{{short description|Abnormal number or structure of chromosomes}} {{distinguish|Chromatic aberration}} {{cs1 config|name-list-style=vanc|display-authors=6}}
A '''chromosomal abnormality''' or '''chromosomal anomaly''' is a missing, extra, or irregular portion of [[Chromosome|chromosomal]] DNA.<ref name="cite419cd721">{{cite book | chapter = Chromosomal Abnormalities |date=2009-07-08 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK115545/ | title = Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals |access-date=2023-09-27 |publisher=Genetic Alliance |language=en}}</ref><ref>{{cite web | work = NHGRI | date = 2006 | url = http://www.genome.gov/11508982 | title = Chromosome Abnormalities Fact Sheet | archive-url = https://web.archive.org/web/20060925215457/http://www.genome.gov/11508982 | archive-date=2006-09-25 }} {{source attribution}}</ref> These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. '''Chromosome mutation''' was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one [[gene]].<ref>{{cite book | vauthors = Rieger R, Michaelis A, Green M | chapter = Mutation | title = A glossary of genetics and cytogenetics: Classical and molecular | location = New York | year = 1968 | chapter-url = https://archive.org/details/glossaryofgeneti00rieg | chapter-url-access = registration | publisher = Springer-Verlag | isbn = 978-0-387-07668-3 }}</ref> Chromosome anomalies usually occur when there is an error in [[cell division]] following [[meiosis]] or [[mitosis]]. Chromosome abnormalities may be detected or confirmed by comparing an individual's [[karyotype]], or full set of chromosomes, to a typical karyotype for the [[species]] via [[genetic testing]].
Sometimes chromosomal abnormalities arise in the early stages of an [[embryo]], [[sperm]], or [[infant]].<ref>{{Cite book | vauthors = Chen H | title = Atlas of genetic diagnosis and counseling | location = Totowa, N.J | date = 2006 | publisher = Humana Press | isbn = 978-1-58829-681-8 }}</ref> They can be caused by various environmental factors. The implications of chromosomal abnormalities depend on the specific problem, they may have quite different ramifications.{{Citation needed|date=September 2025}} Diseases and conditions caused by chromosomal abnormalities are called '''chromosomal disorders''' or '''chromosomal aberrations'''.<ref>{{Cite book |last=Manglik |first=Mr Rohit |url=https://books.google.com/books?id=VEtZEQAAQBAJ&pg=PA529 |title=Veterinary General Pathology |date=2024-04-24 |publisher=EduGorilla Publication |isbn=978-93-7115-241-9 |page=529 |language=en}}</ref> Some examples are [[Down syndrome]] and [[Turner syndrome]].<!-- No sources are specified --> However, chromosomal abnormalities do not always lead to diseases. Among abnormalities, structural rearrangements of genes between chromosomes can be harmless if they are balanced, which means that a set of the chromosomes remains complete and there are no gene breaks across the chromosomes.<ref>{{Cite Q|Q136041435|page=72}}</ref>
==Numerical abnormality== [[File:Down Syndrome Karyotype.png|thumb|A [[karyotype]] of an individual with [[Down syndrome|trisomy 21]], showing three copies of chromosome 21. ]] [[File:Polyploidization.svg|thumb|Error within meiosis segregation resulting in [[tetraploid]] daughter cells with 4 sets of chromosomes instead of two]] Maintaining a [[Euploid|euploid state]], where cells contain the correct number of chromosome sets, is essential for genomic stability.<ref name="Orr_2015">{{cite journal | vauthors = Orr B, Godek KM, Compton D | title = Aneuploidy | journal = Current Biology | volume = 25 | issue = 13 | pages = R538–R542 | date = June 2015 | pmid = 26126276 | pmc = 4714037 | doi = 10.1016/j.cub.2015.05.010 | language = English | bibcode = 2015CBio...25.R538O }}</ref> [[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]]).<ref name="cite88fb9177" /><ref name="citecd5d94e4" /><ref name="Gardner_2012" /> This may be either full, involving a whole chromosome, or partial, where only part of a chromosome is missing or added.<ref name="cite88fb9177">{{Cite book | title = Chromosome abnormalities and genetic counseling {{!}} WorldCat.org|oclc=769344040|language=en}}</ref><ref name="citecd5d94e4">{{Cite web | title = Content - Health Encyclopedia - University of Rochester Medical Center | url = https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=90&contentid=P02138 | access-date = 2025-04-03 | website = www.urmc.rochester.edu }}</ref><ref name="Gardner_2012">{{Cite book | title = Chromosome abnormalities and genetic counseling | location = Oxford | date = 2012 | vauthors = Gardner RJ, Sutherland GR, Shaffer LG | publisher = Oxford University Press | isbn = 978-0-19-974915-7 | edition = 4th | oclc = 769344040 }}</ref> Aneuploidy may arise from [[meiosis]] segregation errors such as [[nondisjunction]], premature disjunction, or [[anaphase lag]] during meiosis I or II.<ref name="Queremel_2025">{{cite book | vauthors = Queremel Milani DA, Tadi P| chapter = Genetics, Chromosome Abnormalities |date=2025 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK557691/ |access-date=2025-04-03 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491623 }}</ref> For aneuploidy, nondisjunction, the most frequent error, particularly in [[oocyte]] formation, occurs when replicated chromosomes fail to separate properly, leading to [[Germ cell|germ cells]] with an extra or missing chromosome.