Chromosome abnormality

of an individual with trisomy 21, showing three copies of chromosome 21. daughter cells with 4 sets of chromosomes instead of two Maintaining a euploid state, where cells contain the correct number of chromosome sets, is essential for genomic stability. Aneuploidy, characterized by an abnormal number of chromosomes, occurs when an individual is missing a chromosome from a pair (monosomy) or has an additional chromosome (trisomy). Aneuploidy may arise from meiosis segregation errors such as nondisjunction, premature disjunction, or anaphase lag during meiosis I or II. For aneuploidy, nondisjunction, the most frequent error, particularly in oocyte formation, occurs when replicated chromosomes fail to separate properly, leading to germ cells with an extra or missing chromosome. Polyploidy encompasses various forms, including triploid (three sets of chromosomes) and tetraploid (four sets of chromosomes). Rather than having monosomy, or only one copy, the majority of aneuploid people have trisomy, or three copies of one chromosome. An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X. Sperm aneuploidy Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. In particular, risk of aneuploidy is increased by tobacco smoking, and occupational exposure to benzene, insecticides, and perfluorinated compounds. Increased aneuploidy is often associated with increased DNA damage in spermatozoa. ==Structural abnormalities==

Structural abnormalities in chromosomes may result from breakage and improper realignment of chromosome segments. To expand, these abnormalities may be defined as follows: • Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere. ==Inheritance==

Constitutional chromosome abnormalities (present at beginning of development) arise during gametogenesis or embryogenesis, affecting a significant proportion of an organism's cells. These inherited abnormalities most commonly occur as errors in the egg or sperm, meaning the anomaly is present in every cell of the body. The diseases that follow a single-gene inheritance pattern are relatively rare but affect millions of individuals. • Autosomal dominant: Where at least one affected parent passes the mutation, and the condition appears in every generation. Chromosomal abnormalities can also arise from de novo mutations within an individual. De novo mutations are spontaneous, somatic mutations that occur without prior inheritance, and they can emerge at various stages of life, including during the parental germline, embryonic or fetal development, or later in life due to aging. These mutations may occur during gametogenesis or postzygotically, resulting in new mutations that appear in a single generation without prior evidence of mutation in the parental chromosomes. Approximately 7% of de novo mutations are present as high-level mosaic mutations. Genetic mosaicism, which refers to a post-zygotic mutation, occurs when an individual possesses two or more genetically distinct cell populations derived from a single fertilized egg. This can lead to chromosomal abnormalities, and these mutations may be present in somatic cells, germ cells, or both, in the case of gonosomal mosaicism, where mutations exist in both somatic and germline cells. Somatic mosaicism involves multiple cell lineages in somatic cells, while germline mosaicism occurs in multiple lineages within germline cells, allowing the mutation to be passed to offspring. An example of a chromosomal abnormality resulting from genetic mosaicism is Turner syndrome. ==Acquired chromosome abnormalities==

Acquired chromosomal abnormalities represent genetic alterations that manifest during an individual's lifetime, as opposed to being inherited from their parents. In contrast to constitutional chromosomal abnormalities, which are present at birth, acquired abnormalities occur during adulthood and are confined to specific clones of cells, thereby inhibiting their distribution throughout the body. Spontaneous replication errors typically occur due to DNA polymerase synthesizing new polynucleotides while evading proofreading functions, leading to mismatches in base pairing. Mutagens can be classified as physical, chemical, or biological: • Chemical: Common chemical mutagens include base analogs (molecules that resemble nitrogenous bases), deaminating agents (which remove amino groups), alkylating agents, and intercalating agents. Transposons and IS can move through DNA by 'jumping,' disrupting the functionality of chromosomal DNA. The insertion of viral DNA can lead to genetic disruption, while bacteria may produce reactive oxygen species (ROS) that cause inflammation and DNA damage, resulting in decreased repair efficiency. with either the formation of hybrid genes and fusion proteins, deregulation of genes and overexpression of proteins, or loss of tumor suppressor genes (see the "Mitelman Database" and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,). Approximately 90% of cancers exhibit chromosomal instability (CIN), characterized by the frequent gain or loss of entire chromosome segments. This phenomenon contributes to tumor aneuploidy and intra-tumor heterogeneity, which are commonly observed in most human cancers. ==DNA damage during spermatogenesis==

