Preface

Cytogenetics is the study of chromosome structure and function in relation to phenotypic expression. Chromosomal defects underlie the development of a broad assortment of diseases and conditions ranging from Down syndrome to cancer and are of common concern in both fundamental and clinic research. Chromosomal defects are one of the most common causes of genetic disorders and are responsible for a large proportion of miscarriages. As a result, increasing numbers of parents are becoming interested in genetic counseling in order to learn about the risks of reproductive failure or to understand why they had a child with a particular defect, whether it will happen again, and what might have been done to prevent it. This book discusses the basic biological theory underlying chromosomal abnormalites and provides detalied information on the reproductive risks of chromosomally abnormal individuals and of normal parents.

*Chromosome Abnormalities* is a web-based resource that contains a series of chapters highlighting several aspects related to the generation of chromosomal abnormalities in genetic material. It is an essential resource for cytogeneticists, laboratory personnel, clinicians, research scientists, and students in the field. The book focuses on known or theorized issues directly related to chromosomal abnormalities observed in humans and plants in light of current scientific information in three separate parts: "Introduction", "Chromosomal Abnomalities Observed in Humans" and "Chromosomal Abnomalities Observed in Plants."

In the introductory chapter, Dr. Tülay Aşkın Çelik from Aydın, Turkey, defines, classifies, and provides general information about chromosomal anomalies and how they occur. In addition, the chapter examines the effects of structural and numerical changes in chromosomes, especially on human health. Finally, it emphasizes the importance of classical and molecular cytogenetic techniques in important potential applications, especially in clinical trials and biomedical diagnosis, comparing them against other molecular and genomic methods.

Chapter 2, "The risk a chromosomal abnormalities in cases of minor and major fetal anomalies in the second trimester," by Drs. Beke and Simonyi from Budapest, Hungary, describes the major and minor abnormalities that may occur in normal pregnancy, but that also increase the risk of certain chromosome aberrations. One of the most important techniques for diagnosing chromosomal abnormalities is the fetal ultrasound. In this chapter, researchers emphasize the importance of screening minor and major ultrasound abnormalities in detecting chromosomal abnormalities in the second trimester of pregnancy.

Chapter 3, "Impact of biological factors related to maternal aging: risk of childbirth with Down Syndrome," by Dr. Kumar Dey et al., from West Bengal, India, discusses how maternal aging and multiple biological factors, such as hormones, play a key role in Down syndrome. Hormonal dysfunction also affects the meiotic process and spindle structure integrity and contributes to chromosome nondisjunction. This chapter also discusses the association between maternal age, ovarian aging, environmental factors, and telomere shortening at older reproductive age and the birth of infants with trisomy 21 Down syndrome.

**II**

**Chapter 7 91**

Chromosomal Abnomalities Observed in Plants **113**

**Chapter 8 115**

**Chapter 9 131**

The Energy as a Determinant Factor in the Ethiopathogeny of Chromosomal Abnormalities. The Unsuspected Bioenergetic

Polyploidy in the Ginger Family from Thailand

*by Kesara Anamthawat-Jónsson and Puangpaka Umpunjun*

*by Margarida L.R. Aguiar-Perecin, Janay A. Santos-Serejo,* 

Maize Chromosome Abnormalities and Breakage-Fusion-Bridge

Role of Melanin *by Arturo Solis Herrera*

Cycles in Callus Cultures

*José R. Gardingo and Mateus Mondin*

**Section 3**

Chapter 4, Dr. Ghosh and Dr. Ghosh summarizes "Gene polymorphisms that predispose a women for Down syndrome childbirth," by Dr. Ghosh and Dr. Ghosh from West Bengal, India, summarizes the connection between Down syndrome childbirth and polymorphisms of the genes involved in chromosome division as well as recombination and folic acid metabolisms. They discuss and summarize studies conducted on different population samples from different parts of world to determine the common polymorphisms that can server as markers for preconceptional screening of Down syndrome risk among the women.