<ref name="Queremel_2025" /> Additionally, [[polyploidy]] occurs when cells contain more than two sets of chromosomes.<ref>{{cite journal | vauthors = Potapova T, Gorbsky GJ | title = The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis | journal = Biology | volume = 6 | issue = 1 | page = 12 | date = February 2017 | pmid = 28208750 | pmc = 5372005 | doi = 10.3390/biology6010012 | doi-access = free | bibcode = 2017Biol....6...12P }}</ref> Polyploidy encompasses various forms, including [[triploid]] (three sets of chromosomes) and [[tetraploid]] (four sets of chromosomes).<ref name="Orr_2015" /> Tetraploidy often arises from developmental errors during mitosis, such as [[Cytokinesis|cytokinesis failure]], [[Endoreduplication|endoreplication]], mitotic slippage, and cell fusion. These errors can subsequently lead to aneuploidy.<ref name="Orr_2015" /> [[File:45,X.jpg|thumb|A [[karyotype]] of an individual with [[Turner syndrome|Turner Syndrome]], where there is only a single X chromosome.]] Aneuploidy can occur with [[sex chromosome]]s or [[autosome]]s.<ref>{{Cite web | title = Chromosomal Abnormalities: Aneuploidies {{!}} Learn Science at Scitable|url=https://www.nature.com/scitable/topicpage/chromosomal-abnormalities-aneuploidies-290/|access-date=2025-04-04|website=www.nature.com|language=en}}</ref> Rather than having monosomy, or only one copy, the majority of aneuploid people have trisomy, or three copies of one chromosome.<ref name="cite419cd721" /> An example of trisomy in humans is [[Down syndrome]], which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called "trisomy 21".<ref>{{cite journal | vauthors = Patterson D | title = Molecular genetic analysis of Down syndrome | journal = Human Genetics | volume = 126 | issue = 1 | pages = 195–214 | date = July 2009 | pmid = 19526251 | doi = 10.1007/s00439-009-0696-8 | s2cid = 10403507 }}</ref> An example of monosomy in humans is [[Turner syndrome]], where the individual is born with only one sex chromosome, an X.<ref>{{Cite web | title = Turner Syndrome | url = https://www.nichd.nih.gov/health/topics/turner | access-date = 2020-11-17 | website = National Institute of Child Health and Human Development | language = en }}</ref>
===Sperm aneuploidy=== Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of [[Aneuploidy|aneuploid]] [[spermatozoa]].<ref name="Templado_2013">{{cite journal | vauthors = Templado C, Uroz L, Estop A | title = New insights on the origin and relevance of aneuploidy in human spermatozoa | journal = Molecular Human Reproduction | volume = 19 | issue = 10 | pages = 634–643 | date = October 2013 | pmid = 23720770 | doi = 10.1093/molehr/gat039 }}</ref> In particular, risk of aneuploidy is increased by [[Tobacco smoking#Health|tobacco smoking]],<ref name="Shi_2001">{{cite journal | vauthors = Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R | title = Cigarette smoking and aneuploidy in human sperm | journal = Molecular Reproduction and Development | volume = 59 | issue = 4 | pages = 417–421 | date = August 2001 | pmid = 11468778 | doi = 10.1002/mrd.1048 | s2cid = 35230655 }}</ref><ref name="Rubes_1998">{{cite journal | vauthors = Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ | title = Smoking cigarettes is associated with increased sperm disomy in teenage men | journal = Fertility and Sterility | volume = 70 | issue = 4 | pages = 715–723 | date = October 1998 | pmid = 9797104 | doi = 10.1016/S0015-0282(98)00261-1 | doi-access = free }}</ref> and occupational exposure to [[benzene]],<ref name="Xing_2010">{{cite journal | vauthors = Xing C, Marchetti F, Li G, Weldon RH, Kurtovich E, Young S, Schmid TE, Zhang L, Rappaport S, Waidyanatha S, Wyrobek AJ, Eskenazi B | title = Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy | journal = Environmental Health Perspectives | volume = 118 | issue = 6 | pages = 833–839 | date = June 2010 | pmid = 20418200 | pmc = 2898861 | doi = 10.1289/ehp.0901531 | bibcode = 2010EnvHP.118..833X }}</ref> [[insecticide]]s,<ref name="Xia_2004">{{cite journal | vauthors = Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X | title = Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate | journal = Toxicology | volume = 203 | issue = 1–3 | pages = 49–60 | date = October 2004 | pmid = 15363581 | doi = 10.1016/j.tox.2004.05.018 | s2cid = 36073841 | bibcode = 2004Toxgy.203...49X }}</ref><ref name="Xia_2005">{{cite journal | vauthors = Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X | title = Genotoxic effects on spermatozoa of carbaryl-exposed workers | journal = Toxicological Sciences | volume = 85 | issue = 1 | pages = 615–623 | date = May 2005 | pmid = 15615886 | doi = 10.1093/toxsci/kfi066 | doi-access = free }}</ref> and [[perfluorinated compound]]s.<ref name="Governini_2015">{{cite journal | vauthors = Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P | title = Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds | journal = Andrologia | volume = 47 | issue = 9 | pages = 1012–1019 | date = November 2015 | pmid = 25382683 | doi = 10.1111/and.12371 | s2cid = 13484513 | doi-access = free | hdl = 11365/982323 }}</ref> Increased aneuploidy is often associated with increased DNA damage in spermatozoa.
