Chromosome abnormalities
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Information on the long-term outlook for individuals with sex chromosome abnormalities is available from studies of infants detected at birth by population studies. Recurrence in a family is exceptional for any of the sex chromosome abnormalities. The great majority of cases of Down syndrome have 47 chromosomes owing to trisomy 21, but in about 5% of cases the chromosome number is normal and the extra chromosomal material is translocated onto another chromosome. The principal form of rearrangement is a reciprocal translocation, where there is an exchange of chromosome material between chromosomes but no change in total chromosome number. Rearrangement of genetic material within a chromosome is usually recognised by chromosome banding techniques but is also revealed by whole genome sequencing. Deletions involve visible loss of a part of a chromosome. Phenotypic features are less severe than when an entire chromosome is lost, so they are seen involving chromosomes where complete loss is incompatible with a full-term pregnancy.
Development of mammalian artificial chromosome vectors: prospects for somatic gene transfer
Nicholas R. Lemoine, David N. Cooper in Gene Therapy, 2020
Mammalian artificial chromosomes (MACs) are being proposed as novel vectors for gene transfer and, potentially, they may be useful for somatic gene therapy. The technical problems inherent in the safe and efficient delivery of genes intact to somatic cells where they are expressed appropriately are a major focus of gene therapy research. The construction of yeast artificial chromosome (YAC) libraries has contributed significantly to the long-range physical, genetic and functional mapping of complex genomes, and proved to be invaluable in localizing and defining new genes. Telo-mere-associated chromosome fragmentation has generated minichromosomes of about 5–7 Mb by a second round of breakage of the human X and Y chromosomes. The second approach is to generate candidate MAC vectors in yeast by recombining YACs containing human telomeres, putative centromere sequences and replication origins, and to transfer the constructs intact into mammalian cells.
Chromosome Folding: Contributions of Chromosome Conformation Capture and Polymer Physics
Guido Tiana, Giorgetti Luca in Modeling the 3D Conformation of Genomes, 2019
This chapter explores the development of molecular genomic approaches for mapping the structure of chromosomes, mainly based on chromosome conformation capture technology. It discusses the development and application of insights from the field of polymer physics to the problem of chromosome folding. The introduction of chromosome conformation capture in 2002 has revolutionized the study of the spatial organization of genomes by allowing mapping of three-dimensional chromosome structure at increasingly high resolution directly to sequence and at the scale of complete genomes. The size of genomes, and thus the number of possible chromatin interactions, makes chromosome conformation capture analysis using PCR impractical. Intra-chromosomal interactions tend to be much more frequent than inter-chromosomal interactions, even for loci separated by hundreds of megabases. The field of chromosome conformation analysis is experiencing a very exciting time of rapid gains in our knowledge of how genomes are organized in space and time and how this relates to regulation of genome function.
Chromosome aberration analysis in atomic bomb survivors and Thorotrast patients using two- and three-colour chromosome painting of chromosomal subsets
Published in International Journal of Radiation Biology, 1996
Chromosomal translocations in peripheral lymphocytes of three healthy Hiroshima atomic (A)-bomb survivors, as well as three Thorotrast patients and two nonirradiated age-matched control persons from the German Thorotrast study were studied by two- and three-colour fluorescence in situ hybridization (chromosome painting) with various combinations of whole chromosome composite probes, including chromosomes 1, 2, 3, 4, 6, 7, 8, 9 and 12. Translocation frequencies detected by chromosome painting in cells of the A-bomb survivors were compared with results obtained by G-banding. A direct comparison was made, i.e. only those cells with simple translocations or complex aberrations detected by G-banding were taken into consideration which in principle could be detected also with the respective painting combination. The statistical analysis revealed no significant differences from a 1:1 relationship between the frequencies of aberrant cells obtained by both methods. The use of genomic translocation frequencies estimated from subsets of chromosomes for biological dosimetry is discussed in the light of evidence that chromosomes occupy distinct territories and are variably arranged in human lymphocyte nuclei. This territorial organization of interphase chromosomes implies that translocations will be restricted to chromatin located at the periphery of adjacent chromosome territories.
Sex chromosome changes in leukemia: cytogenetics and molecular aspects
Published in Hematology, 2018
Saeid Shahrabi, Elahe Khodadi, Fakhredin Saba, Mohammad Shahjahani, Najmaldin Saki
Background and objective: Sex chromosome loss (SCL) can occur in older men as a physiological phenomenon or as an acquired abnormality in leukemia. Loss of chromosome Y and loss of chromosome X are acquired disorders that are mainly observed in patients over 80 years as well as in myeloid and lymphoid malignancies. In this review, we examine the cytogenetic and molecular changes of sex chromosomes in leukemia. Methods: Relevant English language literature were searched and retrieved from PubMed search engine (1990–2016). The following keywords were used: ‘Sex chromosomes’, ‘Leukemia’ and ‘Cytogenetics’. Results: The loss of tumor suppressor genes along with these chromosomal abnormalities in the majority of malignant cells in bone marrow (BM) has raised the question whether this is an age-related phenomenon or has occurred as a result of clonal abnormality. On the other hand, the presence of these chromosomal abnormalities in a number of genetic diseases associated with leukemia leads to progression of malignancy, and their role in peripheral blood stem cell transplantation confirm the finding that these chromosomal abnormalities can play an important role in clonal abnormality. Conclusion: The presence of these abnormalities can cause genetic instability in BM and result in the development of a malignant clone and progression of the disease. In addition, the evaluation of SCL together with the genes involved in these chromosomes can contribute to predict the disease prognosis as well as monitoring of malignancy.
Investigation of the Frequencies of Prenatally Diagnosed Fetal Chromosomal Abnormalities at a Single Institution
Published in Fetal and Pediatric Pathology, 2013
Qichang Wu, Wenbo Wang, Hui Kong, Li Sun, Yunsheng Ge, Yasong Xu, Yulin Zhou
The objective of this study was to investigate, retrospectively, the frequencies of fetal chromosomal abnormalities identified in 4176 prenatal cytogenetic examinations at the Xiamen Maternity and Child Health Care Hospital over the 5-year period from October 2005 to September 2010. The frequency of abnormal fetal karyotypes was 4.6%. Numerical chromosome abnormalities were identified in 150 cases. The frequency of trisomy 21 was by far the highest, followed by trisomy 18. Structural aberrations of chromosomes were identified in 43 cases, including 21 cases with balanced and 22 cases with unbalanced chromosomal aberrations. In addition, 16 cases of apparently de novo chromosomal aberrations and 27 cases of familial inheritances were observed. Increased awareness of the frequencies of fetal chromosome abnormalities is important for the improvement of prenatal care and providing the options of termination or continuation of the pregnancy. Data obtained in this study provide the basis of a database for genetic counseling.
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