Chapter 5, "Current cytogenetic abnormalities in Acute Myeloid Leukemia (AML)," by Dr. Bendari et al. from Casablanca, Morocco, describes typical chromosomal abnormalities in AML. The authors use World Health Organization classifications of AML to adress gene mutations found in normal karyotype AML via cutting-edge, next-generation sequencing technologies such as FLT3-IT, NPM1, CEBPA, and other additional mutations.

Chapter 6, "First-tier array CGH in clinically variable entities diagnosis: 22q13.3 deletion syndrome," by Dr. Budisteanu et al. from Romania, summarizes Phelan-McDermid (PMS) or deletion 22q13 syndrome (OMIM 606232), which is a rare genetic disorder with a highly complex clinical type. PMS genetic defects consist of 22q11.13 deletions or chromosomal structural rearrangements affecting the *SHANK3* gene; lack of *SHANK3* gene function mutations has been reported in a minority of instances. Often there is underdiagnosis of PMS. There are no established clinical diagnostic criteria for PMS and it does not have scientifically defined diagnosis requirements. In this chapter, the researchers identify three cases of PMS and review the clinical and genetic diagnostic methods of this disease, highlighting the function of chromosomal microarray technology in diagnosis of unusual but significant DNA copy number abnormalities

Chapter 7 by Dr. Herrera from the Human Photosynthesis Research Centre in México, describes the unsuspected intrinsic property of melanin to dissociate water molecules, such as chlorophyll in plants, and its implications in the context of chromosomal abnormalities. Chromosome defects, down to the level of the nucleotide, can shed light on the essence of the processes by which normal anatomy forms and abnormal anatomy occurs. It is a daunting challenge to associate genotype with phenotype. Dr. Herrera addresses the energy that guides the development, proper processing, and multiplication of chromosome codes, known as sunlight radiation, through examining melanin.

Chapter 8 "Polyploidy in the ginger family from Thailand," by Dr. Anamthawat-Jónsson from Iceland and Dr. from Umpunjun from Thailand, discusses in detail the taxonomic classification of the ginger family (Zingiberaceae). The ginger family comprises about 50 genera and more than 1300 species worldwide. Approximately 21 genera with about 200 species have been described in Thailand. In this chapter, the researchers include an introduction to Zingiberaceae, which includes the two most cultivated genera, the ginger genus *Zingiber* and the turmeric genus *Curcuma*, and identify their own cytotaxonomic and molecular cytogenetic work on Thailand's *Curcuma* species.

In the final chapter, "Maize chromosome abnormalities and breakage-fusion-bridge cycles in callus cultures," Dr. Aguiar-Perecin et al. from Brazil summarize the maize karyotype, which was first described by the detection of pachytene chromosomes.

**V**

The somatic chromosomes with repeated DNA sequences were detected by C-banding and FISH C-banding, which has helped to classify chromosome abnormalities in callus cultures. In this chapter, the authors focus on heterochromatic knobs implicated in the occurrence of chromosome abnormalities in callus cultures. They found anaphase bridges arising from delayed chromatid separation at knob regions and standard bridges in culture originating from dicentric chromatids, and the phenomenon of uneven crossing over in a knob region was observed in callus culture. These results are of interest for studies on the mechanisms of chromosome

> **Tülay Aşkin Çeli̇k** Department of Biology, Art and Science Faculty,

> > Aydın, Turkey

**Subrata Dey**

Aydın Adnan Menderes University,

Kolkata, West Bengal, India

Maulana Abul Kalam Azad University of Technology (Formerly West Bengal University of Technology),

alterations during evolution.

The somatic chromosomes with repeated DNA sequences were detected by C-banding and FISH C-banding, which has helped to classify chromosome abnormalities in callus cultures. In this chapter, the authors focus on heterochromatic knobs implicated in the occurrence of chromosome abnormalities in callus cultures. They found anaphase bridges arising from delayed chromatid separation at knob regions and standard bridges in culture originating from dicentric chromatids, and the phenomenon of uneven crossing over in a knob region was observed in callus culture. These results are of interest for studies on the mechanisms of chromosome alterations during evolution.