==Structural abnormalities== [[File:Single Chromosome Mutations.svg|thumb|right|The three major single-chromosome mutations: deletion (1), duplication (2) and inversion (3).|233x233px]] [[File:Two Chromosome Mutations.png|thumb|The two major two-chromosome mutations: insertion (1) and translocation (2).|330x330px]] Structural abnormalities in chromosomes may result from breakage and improper realignment of chromosome segments.<ref name="cite419cd721" /> When the structure of a chromosome is altered, it can result in unbalanced rearrangements, balanced rearrangements, ring chromosomes, and isochromosomes.<ref name="cite419cd721" /><ref name="citebf75f7ae">{{cite web | title = Chromosome Abnormalities | url = http://atlasgeneticsoncology.org/Educ/PolyMecaEng.html | url-status = live | archive-url = https://web.archive.org/web/20060814044124/http://atlasgeneticsoncology.org/Educ/PolyMecaEng.html | archive-date = 14 August 2006 | access-date = 9 May 2018 | website = atlasgeneticsoncology.org }}</ref> To expand, these abnormalities may be defined as follows: <ref name="cite419cd721" /><ref name="citebf75f7ae" /> * Unbalanced rearrangements includes missing or additional genetic information in chromosomes.<ref name="cite419cd721" /> They include: ** [[Deletion (genetics)|Deletions]]: A portion of the chromosome is missing or has been deleted.<ref name="cite419cd721" />Known disorders in humans include [[Wolf–Hirschhorn syndrome]], which is caused by partial deletion of the [[short arm]] of chromosome 4; and [[Jacobsen syndrome]], also called the terminal 11q deletion disorder.<ref name="citebf75f7ae" /> ** [[chromosomal duplication|Duplications]]: A portion of the chromosome has been duplicated, resulting in extra genetic material.<ref name="cite419cd721" /> Known human disorders include [[Charcot–Marie–Tooth disease type 1A]], which may be caused by duplication of the gene encoding [[peripheral myelin protein 22]] (PMP22) on chromosome 17.<ref name="citebf75f7ae" /> ** [[Insertion (genetics)|Insertions]]: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.<ref name="cite419cd721" /> * Balanced rearrangements includes the alteration of chromosome segments but the genetic information is not lost or gained.<ref name="cite419cd721" /> They include: ** [[Chromosomal inversion|Inversions]]: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted.<ref name="cite419cd721" /> ** [[Chromosomal translocation|Translocation]]s: A portion of one chromosome has been transferred to another chromosome.<ref name="cite419cd721" /> There are two main types of translocations: *** [[Chromosomal translocation#Reciprocal translocations|Reciprocal translocation]]: Segments from two different chromosomes have been exchanged.<ref name="citebf75f7ae" /> *** [[Robertsonian translocation]]: A pair of chromosomes break at their [[Centromere|centromeres]], lose their [[Locus (genetics)|short p arms]], and fuse at their [[Locus (genetics)|q arms]], forming a single chromosome with one centromere.<ref name="cite419cd721" /> This type of translocation typically occurs between chromosomes 13, 14, 15, 21, and 22 in humans.<ref name="citebf75f7ae" /> [[File:202206 Robertsonian translocation.svg|center|thumb|201x201px|Robertsonian translocation. Two chromosomes with the removal of their p (short) arms, and fusion at the centromere with their q (long) arms.]] * [[Ring chromosome|Rings]]: A portion of a chromosome (the ends) has broken off and formed a circle or ring. This happens with or without the loss of genetic material.<ref name="cite419cd721" /> [[File:202206 Ring chromosome.svg|center|thumb|186x186px|Formation of a ring chromosome]]
* [[Extrachromosomal DNA|Extrachromosomal DNA (ecDNA)]]: 100 kb to 5 Mb-sized circular DNA molecules found in the nucleus that undergo [[non-Mendelian inheritance]] and do not have detectable centromeric activity. A primary mechanism for ecDNA formation is [[chromothripsis]]. Since ecDNA can reach high copy numbers and possesses highly-accessible chromatin, it can drive massive oncogene expression in cancer and is associated with poor clinical outcomes<ref>{{Cite journal |last1=Wu |first1=Sihan |last2=Bafna |first2=Vineet |last3=Chang |first3=Howard Y. |last4=Mischel |first4=Paul S. |date=2022-01-24 |title=Extrachromosomal DNA: An Emerging Hallmark in Human Cancer |journal=Annual Review of Pathology: Mechanisms of Disease |language=en |volume=17 |pages=367–386 |doi=10.1146/annurev-pathmechdis-051821-114223 |pmid=34752712 |pmc=9125980 |issn=1553-4006}}</ref><ref>{{Cite journal |last1=Yost |first1=Kathryn E. |last2=Zhao |first2=Yanding |last3=Hung |first3=King L. |last4=Zhu |first4=Kaiyuan |last5=Xu |first5=Duo |last6=Corces |first6=M. Ryan |last7=Shams |first7=Shadi |last8=Louie |first8=Bryan H. |last9=Sarmashghi |first9=Shahab |last10=Sundaram |first10=Laksshman |last11=Luebeck |first11=Jens |last12=Clarke |first12=Stanley |last13=Doane |first13=Ashley S. |last14=Granja |first14=Jeffrey M. |last15=Choudhry |first15=Hani |date=May 2025 |title=Three-dimensional genome landscape of primary human cancers |journal=Nature Genetics |language=en |volume=57 |issue=5 |pages=1189–1200 |doi=10.1038/s41588-025-02188-0 |pmid=40355593 |pmc=12081301 |issn=1546-1718}}</ref>
