177,206 research outputs found
A novel spliced fusion of MLL with CT45A2 in a pediatric biphenotypic acute leukemia
No full textBackground: Abnormalities of 11q23 involving the MLL gene are found in approximately 10% of human leukemias. To date, nearly 100 different chromosome bands have been described in rearrangements involving 11q23 and 64 fusion genes have been cloned and characterized at the molecular level. In this work we present the identification of a novel MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia. Methods: Cytogenetics, fluorescence in situ hybridization (FISH), molecular studies (RT-PCR and LDI-PCR), and bioinformatic sequence analysis were used to characterize the CT45A2 gene as novel MLL fusion partner in pediatric acute leukemia. Results: Fluorescence in situ hybridization of the patient G-banded metaphases demonstrated a cryptic insertion of 11q23 in Xq26.3 involving the MLL gene. Breakpoint fusion analysis revealed that a DNA fragment of 653 kb from 11q23, containing MLL exons 1-9 in addition to 16 other 11q23 genes, was inserted into the upstream region of the CT45A2 gene located at Xq26.3. In addition, a deletion at Xq26.3 encompassing the 3' region of the DDX26B gene (exons 9-16) and the entire CT45A1 gene was identified. RNA analysis revealed the presence of a novel MLL-CT45A2 fusion transcript in which the first 9 exons of the MLL gene were fused in-frame to exon 2 of the CT45A2 gene, resulting in a spliced MLL fusion transcript with an intact open reading frame. The resulting chimeric transcript predicts a fusion protein where the N-terminus of MLL is fused to the entire open reading frame of CT45A2. Finally, we demonstrate that all breakpoint regions are rich in long repetitive motifs, namely LINE/L1 and SINE/Alu sequences, but all breakpoints were exclusively identified outside these repetitive DNA sequences. Conclusion: We have identified CT45A2 as a novel spliced MLL fusion partner in a pediatric patient with de novo biphenotypic acute leukemia, as a result of a cryptic insertion of 11q23 in Xq26.3. Since CT45A2 is the first Cancer/Testis antigen family gene found fused with MLL in acute leukemia, future studies addressing its biologic relevance for leukemogenesis are warranted
“LDI-PCR: IDENTIFICAZIONE DEI GENI DI FUSIONE CONOSCIUTI E SCONOSCIUTI DEL GENE UMANO MLL”
No full text
QTL effects for seed glucosinolate content in BC3 families of rapeseed (Brassica napus L.) segregating for single QTL only
No full textAppropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
STRUCTURE OF THE PROMOTER REGION OF THE GENE ENCODING CYTOCHROME-C-OXIDASE SUBUNIT-V IN DICTYOSTELIUM
No full textA cDNA for the nuclear-encoded subunit V of Dictyostelium discoideum cytochrome-c oxidase was used as a probe to screen a genomic library and isolate the complete gene. Primer-extension analysis revealed two transcription start sites located 32 and 39 nucleotides upstream of the translation initiation codon. The chloramphenicol acetyltransferase assay in transient and stable Dictyostelium transformants indicated that the 400-bp dT-rich segment 5' to the transcription start sites retained promoter activity. This region contains an octanucleotide sequence similar to the yeast HAP2/3/4 responsive elemen
A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3
No full textBackground: Severe von Willebrand disease (VWD) type 3 is caused by large deletions, insertions, small truncating mutations, splice site mutations and missense mutations of the VWF gene, respectively. Large deletions have been regarded as being a rare cause of VWD type 3. Complete gene deletions have only been identified in Italian and German patients to date. However, their extent and breakpoints have not been determined yet. Objectives: To identify the breakpoints of complete VWF deletions in patients with VWD type 3. Patients/methods: Five index patients with large deletions from two unrelated German and three Italian families were investigated by polymerase chain reaction (PCR) and primer walking. Haplotypes were composed of eight deletion flanking markers. Results: After initial characterization of a homozygous 253,246 bp deletion (Δ253 k) in a German patient, with the centromeric breakpoint located between CD9 and VWF and the telomeric breakpoint in intron 3 of TMEM16B, respectively, we identified the same Δ253 k in an additional two homozygous and two compound-heterozygous patients, and in their heterozygous parents. All patients share the same deletion-associated marker haplotype. The genomic structure of the breakpoint regions favors DNA double-strand breaks followed by non-homologous end-joining repair as an underlying molecular mechanism rather than a homologous recombination event. Conclusions: Our results suggest a single genetic origin of Δ253 k. Homozygosity for Δ253 k in non-consanguineous families from two different countries may indicate a higher incidence of large deletions in VWD type 3 than previously thought. The availability of a Δ253k-specific assay allows simple and rapid detection of even heterozygous patients and carriers
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