#### **Tülay Aşkin Çeli̇k**

Department of Biology, Art and Science Faculty, Aydın Adnan Menderes University, Aydın, Turkey

#### **Subrata Dey**

Maulana Abul Kalam Azad University of Technology (Formerly West Bengal University of Technology), Kolkata, West Bengal, India

**IV**

Chapter 4, Dr. Ghosh and Dr. Ghosh summarizes "Gene polymorphisms that predispose a women for Down syndrome childbirth," by Dr. Ghosh and Dr. Ghosh from West Bengal, India, summarizes the connection between Down syndrome childbirth and polymorphisms of the genes involved in chromosome division as well as recombination and folic acid metabolisms. They discuss and summarize studies conducted on different population samples from different parts of world to determine the common polymorphisms that can server as markers for

preconceptional screening of Down syndrome risk among the women.

other additional mutations.

through examining melanin.

Thailand's *Curcuma* species.

Chapter 5, "Current cytogenetic abnormalities in Acute Myeloid Leukemia (AML)," by Dr. Bendari et al. from Casablanca, Morocco, describes typical chromosomal abnormalities in AML. The authors use World Health Organization classifications of AML to adress gene mutations found in normal karyotype AML via cutting-edge, next-generation sequencing technologies such as FLT3-IT, NPM1, CEBPA, and

Chapter 6, "First-tier array CGH in clinically variable entities diagnosis: 22q13.3 deletion syndrome," by Dr. Budisteanu et al. from Romania, summarizes Phelan-McDermid (PMS) or deletion 22q13 syndrome (OMIM 606232), which is a rare genetic disorder with a highly complex clinical type. PMS genetic defects consist of 22q11.13 deletions or chromosomal structural rearrangements affecting the *SHANK3* gene; lack of *SHANK3* gene function mutations has been reported in a minority of instances. Often there is underdiagnosis of PMS. There are no established clinical diagnostic criteria for PMS and it does not have scientifically defined diagnosis requirements. In this chapter, the researchers identify three cases of PMS and review the clinical and genetic diagnostic methods of this disease, highlighting the function of chromosomal microarray technology in diagnosis of

Chapter 7 by Dr. Herrera from the Human Photosynthesis Research Centre in México, describes the unsuspected intrinsic property of melanin to dissociate water molecules, such as chlorophyll in plants, and its implications in the context of chromosomal abnormalities. Chromosome defects, down to the level of the nucleotide, can shed light on the essence of the processes by which normal anatomy forms and abnormal anatomy occurs. It is a daunting challenge to associate genotype with phenotype. Dr. Herrera addresses the energy that guides the development, proper processing, and multiplication of chromosome codes, known as sunlight radiation,

Chapter 8 "Polyploidy in the ginger family from Thailand," by Dr. Anamthawat-Jónsson from Iceland and Dr. from Umpunjun from Thailand, discusses in detail the taxonomic classification of the ginger family (Zingiberaceae). The ginger family comprises about 50 genera and more than 1300 species worldwide. Approximately 21 genera with about 200 species have been described in Thailand. In this chapter, the researchers include an introduction to Zingiberaceae, which includes the two most cultivated genera, the ginger genus *Zingiber* and the turmeric genus *Curcuma*,

and identify their own cytotaxonomic and molecular cytogenetic work on

In the final chapter, "Maize chromosome abnormalities and breakage-fusion-bridge cycles in callus cultures," Dr. Aguiar-Perecin et al. from Brazil summarize the maize karyotype, which was first described by the detection of pachytene chromosomes.

unusual but significant DNA copy number abnormalities

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

*Tülay Aşkin Çelik*

tions or chromosomal anomalies.