* [[Isochromosome]]: Formed by the mirror image copy of a chromosome segment including the centromere.<ref name="citebf75f7ae" /> Specifically, they form when one arm of a chromosome is lost, and the remaining arm duplicates.<ref name="cite419cd721" /> [[File:202206 Isochromosome.svg|center|thumb|Isochromosome formation]] [[Chromosome instability syndrome]]s are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.<ref>{{cite book | vauthors = Rayi A, Hozayen A | chapter = Chromosome Instability Syndromes |date=2025 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK537198/ |access-date=2025-04-04 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30725883 }}</ref>
==Inheritance== [[File:Autosomal recessive and dominant.png|thumb|Autosomal dominant and autosomal recessive inheritance patterns]] Constitutional chromosome abnormalities (present at beginning of development) arise during [[gametogenesis]] or embryogenesis, affecting a significant proportion of an organism's cells.<ref name="McFadden_1997">{{cite journal | vauthors = McFadden DE, Friedman JM | title = Chromosome abnormalities in human beings | journal = Mutation Research | volume = 396 | issue = 1–2 | pages = 129–140 | date = December 1997 | pmid = 9434864 | doi = 10.1016/S0027-5107(97)00179-6 | bibcode = 1997MRFMM.396..129M }}</ref> These inherited abnormalities most commonly occur as errors in the [[egg]] or [[sperm]], meaning the anomaly is present in every cell of the body.<ref name="cite419cd721" /> Factors such as maternal age and environmental influences contribute to the occurrence of these genetic errors.<ref name="cite419cd721" /> Offspring inherit two copies of each gene, one from each parent, and mutations (often caused by disease) may be passed down through generations.<ref name="Alliance_2009">{{cite book |author1=Genetic Alliance |author2=The New York-Mid-Atlantic Consortium for Genetic and Newborn Screening Services | title = Understanding Genetics: A New York, Mid-Atlantic Guide for Patients and Health Professionals. | location = Washington (DC) | publisher = Genetic Alliance | date = July 2009 | chapter = APPENDIX E, INHERITANCE PATTERNS | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK115561/}}</ref> The diseases that follow a single-gene inheritance pattern are relatively rare but affect millions of individuals.<ref name="Alliance_2009" /> This can be represented through the [[Mendelian inheritance|Mendelian inheritance patterns]]: <ref name="Alliance_2009" /><ref name="Basta_2025">{{cite book | vauthors = Basta M, Pandya AM | chapter = Genetics, X-Linked Inheritance |date=2025 | title = StatPearls | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK557383/ |access-date=2025-04-05 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491315 }}</ref> [[File:X-linked dominant.svg|thumb|X-linked dominant inheritance patterns, differing between maternal and paternal origin, on offspring]]
* [[Autosomal dominant]]: Where at least one affected parent passes the mutation, and the condition appears in every generation.<ref name="Alliance_2009" /> Examples include [[Huntington's disease]], [[achondroplasia]], and [[neurofibromatosis]].<ref name="Alliance_2009" />
[[File:X-linked recessive (2).svg|thumb|X-linked recessive inheritance patterns, differing between maternal and paternal origin, on offspring]]
* [[Autosomal recessive]]: Both parents are carriers of the mutation (though it may not appear in every generation). The disorder manifests only when both copies of the inherited gene are mutated.<ref name="Alliance_2009" /> Examples include [[Tay–Sachs disease|tay-Sachs disease]], [[Sickle cell disease|sickle cell anemia]], and [[cystic fibrosis]].<ref name="Alliance_2009" /> * X-linked inheritance: Mutated X chromosomes may be inherited in a dominant or recessive manner. Within [[X-linked recessive inheritance]], males are more frequently affected than females. Since males have only one X chromosome, they will express the disease if that single X carries the mutation. Examples include [[Haemophilia|hemophilia]] and [[fabry disease]].<ref name="Basta_2025" /> In contrast, females, with two X chromosomes, must inherit the mutated gene from both parents for the disorder to manifest. [[X-linked dominant inheritance|X-linked dominant]] diseases can affect both males and females. A father with an X-linked dominant trait may only pass it to his daughters, while a mother can pass the trait to both sons and daughters. An example of this is [[incontinentia pigmenti]].<ref name="Basta_2025" />
[[File:Mitochondrial inheritance.svg|thumb|Mitochondrial inheritance pattern and its implication on offspring from a maternal and paternal origin.]]
