Science and Technology Production
Book Chapter
Authorship
SOLONESKI, SONIA MARIA ELSA
;
Larramendy, M.L.
Date
2017
Publishing House and Editing Place
INTECH Publisher
Book
Chromosomal Abnormalities ? A Hallmark Manifestation of Genomic Instability
(pp. 8-9)
INTECH Publisher
INTECH Publisher
ISBN
978-953-51-3473-2
Summary
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SIGEVA
Genome replication is a highly conserved, essential biological process to preserve genetic information across generations. Perturbations in genome replication represent significant challenges for cells from prokaryotic and eukaryotic organisms. Thus, this process needs to be highly regulated to occur only once per cell cycle in order to ensure the preservation of genome integrity and to promote faithful genome propagation from a parental cell to the two daughter cells. Living cells have develop...
Genome replication is a highly conserved, essential biological process to preserve genetic information across generations. Perturbations in genome replication represent significant challenges for cells from prokaryotic and eukaryotic organisms. Thus, this process needs to be highly regulated to occur only once per cell cycle in order to ensure the preservation of genome integrity and to promote faithful genome propagation from a parental cell to the two daughter cells. Living cells have developed several mechanisms to preserve genome stability. The genome replication process includes several aspects to ensure the fidelity of DNA replication, an efficient DNA repair system, if required, and an optimal mechanical mechanism for achieving a normal segregation of the genetic material into the daughter cells. Genomic instability in the form of mutations and chromosomal abnormalities has a key role in pathological disorders as well as in the evolution process by generating genetic variation. Chromosomal instability is a process that leads to cells with unbalanced genomes, containing both numerical and/or structural abnormalities. For more than a century, the loss of stability of the genome has been and is still accepted as one of the most important aspects of carcinogenesis. In humans, it is often associated with premature ageing and with inherited diseases. Chromosomal abnormalities have been recognized for a long time and have generally proven to be a highly specific biomarker of malignancy in the majority of, if not all, neoplastic processes. Furthermore, it well known that chromosomal abnormalities represent one of the leading causes of pregnancy loss and developmental disabilities, and are the highest risk factor that might contribute to the natural ageing process. Understanding the structural and molecular bases of chromosomal abnormalities remains a basic challenge in cellular biology in general, and in cytogenetics in particular.Chromosomal abnormalities are mainly classified into two groups, structural aberrations and numerical alterations. Structural rearrangements encompass several different classes of events such as gene amplification or deletion, translocation, duplication, inversion, ring formation, whereas numerical abnormalities include euploidy or aneuploidy. Structural chromosome abnormalities can originate from DNA breakage of the double helices in the genome at two different locations, followed by a rejoining of the broken ends to produce a new chromosomal rearrangement, whereas numerical abnormalities can form through various errors in the mitotic spindle checkpoint and some cellular processes during mitosis. Numerous genetic testing methodologies have been developed rapidly over the last decade, including cytogenetic, biochemical, and molecular approaches, to detect these different types of abnormalities. However, the causes and consequences of these aberrations still remain far from being fully understood. Thus, further investigations into the mechanisms of the origins of chromosomal instability would broaden insights regarding the structure and function of chromosomes. This single volume comprises ten high-quality chapters describing the implications of the generation of chromosomal abnormalities in genetic material. The first chapter comprises an excellent review about the general principles of chromosomal abnormalities and the molecular cytogenetic techniques that can help in the identification of the presence or absence of a particular DNA sequence or the evaluation of the number or organization of chromosomes or a chromosomal region, as well as the importance of the employing these methodologies in diagnostic procedures in numerous areas of clinical medicine, including haematology, perinatology, and obstetrics. This is followed by a second chapter providing information from morphological markers of chromosomal instability employed for prognoses of cancers, with special emphasis on descriptions of atypical mitosis including multipolar, ring, dispersed, asymmetrical, and lag-type mitoses as well as nuclear atypia such as micronuclei formation. The third chapter presents an update in the field, describing the acquired structural and numerical chromosomal abnormalities in solid tumors, and presents potential formation mechanisms. In this chapter, the relationship between long inverted repeat sequences and MYCN oncogene amplification in neuroblastoma is also discussed. The fourth chapter discusses specific treatment options, including allogeneic hematopoietic stem cell transplantation in both acute myeloid and acute lymphoblastic patients, with some prognostically proven cytogenetic variants such as the presence of hyperdiploid karyotypes, monosomies, and complex chromosomal rearrangements. The fifth chapter provides an overview about the occurrence of the aneuploidy process in brain cells from normal individuals and Alzheimer?s patients as well as a discussion of the possible mechanisms to explain the origin of aneuploidy and the pros and cons of different techniques used to analyze aneuploidy in brain cells. The sixth chapter presents a contribution showing how X chromosome abnormalities as well as low-level mosaicism for this chromosome can be implicated in reproductive consequences in phenotypically normal women with recurrent pregnancy loss and/or fertility problems. The seventh chapter is a detailed overview about the applications of two genetic tests, preimplantation genetic diagnosis (also known as PGD) and preimplantation genetic screening (also known as PGS), for the estimation of translocations and detection of aneuploidy, respectively. The eighth chapter highlights how a decrease in expression of the basic transcription factor TRF2 can result in chromatin condensation abnormalities in a validated experimental organism model, Drosophila sp. is. The ninth chapter presents a description of normal karyotypes and chromosomal abnormalities through comprehension of chromosomal variation within fruit fly populations as models for studying genetic polymorphisms. The book ends with a chapter describing a hypothesis showing how frying pan--shaped chromosomes are formed by sister chromatid exchanges and a premature kinetochore movement in prophase II in two agave plants, Agave stricta and A. angustifolia. Furthermore, the authors postulate the presence of genes that are prone to act under diverse kinds of environmental stress.The editors of Chromosomal Abnormalities - Hallmark Manifestations of Genomic Instability are enormously grateful to all the contributing authors for sharing their knowledge and insight in this book project. They have made an extensive effort to arrange the information included in every valuable chapter. This book is designed to provide an introduction and overview and could be consulted by scientific readers and readers not familiar with the field. The publication of this book is of high importance for those researchers, scientists, biologists, geneticists, and veterinarians, as well as teachers and advanced-level students, who make use of these different investigations to understand the origin and implications of chromosomal aberrations and to guide them in the future investigations.
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Key Words
PollutantsDNAChromosomal damage