**1. Introduction**

Introductory Chapter:

Chromosomal Abnormalities

DNA molecules are tightly wrapped around proteins called histones, non-histone

Over the past few decades, genetic and genomic advancements have changed our understanding about health. Genetic anomalies are also related to pregnancy and birth defects. Any disease is partly caused by the individual's genetic characteristics. These genetic abnormalities cause genetic defects that arise as a result of changes (mutations) in a person's DNA. Such variations in DNA occur on nucleotide sequences called genes. In this case, the function of the affected gene(s) may be impaired. The disturbance in the structure of the gene will disturb the normal structure and function of proteins. Mutations change the protein coding sequence of the genome in some way. Nonetheless, there are potentially several different pathways that can impair natural gene expression which can lead to genetic defects. Many genes are dominantly transmitted down the family, in which, the individual bears a regular copy and a modified copy of the gene. The altered gene is therefore prevalent or superior to the regular gene. This occurrence triggers a genetic disorder effect to the child. This case is a spontaneous phenomenon. In all boys and girls, this possibility is the same throughout each birth, and the altered gene cannot be reversed and remain constant in one's life. Many dominant or recessive genetic disorders affect the child from birth, while others have an adult effect on the person only. An organism's genetic component regulates its development and its interplay with its environment. Consequently, any change in this genetic material results in variation in phenotypic characters. These effects can vary, depending on the extent of the aberrations, from being lethal to being harmless. Normally, the cell divisions in daughter cells should have an equal number of chromosomes. The duplicated

proteins that make structures called **chromosomes,** and are present in the cell nucleus as unconcentrated during the cell cycle. Chromosomes are structures inside cells that contain an individual's genes. The human genomes have 46 chromosomes, composed of 22 pairs of autosomes and a pair of sex chromosomes (X and/or Y). All of the somatic cells in females carry two X chromosomes, and all of the somatic cells in males carry one X and one Y chromosome. One half of each pair of chromosomes comes from through the egg cells; one half of each pair comes from through the sperm cells. As a result, females carry two copies of each X-linked gene, while males carry only one copy of X-linked and Y-linked genes. They vary in size and appearance, the X being much somewhat bigger than the Y and contain entirely separate genes, but they do have small areas of resemblance. Both individuals of a species contain the same number of chromosomes specific for that species. Nonetheless, there are individuals that exhibit differences in this standard complement. Such differences may be changes in number of chromosomes or structural changes inside and within chromosomes, collectively such changes are called chromosomal aberra-

#### **Chapter 1**

## Introductory Chapter: Chromosomal Abnormalities

*Tülay Aşkin Çelik*

#### **1. Introduction**

DNA molecules are tightly wrapped around proteins called histones, non-histone proteins that make structures called **chromosomes,** and are present in the cell nucleus as unconcentrated during the cell cycle. Chromosomes are structures inside cells that contain an individual's genes. The human genomes have 46 chromosomes, composed of 22 pairs of autosomes and a pair of sex chromosomes (X and/or Y). All of the somatic cells in females carry two X chromosomes, and all of the somatic cells in males carry one X and one Y chromosome. One half of each pair of chromosomes comes from through the egg cells; one half of each pair comes from through the sperm cells. As a result, females carry two copies of each X-linked gene, while males carry only one copy of X-linked and Y-linked genes. They vary in size and appearance, the X being much somewhat bigger than the Y and contain entirely separate genes, but they do have small areas of resemblance. Both individuals of a species contain the same number of chromosomes specific for that species. Nonetheless, there are individuals that exhibit differences in this standard complement. Such differences may be changes in number of chromosomes or structural changes inside and within chromosomes, collectively such changes are called chromosomal aberrations or chromosomal anomalies.