DNA damage during spermatogenesis plays a crucial role in chromosomal abnormalities and male fertility. In the early stages of sperm development, DNA repair mechanisms such as homologous recombination (HR) and mismatch repair (MMR) efficiently correct replication errors and double-strand breaks (DSBs). However, as spermatogenesis progresses, DNA repair capacity declines due to changes in how DNA is packaged inside sperm cells. Spermatogenesis occurs in three phases: mitosis (spermatocytogenesis), meiosis, and spermiogenesis. During spermiogenesis, the DNA becomes more tightly packed to fit inside the sperm head. This happens because histone proteins, which normally help organize DNA, are replaced with transition proteins (TNP1, TNP2) and then protamines (PRM1, PRM2). While this packaging protects the DNA, it also makes it harder for repair enzymes to fix any damage. As a result, non-homologous end joining (NHEJ), an error-prone repair process, becomes the main repair mechanism, increasing the risk of mutations. Oxidative stress is another major factor contributing to DNA damage in sperm cells. Reactive oxygen species (ROS), produced both inside sperm and from external sources such as immune cells in seminal fluid, can break DNA strands. High ROS levels can overwhelm antioxidant defences, leading to further damage and triggering cell death pathways. Normally, defective sperm cells are removed through apoptosis, a controlled cell death process. However, if this system fails—such as when there is an imbalance between pro-apoptotic (BAX) and anti-apoptotic (BCL-2) factors—damaged sperm may survive. If these sperm fertilize an egg, the oocyte's repair mechanisms may attempt to fix the damage. The maternal repair machinery is capable of correcting sperm DNA damage post-fertilization, but errors in this process can result in chromosomal structural aberrations in the developing zygote. Notably, exposure to DNA-damaging agents, such as the chemotherapy drug Melphalan, can induce inter-strand DNA crosslinks that escape paternal repair, potentially leading to chromosomal abnormalities due to maternal misrepair. Therefore, both pre- and post-fertilization DNA repair are crucial for maintaining genome integrity and preventing genetic defects in the offspring. DNA damage in sperm has been linked to infertility, increased miscarriage risk, and conditions such as aneuploidy and structural chromosomal rearrangements. Understanding how DNA damage occurs and is repaired during spermatogenesis is important for studying male reproductive health and genetic inheritance. == Detection ==

Chromosomal abnormalities can be detected at either postnatal testing or prenatal screening, which includes prenatal diagnosis. Early detection is crucial for enabling parents to assess their upcoming pregnancy options. Common techniques used to detect diseases resulting from chromosomal abnormalities: • Karyotyping • Fluorescence in situ hybridization (FISH) Karyotyping has been the traditional method used to detect chromosomal abnormalities. It requires entire set of chromosomes to be able to identify fetal aneuploidy and variations in structural arrangements, which could be a result of insertions, inversions, duplications or deletions of chromosomes. For the treatment of MM relapse, acquired chromosomal abnormalities such as del (17p), amp (1q) and Tetraploidy can be analyzed to guide future therapy development and updated prognosis. Through the use of fluorescent dyes such as Cy5, Texas red and spectrum green, 24 distinguishable colors can be generated using imaging spectroscopy. Depending on the information one wants to obtain, different techniques and samples are needed. • For the prenatal diagnosis of a fetus, amniocentesis, chorionic villus sampling, or circulating foetal cells would be collected and analysed in order to detect possible chromosomal abnormalities. • For the preimplantational diagnosis of an embryo, a blastocyst biopsy would be performed. • For a lymphoma or leukemia screening the technique used would be a bone marrow biopsy. ==Nomenclature==

File:Three chromosomal abnormalities with ISCN nomenclature.png|Three chromosomal abnormalities with ISCN nomenclature, with increasing complexity: (A) A tumour karyotype in a male with loss of the Y chromosome, (B) Prader–Willi Syndrome i.e. deletion in the 15q11-q12 region and (C) an arbitrary karyotype that involves a variety of autosomal and allosomal abnormalities. File:Human karyotype with bands and sub-bands.png|Human karyotype with annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen on G banding. Each row is vertically aligned at centromere level. It shows 22 homologous autosomal chromosome pairs, both the female (XX) and male (XY) versions of the two sex chromosomes, as well as the mitochondrial genome (at bottom left). The International System for Human Cytogenomic Nomenclature (ISCN) is an international standard for human chromosome nomenclature, which includes band names, symbols and abbreviated terms used in the description of human chromosome and chromosome abnormalities. Abbreviations include a minus sign (-) for chromosome deletions, and del for deletions of parts of a chromosome. == See also ==