* Mitochondrial inheritance: This pattern affects both males and females but is inherited and passed only through the mother.<ref name="Alliance_2009" /> Examples include [[Leber's hereditary optic neuropathy]] and [[Kearns–Sayre syndrome|Kearns-Sayre syndrome]].<ref name="Alliance_2009" />
Given these patterns of inheritance, chromosome studies are often conducted on parents when a child is found to have a chromosomal anomaly. If the parents do not exhibit the abnormality, it was not inherited but may be passed down in subsequent generations.<ref>{{Cite web | title = Genetic Testing (for Parents) | url = https://kidshealth.org/en/parents/genetics.html | access-date = 2025-04-05 | website = kidshealth.org | language = english }}</ref>
Chromosomal abnormalities can also arise from [[De novo mutation|de novo mutations]] within an individual.<ref>{{cite journal | vauthors = Liu Y, Shen J, Yang R, Zhang Y, Jia L, Guan Y | veditors = Bevilacqua A | title = The Relationship between Human Embryo Parameters and De Novo Chromosomal Abnormalities in Preimplantation Genetic Testing Cycles | journal = International Journal of Endocrinology | volume = 2022 | article-number = 9707081 | date = 2022-03-19 | pmid = 35345425 | pmc = 8957472 | doi = 10.1155/2022/9707081 | doi-access = free }}</ref> De novo mutations are spontaneous, [[Somatic mutation|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.<ref name="Mohiuddin_2022">{{cite journal | vauthors = Mohiuddin M, Kooy RF, Pearson CE | title = ''De novo'' mutations, genetic mosaicism and human disease | journal = Frontiers in Genetics | volume = 13 | article-number = 983668 | date = 2022-09-26 | pmid = 36226191 | pmc = 9550265 | doi = 10.3389/fgene.2022.983668 | language = English | doi-access = free }}</ref> 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.<ref name="AcunaHidalgo_2016">{{cite journal | vauthors = Acuna-Hidalgo R, Veltman JA, Hoischen A | title = New insights into the generation and role of de novo mutations in health and disease | journal = Genome Biology | volume = 17 | issue = 1 | article-number = 241 | date = November 2016 | pmid = 27894357 | pmc = 5125044 | doi = 10.1186/s13059-016-1110-1 | doi-access = free }}</ref> Approximately 7% of de novo mutations are present as high-level [[Mosaicism|mosaic mutations]].<ref name="AcunaHidalgo_2016" /> [[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 [[Fertilisation|fertilized]] egg.<ref name="Queremel_2025" /><ref name="AcunaHidalgo_2016" /> 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.<ref name="Mohiuddin_2022" /> [[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.<ref name="Queremel_2025" /> An example of a chromosomal abnormality resulting from genetic mosaicism is [[Turner syndrome]].<ref name="Queremel_2025" />
==Acquired chromosome abnormalities== Acquired chromosomal abnormalities represent genetic alterations that manifest during an individual's lifetime, as opposed to being inherited from their parents.<ref name="McFadden_1997" /> These modifications predominantly occur within somatic cells and are characterized by their non-heritable nature.<ref name="McFadden_1997" /> Typically, they arise from mutations that transpire during the process of DNA replication or as a consequence of exposure to various environmental factors.<ref name="McGranahan_2012">{{cite journal | vauthors = McGranahan N, Burrell RA, Endesfelder D, Novelli MR, Swanton C | title = Cancer chromosomal instability: therapeutic and diagnostic challenges | journal = EMBO Reports | volume = 13 | issue = 6 | pages = 528–538 | date = June 2012 | pmid = 22595889 | pmc = 3367245 | doi = 10.1038/embor.2012.61 }}</ref> 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.<ref name="McGranahan_2012" />
The development of chromosomal abnormalities and malignancies can be attributed to environmental exposures or may occur spontaneously during DNA replication.<ref name="McGranahan_2012" /><ref name="Brown_2002">{{cite book | vauthors = Brown TA | chapter = Mutation, Repair and Recombination |date=2002 | title = Genomes | edition = 2nd | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK21114/ |access-date=2025-03-31 |publisher=Wiley-Liss |language=en}}</ref> Spontaneous replication errors typically occur due to DNA polymerase synthesizing new [[Polynucleotide synthetase|polynucleotides]] while evading proofreading functions, leading to mismatches in base pairing.<ref name="Brown_2002" /> Throughout a human's lifetime, individuals may encounter mutagens (which are agents that induce mutations) that lead to chromosomal mutations. These mutations arise when a mutagen interacts with parental DNA, typically affecting one strand, resulting in structural alterations that hinder the successful base pairing with the modified nucleotide.<ref name="Brown_2002" /> Consequently, daughter molecules inherit these mutations, which may further accumulate additional damage, subsequently being passed down to the next generations of cells.<ref name="citea088a1a5">{{Cite web | title = Inherited Mutations and Cancer | url = https://www.facingourrisk.org/info/hereditary-cancer-and-genetic-testing/hereditary-cancer/inherited-mutations-and-cancer | access-date = 2025-03-31 | website = Inherited Mutations and Cancer | language = en }}</ref> [[Mutagen|Mutagens]] can be classified as physical, chemical, or biological:
* Chemical: Common chemical mutagens include [[Nucleic acid analogue|base analogs]] (molecules that resemble nitrogenous bases), [[Deamination|deaminating agents]] (which remove amino groups), [[Alkylation|alkylating agents]], and [[Intercalation (biochemistry)|intercalating agents]].<ref name="Brown_2002" /> * Physical: The most prevalent sources of physical mutagens are exposure to UV radiation, which induces [[dimerization]] of adjacent pyrimidine bases, and ionizing radiation, which typically causes [[Point mutation|point mutations]], [[Insertion mutation|insertions]], or [[Deletion (genetics)|deletions]].<ref name="Brown_2002" /> Heat can also function as a mutagen by promoting the cleavage of the [[Glycosidic bond|β-N-glycosidic bond]], which connects the base to the sugar part of the nucleotide, through water-induced processes.<ref name="Brown_2002" /> * Biological: Biological mutagens are introduced through exposure to viruses, bacteria, and/or [[Transposable element|transposons]] and insertion sequences (IS).<ref name="Kapali_2023">{{Cite web | vauthors = Kapali D | title = Mutagens- Definition, Types (Physical, Chemical, Biological) | date = 2023-08-03 | url = https://microbenotes.com/mutagens-definition-types-examples/ | access-date = 2025-03-31 | website = microbenotes.com | language = en-US }}</ref> 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.<ref name="Kapali_2023" />
Sporadic cancers are those that develop due to mutations that are not inherited; in these cases, normal cells gradually accumulate mutations and cellular damage.<ref name="citea088a1a5" /> Most cancers, if not all, could cause chromosome abnormalities,<ref>{{cite web | title = Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers | url = http://atlasgeneticsoncology.org/Educ/Hempat_e.html | website = atlasgeneticsoncology.org | access-date = 9 May 2018 | url-status = live | archive-url = http://archive.wikiwix.com/cache/20150128231155/http://atlasgeneticsoncology.org/Educ/Hempat_e.html | archive-date = 28 January 2015 }}</ref> 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" <ref>{{cite web | title = Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer | url = https://www.cancer.gov/research/resources | url-status = live | archive-url = http://archive.wikiwix.com/cache/20160529012710/http://cgap.nci.nih.gov/Chromosomes/Mitelman | archive-date = 2016-05-29 }}</ref> and the [[Atlas of Genetics and Cytogenetics in Oncology and Haematology]],<ref>{{cite web | title = Atlas of Genetics and Cytogenetics in Oncology and Haematology | url = http://Atlasgeneticsoncology.org | work = atlasgeneticsoncology.org | url-status = live | archive-url = http://archive.wikiwix.com/cache/20110223164445/http://atlasgeneticsoncology.org/ | archive-date = 2011-02-23 }}</ref>). Approximately 90% of cancers exhibit [[Chromosome instability|chromosomal instability (CIN)]], characterized by the frequent gain or loss of entire chromosome segments.<ref name="Kou_2020">{{cite journal | vauthors = Kou F, Wu L, Ren X, Yang L | title = Chromosome Abnormalities: New Insights into Their Clinical Significance in Cancer | journal = Molecular Therapy Oncolytics | volume = 17 | pages = 562–570 | date = June 2020 | pmid = 32637574 | pmc = 7321812 | doi = 10.1016/j.omto.2020.05.010 }}</ref> This phenomenon contributes to tumor aneuploidy and intra-tumor heterogeneity, which are commonly observed in most human cancers.<ref name="McGranahan_2012" /><ref name="Kou_2020" /> For instance, certain consistent chromosomal abnormalities can turn normal cells into a leukemic cell such as the translocation of a gene, resulting in its inappropriate expression.<ref>{{cite journal | vauthors = Chaganti RS, Nanjangud G, Schmidt H, Teruya-Feldstein J | title = Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance | journal = Seminars in Hematology | volume = 37 | issue = 4 | pages = 396–411 | date = October 2000 | pmid = 11071361 | doi = 10.1016/s0037-1963(00)90019-2 }}</ref>
==DNA damage during spermatogenesis==