Over the past few decades, genetic and genomic advancements have changed our understanding about health. Genetic anomalies are also related to pregnancy and birth defects. Any disease is partly caused by the individual's genetic characteristics. These genetic abnormalities cause genetic defects that arise as a result of changes (mutations) in a person's DNA. Such variations in DNA occur on nucleotide sequences called genes. In this case, the function of the affected gene(s) may be impaired. The disturbance in the structure of the gene will disturb the normal structure and function of proteins. Mutations change the protein coding sequence of the genome in some way. Nonetheless, there are potentially several different pathways that can impair natural gene expression which can lead to genetic defects. Many genes are dominantly transmitted down the family, in which, the individual bears a regular copy and a modified copy of the gene. The altered gene is therefore prevalent or superior to the regular gene. This occurrence triggers a genetic disorder effect to the child. This case is a spontaneous phenomenon. In all boys and girls, this possibility is the same throughout each birth, and the altered gene cannot be reversed and remain constant in one's life. Many dominant or recessive genetic disorders affect the child from birth, while others have an adult effect on the person only. An organism's genetic component regulates its development and its interplay with its environment. Consequently, any change in this genetic material results in variation in phenotypic characters. These effects can vary, depending on the extent of the aberrations, from being lethal to being harmless. Normally, the cell divisions in daughter cells should have an equal number of chromosomes. The duplicated

chromosomes must be specifically separated into daughter cells during the cell division. However, too few or too many copies of a chromosome will transfer through daughter cells as a result of cell division errors.

Chromosome abnormalities are mostly the result of a cell division malfunction. A chromosomal abnormality happens when fetus has wrong amount of DNA in a cell; the chromosomes are structurally deficient, or the number of chromosomes is wrong. Additionally, errors can occur in the cell cycle when coping chromosomes. During meiosis division and fertilization, a wide range of chromosomal abnormalities exist; they can be classified into two classes, namely numerical and structural abnormalities. For the gain or loss of a whole chromosome, numerical variations or aneuploidies arise. The resulting phenotypes in a single chromosome or chromosomal fragment are triggered by the mismatch in one or more dosage-sensitive genes. These imbalances in the number of chromosomes also interact with the dosesensitive and developmentally essential genes and ultimately induce the emergence of unique and complex phenotypes [1, 2]. As a consequence, numerical chromosomal aberrations may be symptomatic of tension on DNA replication without actual chromosome segregation defects. Although most human chromosomal DNA dose not encode proteins, even rather small pieces of chromosomes that contain hundreds of genes [3, 4].

A mutation in a chromosome is an unpredictable change. Quite commonly such modifications are caused by complications that arise during meiosis, or by mutagens such as toxins, radiation, viruses, etc. Chromosome mutations may result in changes in cell count or changes in chromosome structure. Mutations in the composition of chromosomes are variations that affect whole chromosomes and whole genomes rather than just individual nucleotides. Chromosome mutations can cause a large variety of genetic disorders. Chromosome abnormalities are also the cause of early pregnancy loss, fetal malformations, stillbirth, and male infertility associated with it. Addition or deletion of entire chromosomes (aneuploidy) will also have fatal consequences. Aneuploid cells exhibits particular defects in the cell cycle kinetics, growth rate, metabolism, and response to specific stresses [3, 5]. Chromosomal disorders may lead to mental retardation or other developmental problems. For more than one system, phenotypic results of a certain gene typically provide details on the biological roles of the particular gene. Furthermore, a deletion or replication of a single gene that may cause other genes affecting several phenotypes are considered pleiotropic genes [2, 6]. Pleiotropy indicates that certain proteins have more than one role in various types of cells, and any genetic alteration that change the gene expression or function of different tissues will theoretically have far-reaching consequences [6, 7].

Contrary to numeric abnormalities, structural chromosomal abnormalities result from a break or breaks that disrupt the continuity of a chromosome. Sometimes a spontaneous break or breaks occur in a chromosome or chromosomes in a different cell which may lead to deletion, inversion, translocation, isochromosome, and ring chromosome [8]. During the cell division, a part of chromosome content is destroyed; the intrinsic rearrangement becomes unbalanced [9]. A disease may arise as a result of a balanced rearrangement if the breaks in the chromosomes occur in a gene, resulting in a missing or nonfunctional protein, or if the fusion of chromosomal segments results in a two gene combination, creating a new protein product whose work damages the cell. Some of the developmental abnormalities found in embryos are closely linked to chromosomal defects that occur, such as mosaism, haploidy, and polyploidy [10–13].

