a marker of actively proliferating cells, as shown by 5-BrdU cell-proliferation assay. Crotamine in the micromolar range proved nontoxic to any of the cell cultures tested and did not affect the pluripotency of ES cells or the development of mouse embryos.

Animals↗
PubMed2003

Developmental changes in the ploidy of mouse implanting trophoblast cells in vitro.

Shortly after the onset of implantation, polar mouse trophoblast cells proliferate and give rise to the ectoplacental cone, constituted by two distinct cell populations: undifferentiated, diploid cells and giant cells. Giant cells characteristically exhibit exaggerated dimensions and polyploid nuclei. In this study, we employ ectoplacental cones as a dynamic source of trophoblast giant cells to analyze cell proliferation, cell death, and ploidy under in vitro conditions. Our results show that DNA synthesis and the increase in the cell number are relevant only during the first 24 h of culture. Subsequently, DNA synthesis still occurs, mainly in the giant cell compartment, while the number of cells gradually decreases. Cell death by injury and apoptosis was also observed in the non-giant cell compartment of the ectoplacental cone. These findings suggest that the first 24 h of culture are crucial to the mitotic activity of the ectoplacental cone cells that gradually ceases, favoring the endoreduplication process. The DNA synthesis index during the subsequent experimental intervals emphasizes accumulation of DNA for the polyploidization. There was clear correlation between DNA content and nuclear dimension. The ploidy values for the trophoblast giant cells varied from 2C up to 368C in the giant cells, but were not as expressive as those known from in vivo conditions, probably due to the absence of regulatory factors specific to the embryonic-maternal interface. In situ hybridization and histochemistry for the nucleolus-organizing region showed that trophoblast nuclei have only two marker signals, indicative of a typical polytenic process. This present study elucidates important aspects of trophoblast behavior and provides new information on trophoblast physiology in vivo and in vitro.

Animals↗
PubMed2003

Disclosing the mechanisms of origin of de novo short-arm duplications of chromosome 9.

Three de novo short-arm duplications of chromosome 9 were investigated by fluorescence in situ hybridization (FISH) and genotyping of microsatellite loci with the aim of disclosing their mechanisms of origin. Two of these duplications were identified as direct and one as an inverted duplication, and they comprised nearly the entire 9p. In the two dirdup(9p), the distal breakpoints were mapped to subtelomeric sequences, whereas the proximal break boundaries were defined by pericentromeric sequences. The maternal origin of both duplications was demonstrated, and the presence of three different alleles in distal loci indicated that these rearrangements must have occurred prezygotically. In the invdup(9p), the proximal breakpoint was mapped at the alphoid sequences, which were partially duplicated on the tip of the rearranged 9p; subtelomeric and telomeric sequences were not detected, allowing the distal breakpoint to be mapped proximally to subtelomeric sequences. Genotyping of microsatellite loci allowed us to conclude that this invdup(9p) chromosome had a paternal origin. Homozygosity throughout the duplicated segment pointed to its probable postzygotic formation. Chromatid rearrangements appeared to have originated these 9p duplications, involving pericentromeric and subtelomeric sequences. These rearrangements might have been the result of recombination events between homologous repeats in these segments.

Adolescent↗
PubMed2003

Structure and chromosomal localization of the gene for crotamine, a toxin from the South American rattlesnake, Crotalus durissus terrificus.

Crotamine is a 42 amino acid-long basic polypeptide, one of the major components of the South American rattlesnake, Crotalus durissus terrificus, venom. The mRNA has about 340 nucleotides and codifies a pre-crotamine, including the signal peptide, the mature crotamine, and a final lysine. In this report, we describe the crotamine gene with 1.8 kb organized into three exons separated by a long phase-1 (900 bp) and a short phase-2 (140 bp) introns. Exon 1 includes the 5'-untranslated region and codifies the first 19 amino acids of the signal peptide. Exon 2 codifies 42 amino acids, three belonging to the signal peptide and 39 to the mature crotamine. Exon 3 codifies the last three amino acids of the mature toxin and the terminal lysine. The crotamine gene was mapped by in situ hybridization to the end of the long arm of chromosome 2, the intensity of signals differing between the two homologues. This may reflect a difference in gene copy numbers between chromosomes, a possible explanation for the variable amounts of crotamine found in the venom.

Animals↗
PubMed2003

Conservation of chromosomal location of nucleolus organizer in American marsupials (Didelphidae).

The distribution and expression of nucleolus organizer regions (NORs) were analyzed in seven species of marsupials representative of the three karyotypes (2n = 14, 18 and 22) found in the American family Didelphidae. Analyses comprised silver-staining of NORs and fluorescence in situ hybridization with an rDNA probe. In addition to confirming the variability in number and distribution of NORs in Didelphidae, we demonstrated the conserved location of NORs on one autosome pair in the three karyotypes. In Monodelphis domestica (2n = 18), the NOR on the X chromosome was not inactivated in females.

Animals↗
PubMed2002

Delimitation of duplicated segments and identification of their parental origin in two partial chromosome 3p duplications.

Two chromosome 3 short arm duplications identified through G-banding were further investigated using fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) of microsatellite markers, aiming at mapping breakpoints and disclosing mechanisms of origin of these chromosome aberrations. Patient 1 was found to be a mosaic: a 3p12 --> 3p21 duplication was observed in most of his cells, and a normal cell line occurred with a frequency of about 3% in blood. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the short-arm duplication. Using FISH of short-arm sequences, the YAC 961_h_3 was shown to contain the proximal breakpoint (3p12.1 or 3p12.2), and the distal breakpoint was located between the YACs 729_c_3 and 806_h_2, which are adjacent in the WC 3.10 contig (3p21.1). In Patient 2, G-banding indicated a 3p21 --> 3p24 duplication, without mosaicism. In situ hybridization of chromosome 3 short- and long-arm libraries confirmed the duplication of short-arm sequences. FISH of chromosome 3 sequences showed that the YAC 749_a_7 spanned the proximal breakpoint (3p21.33). The distal breakpoint mapped to the interval between YACs 932_b_6 (3p24.3) and 909_b_6 (3p25). In both cases, microsatellite genotyping pointed to a rearrangement between paternal sister chromatids.

Adolescent↗
PubMed2002

Distribution of CGG repeats and FRAXAC1/DXS548 alleles in South American populations.

In order to assess the molecular variability related to fragile X (FMR1 locus), we investigated the distribution of CGG repeats and DXS548/FRAXAC1 haplotypes in normal South American populations of different ethnic backgrounds. Special attention was given to Amerindian Wai-Wai (Northern Brazil) and Ache (Paraguay), as well as to Brazilian isolated communities of African ancestry, the remnants of quilombos. Comparison of samples from quilombos, Amerindians, and the ethnically mixed, but mainly European-derived population of São Paulo revealed that the 30-copy allele of the fragile X gene is the most frequent in all groups. A second peak at 20 repeats was present in the population of São Paulo only, confirming this as a European peculiarity. The distribution of DXS548 and FRAXAC1 alleles led to a high expected heterozygosity in African Brazilians, followed by that observed in the population of São Paulo. Amerindians showed the lowest diversity in CGG repeats and DXS548/FRAXAC1 haplotypes. Some rare alleles, for example, the 148-bp (FRAXAC1) or 200-bp (DXS548) variants, which seem to be almost absent in Europe, occurred in higher frequencies among African Brazilians. This suggests a general trend for higher genetic diversity among Africans; these rarer alleles could be African in origin and would have been lost or possibly were not present in the groups that gave rise to the Europeans.

Alleles↗