[[DNA damage (naturally occurring)|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).<ref>{{Cite journal | vauthors = Baarends W | title = DNA repair mechanisms and gametogenesis | journal = Reproduction | volume = 121 | issue = 1 | pages = 31–39 | date = 2001-01-01 | doi = 10.1530/reprod/121.1.31 | pmid = 11226027 | url = https://rep.bioscientifica.com/doi/10.1530/reprod/121.1.31 | language = en | issn = 1470-1626 | hdl = 1765/9599 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Talibova G, Bilmez Y, Ozturk S | title = DNA double-strand break repair in male germ cells during spermatogenesis and its association with male infertility development | journal = DNA Repair | volume = 118 | date = October 2022 | pmid = 35963140 | doi = 10.1016/j.dnarep.2022.103386 | article-number = 103386 }}</ref> 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.<ref>{{cite journal | vauthors = Marchetti F, Bishop J, Gingerich J, Wyrobek AJ | title = Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair | journal = Scientific Reports | volume = 5 | issue = 1 | article-number = 7689 | date = January 2015 | pmid = 25567288 | pmc = 4286742 | doi = 10.1038/srep07689 | bibcode = 2015NatSR...5.7689M }}</ref> 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.<ref>{{cite journal | vauthors = Cao Y, Wang S, Qin Z, Xiong Q, Liu J, Li W, Li L, Ao F, Wei Z, Wang L | title = Male germ cells with Bag5 deficiency show reduced spermiogenesis and exchange of basic nuclear proteins | journal = Cellular and Molecular Life Sciences | volume = 82 | issue = 1 | article-number = 92 | date = February 2025 | pmid = 39992433 | pmc = 11850669 | doi = 10.1007/s00018-025-05591-2 }}</ref> 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.<ref>{{cite journal | vauthors = Wang Y, Fu X, Li H | title = Mechanisms of oxidative stress-induced sperm dysfunction | journal = Frontiers in Endocrinology | volume = 16 | article-number = 1520835 | date = 2025-02-05 | pmid = 39974821 | pmc = 11835670 | doi = 10.3389/fendo.2025.1520835 | doi-access = free }}</ref>
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.<ref>{{cite journal | vauthors = Sharma P, Kaushal N, Saleth LR, Ghavami S, Dhingra S, Kaur P | title = Oxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease| volume = 1869 | issue = 6 | article-number = 166742 | date = August 2023 | pmid = 37146914 | doi = 10.1016/j.bbadis.2023.166742 }}</ref> If these sperm fertilize an egg, the oocyte's repair mechanisms may attempt to fix the damage.<ref>{{cite journal | vauthors = Li N, Wang H, Zou S, Yu X, Li J | title = Perspective in the Mechanisms for Repairing Sperm DNA Damage | journal = Reproductive Sciences | volume = 32 | issue = 1 | pages = 41–51 | date = January 2025 | pmid = 39333437 | pmc = 11729216 | doi = 10.1007/s43032-024-01714-5 }}</ref>
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]].<ref>{{cite journal | vauthors = Marchetti F, Essers J, Kanaar R, Wyrobek AJ | title = Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 45 | pages = 17725–17729 | date = November 2007 | pmid = 17978187 | pmc = 2077046 | doi = 10.1073/pnas.0705257104 | doi-access = free | bibcode = 2007PNAS..10417725M }}</ref> 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.<ref>{{cite journal | vauthors = Deans AJ, West SC | title = DNA interstrand crosslink repair and cancer | journal = Nature Reviews. Cancer | volume = 11 | issue = 7 | pages = 467–480 | date = June 2011 | pmid = 21701511 | pmc = 3560328 | doi = 10.1038/nrc3088 | bibcode = 2011NatRC..11..467D }}</ref>
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.<ref>{{cite journal | vauthors = Zini A, Libman J | title = Sperm DNA damage: clinical significance in the era of assisted reproduction | journal = CMAJ | volume = 175 | issue = 5 | pages = 495–500 | date = August 2006 | pmid = 16940270 | pmc = 1550758 | doi = 10.1503/cmaj.060218 }}</ref>
== Detection == Chromosomal abnormalities can be detected at either postnatal testing or prenatal screening, which includes prenatal diagnosis.<ref>{{cite journal | vauthors = Fonda Allen J, Stoll K, Bernhardt BA | title = Pre- and post-test genetic counseling for chromosomal and Mendelian disorders | journal = Seminars in Perinatology | volume = 40 | issue = 1 | pages = 44–55 | date = February 2016 | pmid = 26718445 | pmc = 4826755 | doi = 10.1053/j.semperi.2015.11.007 | series = The Changing Paradigm of Perinatal screening for Birth Defects }}</ref> Early detection is crucial for enabling parents to assess their upcoming pregnancy options.<ref name="Hixson_2015">{{cite journal | vauthors = Hixson L, Goel S, Schuber P, Faltas V, Lee J, Narayakkadan A, Leung H, Osborne J | title = An Overview on Prenatal Screening for Chromosomal Aberrations | journal = Journal of Laboratory Automation | volume = 20 | issue = 5 | pages = 562–573 | date = October 2015 | pmid = 25587000 | doi = 10.1177/2211068214564595 | language = English | doi-access = free }}</ref>