The classical and molecular cytogenetic techniques provide significant potential applications, especially in clinical trials and biomedical diagnosis, rendering them a strong to other molecular and genomic methods and chromosomal abnormalities.

**5**

**Author details**

Tülay Aşkin Çelik

Central Campus, Aydin, Turkey

\*Address all correspondence to: tcelik@adu.edu.tr

provided the original work is properly cited.

Department of Biology, Art and Science Faculty, Aydin Adnan Menderes University,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Introductory Chapter: Chromosomal Abnormalities DOI: http://dx.doi.org/10.5772/intechopen.93404*

care or social support systems.

successful therapies and technologies.

Genetic knowledge can influence not just the entire populations, but the generations come too. Medical genetics' primary aim is to help individuals with a genetic disorder, their families to lead a life as normal as possible, and to provide adequate

Biochemical genetics and cytogenetics work in numerous research fields, such as induce genes defects, chromosome-specific zone recognition, and molecular mechanism of chromosomal abnormalities. The advances in genetic testing using molecular biotechnology and mass screening systems for newborn infants help to understand the role of genes, their behavior, the interaction between genetic diseases and environment, the causes of their appearance, and the development of

#### *Introductory Chapter: Chromosomal Abnormalities DOI: http://dx.doi.org/10.5772/intechopen.93404*

*Chromosomal Abnormalities*

hundreds of genes [3, 4].

have far-reaching consequences [6, 7].

daughter cells as a result of cell division errors.

chromosomes must be specifically separated into daughter cells during the cell division. However, too few or too many copies of a chromosome will transfer through

Chromosome abnormalities are mostly the result of a cell division malfunction. A chromosomal abnormality happens when fetus has wrong amount of DNA in a cell; the chromosomes are structurally deficient, or the number of chromosomes is wrong. Additionally, errors can occur in the cell cycle when coping chromosomes. During meiosis division and fertilization, a wide range of chromosomal abnormalities exist; they can be classified into two classes, namely numerical and structural abnormalities. For the gain or loss of a whole chromosome, numerical variations or aneuploidies arise. The resulting phenotypes in a single chromosome or chromosomal fragment are triggered by the mismatch in one or more dosage-sensitive genes. These imbalances in the number of chromosomes also interact with the dosesensitive and developmentally essential genes and ultimately induce the emergence of unique and complex phenotypes [1, 2]. As a consequence, numerical chromosomal aberrations may be symptomatic of tension on DNA replication without actual chromosome segregation defects. Although most human chromosomal DNA dose not encode proteins, even rather small pieces of chromosomes that contain

A mutation in a chromosome is an unpredictable change. Quite commonly such modifications are caused by complications that arise during meiosis, or by mutagens such as toxins, radiation, viruses, etc. Chromosome mutations may result in changes in cell count or changes in chromosome structure. Mutations in the composition of chromosomes are variations that affect whole chromosomes and whole genomes rather than just individual nucleotides. Chromosome mutations can cause a large variety of genetic disorders. Chromosome abnormalities are also the cause of early pregnancy loss, fetal malformations, stillbirth, and male infertility associated with it. Addition or deletion of entire chromosomes (aneuploidy) will also have fatal consequences. Aneuploid cells exhibits particular defects in the cell cycle kinetics, growth rate, metabolism, and response to specific stresses [3, 5]. Chromosomal disorders may lead to mental retardation or other developmental problems. For more than one system, phenotypic results of a certain gene typically provide details on the biological roles of the particular gene. Furthermore, a deletion or replication of a single gene that may cause other genes affecting several phenotypes are considered pleiotropic genes [2, 6]. Pleiotropy indicates that certain proteins have more than one role in various types of cells, and any genetic alteration that change the gene expression or function of different tissues will theoretically

