Molecular Cytogenetics
1755-8166
Cơ quản chủ quản: BMC , BioMed Central Ltd.
Lĩnh vực:
Molecular MedicineBiochemistry (medical)Genetics (clinical)GeneticsBiochemistryMolecular Biology
Các bài báo tiêu biểu
Chromoanagenesis: a piece of the macroevolution scenario Abstract Over the last decade, new types of massive and complex chromosomal rearrangements based on the chaotic shattering and restructuring of chromosomes have been identified in cancer cells as well as in patients with congenital diseases and healthy individuals. These unanticipated phenomena are named chromothripsis, chromoanasynthesis and chromoplexy, and are grouped under the term of chromoanagenesis. As mechanisms for rapid and profound genome modifications in germlines and early development, these processes can be regarded as credible pathways for genomic evolution and speciation process. Their discovery confirms the importance of genome-centric investigations to fully understand organismal evolution. Because they oppose the model of progressive acquisition of driver mutations or rearrangements, these phenomena conceptually give support to the concept of macroevolution, known through the models of “Hopeful Monsters” and the “Punctuated Equilibrium”. In this review, we summarize mechanisms underlying chromoanagenesis processes and we show that numerous cases of chromosomal speciation and short-term adaptation could be correlated to chromoanagenesis-related mechanisms. In the frame of a modern and integrative analysis of eukaryote evolutionary processes, it seems important to consider the unexpected chromoanagenesis phenomena.
- 2020
Determining parental origin of embryo aneuploidy: analysis of genetic error observed in 305 embryos derived from anonymous donor oocyte IVF cycles
Tập 7 Số 1 - 2014
FISH mapping of Philadelphia negative BCR/ABL1 positive CML Abstract
Background
Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, almost always characterized by the presence of the Philadelphia chromosome (Ph), usually due to t(9;22)(q34;q11) or its variants. The Ph results in the formation of the BCR/ABL1 fusion gene, which is a constitutively activated tyrosine kinase. Around 1% of CML patients appear to have a Ph negative karyotype but carry a cryptic BCR/ABL1 fusion that can be located by fluorescence in situ hybridisation (FISH) at chromosome 22q11, 9q34 or a third chromosome. Here we present FISH mapping data of BCR and ABL1 flanking regions and associated chromosomal rearrangements in 9 Ph negative BCR/ABL1 positive CML patients plus the cell line CML-T1.
Results
BCR/ABL1 was located at 9q34 in 3 patients, 22q11 in 5 patients and CML-T1 and 22p11 in 1 patient. In 3 of 6 cases with the fusion at 22q11 a distal breakpoint cluster was found within a 280 Kb region containing the RAPGEF1 gene, while in another patient and the CML-T1 the distal breakpoint fell within a single BAC clone containing the 3' RXRA gene. Two cases had a duplication of the masked Ph while genomic deletions of the flanking regions were identified in 3 cases. Even more complex rearrangements were found in 3 further cases.
Conclusion
BCR/ABL1 formation resulted from a direct insertion (one step mechanism) in 6 patients and CML-T1, while in 3 patients the fusion gene originated from a sequence of rearrangements (multiple steps). The presence of different rearrangements of both 9q34 and 22q11 regions highlights the genetic heterogeneity of this subgroup of CML. Future studies should be performed to confirm the presence of true breakpoint hot spots and assess their implications in Ph negative BCR/ABL1 positive CML.
Tập 1 Số 1 - 2008
Cell-free DNA screening for sex chromosome aneuploidies by non-invasive prenatal testing in maternal plasma Abstract
Background
Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, and 13. However, reports on NIPT performance in sex chromosome aneuploidies (SCA) based on real clinical data are still limited.
Methods
High-throughput massively parallel genomic sequencing (MPS) technique was used to screen for fetal SCAs as part of the research to determine the potential value of NIPT in detecting fetal SCAs in the second trimester. A number of 12,243 consecutive cases from a single center were included in this study.
Results
The positive predictive value (PPV) of NIPT in the present study was 57.6%, which was divided and categorized by individual SCAs as follows: 21.4% for Turner syndrome (45,X), 75.0% for Triple X syndrome (47,XXX), 90.9% for Klinefelter syndrome (47,XXY), and 75.0% for XYY syndrome (47,XYY).
Conclusion
The NIPT-based SCA test cannot be used as a diagnostic method, and performing an invasive confirmation test on NIPT-based SCA-positive cases is strongly recommended.
- 2020