Common techniques used to detect diseases resulting from chromosomal abnormalities:
* [[Karyotype|Karyotyping]] * [[Fluorescence in situ hybridization|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.<ref name="Queremel_2025" /> The samples used to obtain results from fetal karyotyping can be acquired through various sampling techniques. Amongst the aneuploidy testings, those which use [[amniotic fluid]] is preferred due its benefit of having high sensitivity with relatively low risks.<ref name="Hixson_2015" />
For increased resolution of screening, Chromosomal Microarray Analysis (CMA) can be used which is based on [[comparative genomic hybridization]] (CGH) to identify copy number variations (CNVs). This alternative method to karyotyping reduces result uncertainty through its use of invasive fetal cell collection technique.<ref name="Hixson_2015" />
FISH technique detects chromosomal abnormalities through labeling of the chromosome by fluorescence using specialized probes. It is important that these probes are validated before use as they are carefully regulated by the [[Food and Drug Administration|Food and Drug Administration (FDA)]].<ref name="Hixson_2015" />
FISH is a technique used for the treatment of specific cases such as [[Multiple myeloma|Multiple myeloma (MM)]] and can be used to analyze bone marrow samples to identify changes in chromosomes at a single-cell level.<ref name="Locher_2023">{{cite journal | vauthors = Locher M, Jukic E, Vogi V, Keller MA, Kröll T, Schwendinger S, Oberhuber K, Verdorfer I, Mühlegger BE, Witsch-Baumgartner M, Nachbaur D, Willenbacher W, Gunsilius E, Wolf D, Zschocke J, Steiner N | title = Amp(1q) and tetraploidy are commonly acquired chromosomal abnormalities in relapsed multiple myeloma | journal = European Journal of Haematology | volume = 110 | issue = 3 | pages = 296–304 | date = March 2023 | pmid = 36433728 | pmc = 10107198 | doi = 10.1111/ejh.13905 }}</ref> 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.<ref name="Locher_2023" />
Spectral Karyotyping (SKY) is a recent technology developed from the FISH technique that colors each human chromosome in a different color for identification in analysis.<ref name="Imataka_2012">{{cite journal | vauthors = Imataka G, Arisaka O | title = Chromosome analysis using spectral karyotyping (SKY) | journal = Cell Biochemistry and Biophysics | volume = 62 | issue = 1 | pages = 13–17 | date = January 2012 | pmid = 21948110 | pmc = 3254861 | doi = 10.1007/s12013-011-9285-2 }}</ref> Through the use of [[Fluorophore|fluorescent dyes]] such as Cy5, Texas red and spectrum green, 24 distinguishable colors can be generated using imaging spectroscopy.<ref name="Imataka_2012" />
Depending on the information one wants to obtain, different techniques and samples are needed.{{citation needed|date=April 2023}} * 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 [[Preimplantation genetic diagnosis|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==
<gallery mode="packed" heights="340"> 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.<ref>{{cite journal | vauthors = Warrender JD, Moorman AV, Lord P | title = A fully computational and reasonable representation for karyotypes | journal = Bioinformatics | volume = 35 | issue = 24 | pages = 5264–5270 | date = December 2019 | pmid = 31228194 | pmc = 6954653 | doi = 10.1093/bioinformatics/btz440 }}<br />- "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)"</ref> File:Human karyotype with bands and sub-bands.png|Human [[karyotype]] with annotated [[Locus (genetics)|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 chromosome|homologous]] [[autosomal]] chromosome pairs, both the female (XX) and male (XY) versions of the two [[sex chromosome]]s, as well as the [[human mitochondrial genetics|mitochondrial genome]] (at bottom left). </gallery> {{further|Karyotype}}
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.<ref>{{cite web | title = ISCN Symbols and Abbreviated Terms | url = https://www.coriell.org/0/sections/support/global/iscn_help.aspx?PgId=263 | website = Coriell Institute for Medical Research | access-date = 2022-10-27 }}</ref>
== See also == * [[Aneuploidy]] * [[Chromosome segregation]] * [[Genetic disorder]] ** [[List of genetic disorders]] * [[Gene therapy]] * [[Nondisjunction]] * [[Obstetrical complications]] {{clear}}
== References == {{reflist}}
== External links == * {{MeshName|Chromosome+disorders}}
{{Chromosomal abnormalities}} {{Mutation}}
{{Authority control}}
[[Category:Chromosomal abnormalities]] [[Category:Cytogenetics]] [[Category:Genetics concepts]]