Contrary to numeric abnormalities, structural chromosomal abnormalities result from a break or breaks that disrupt the continuity of a chromosome. Sometimes a spontaneous break or breaks occur in a chromosome or chromosomes in a different cell which may lead to deletion, inversion, translocation, isochromosome, and ring chromosome [8]. During the cell division, a part of chromosome content is destroyed; the intrinsic rearrangement becomes unbalanced [9]. A disease may arise as a result of a balanced rearrangement if the breaks in the chromosomes occur in a gene, resulting in a missing or nonfunctional protein, or if the fusion of chromosomal segments results in a two gene combination, creating a new protein product whose work damages the cell. Some of the developmental abnormalities found in embryos are closely linked to chromosomal defects that

The classical and molecular cytogenetic techniques provide significant potential applications, especially in clinical trials and biomedical diagnosis, rendering them a strong to other molecular and genomic methods and chromosomal abnormalities.

occur, such as mosaism, haploidy, and polyploidy [10–13].

**4**

Genetic knowledge can influence not just the entire populations, but the generations come too. Medical genetics' primary aim is to help individuals with a genetic disorder, their families to lead a life as normal as possible, and to provide adequate care or social support systems.

Biochemical genetics and cytogenetics work in numerous research fields, such as induce genes defects, chromosome-specific zone recognition, and molecular mechanism of chromosomal abnormalities. The advances in genetic testing using molecular biotechnology and mass screening systems for newborn infants help to understand the role of genes, their behavior, the interaction between genetic diseases and environment, the causes of their appearance, and the development of successful therapies and technologies.

### **Author details**

Tülay Aşkin Çelik

Department of Biology, Art and Science Faculty, Aydin Adnan Menderes University, Central Campus, Aydin, Turkey

\*Address all correspondence to: tcelik@adu.edu.tr

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Hassold T, Chen N, Funkhouser J, Jooss T, Manuel B, et al. A cytogenetic study of 1000 spontaneous abortions. Annals of Human Genetics. 1980;**44**(2):151-178

[2] Theisen A, Shaffer LG. Disorders caused by chromosome abnormalities. The Application of Clinical Genetics. 2010;**3**:159-174

[3] Skvorak Giersch AB, Morton CC. Cytogenetics and cochlear expressed sequence tags (ests) for identification of genes involved in hearing and deafness. In: Keats BJB, Fay RR, Popper AN, editors. Genetics of Auditory Disorders. Springer Handbook of Auditory Research. Vol. 14. New York, NY: Springer; 2002. pp. 92-120

[4] Sansregret L, Vanhaesebroeck B, Swanton C. Determinants and clinical implications of chromosomal instability in cancer. Nature Reviews. Clinical Oncology. 2018;**15**(3):139-150

[5] Malumbres M. Control of the cell cycle. Chapter 4. In: Niederhuber et al., editors. Abeloff's Clinical Oncology. 6th ed. Elsevier; 2014. pp. 52-68

[6] Lobo I. Pleiotropy: One gene can affect multiple traits. Nature Education. 2008;**1**(1):10

[7] Wagner A. The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions. Genetics. 2000;**154**(3):1389-1401

[8] Mitelman F, Johansson B, Mertens F. The impact of translocations and gene fusions on cancer causation. Nature Reviews. Cancer. 2007;**7**(4):233-245

[9] Skvorak Giersch AB. Congenital cytogenetic abnormalities. In: Milunsky A, editor. Genetic Disorders and the Fetus: Diagnosis, Prevention

and Treatment. 5th ed. Vol. 1. Baltimore: The Johns Hopkins University Press; 2004. p. 224

[10] Kloosterman WP, Guryev V, van Roosmalen M, Duran KJ, de Bruijin E, et al. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Human Molecular Genetics. 2011;**20**(10):1916-1924

[11] Liu P, Erez A, Sreenath Nagamani SC, Dhar SU, Kołodziejska KE, Dharmadhikari AV, et al. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell. 2011;**146**(6):889-903

[12] Chiang C, Jacobsen JC, Ersnt C, Hanscom C, Heilbut A, Bluementhal I, et al. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nature Genetics. 2012;**44**(4):390-397

[13] Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, van Binsbrgen E, Renkens I, et al. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Reports. 2012;**1**(6):648-655

**7**

Section 2

Chromosomal

Abnomalities Observed

in Humans

Section 2
