Chromosome abnormality

A chromosomal disorder, anomaly, aberration, or mutation is a missing, extra, or irregular portion of chromosomal DNA.[1] It can be from a typical number of chromosomes or a structural abnormality in one or more chromosomes. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene.[2] The term "karyotype" refers to the full set of chromosomes from an individual; this can be compared to a "normal" karyotype for the species via genetic testing. A chromosome anomaly may be detected or confirmed in this manner. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. There are many types of chromosome anomalies. They can be organized into two basic groups, numerical and structural anomalies.

The three major single-chromosome mutations: deletion (1), duplication (2) and inversion (3).
The two major two-chromosome mutations: insertion (1) and Translocation (2).

Numerical disorders

This is called aneuploidy (an abnormal number of chromosomes), and occurs when an individual either is missing a chromosome from a pair (monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.).[3]

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. Having an extra copy of this chromosome means that individuals have three copies of each of its genes instead of two, making it difficult for cells to properly control how much protein is made. Producing too much or too little protein can have serious consequences. Genes on chromosome 21 that specifically contribute to the various symptoms of Down syndrome are now being identified. The frequency of Trisomy 21 has been determined to be a function of advanced maternal age.

An example of monosomy 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.[4] In particular, risk of aneuploidy is increased by tobacco smoking,[5][6] and occupational exposure to benzene,[7] insecticides,[8][9] and perfluorinated compounds.[10] Increased aneuploidy is often associated with increased DNA damage in spermatozoa.

Structural abnormalities

When the chromosome's structure is altered, this can take several forms:[11]

  • Deletions: A portion of the chromosome is missing or deleted. 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.
  • Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material. 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.
  • Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocations:
  • Inversions: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted.
  • Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
  • Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.
  • Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.

Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.


Most chromosome abnormalities occur as an accident in the egg cell or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in Mosaicism (where some cells have the anomaly and some do not). Chromosome anomalies can be inherited from a parent or be "de novo". This is why chromosome studies are often performed on parents when a child is found to have an anomaly. If the parents do not possess the abnormality it was not initially inherited; however it may be transmitted to subsequent generations.

Acquired chromosome abnormalities

Most cancers, if not all, could cause chromosome abnormalities,[12] 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" [13] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology,[14]). Furthermore, certain consistent chromosomal abnormalities can turn normal cells into a leukemic cell such as the translocation of a gene, resulting in its inappropriate expression.[15]

DNA damage during spermatogenesis

During the mitotic and meiotic cell divisions of mammalian gametogenesis, DNA repair is effective at removing DNA damages.[16] However, in spermatogenesis the ability to repair DNA damages decreases substantially in the latter part of the process as haploid spermatids undergo major nuclear chromatin remodeling into highly compacted sperm nuclei. As reviewed by Marchetti et al.,[17] the last few weeks of sperm development before fertilization are highly susceptible to the accumulation of sperm DNA damage. Such sperm DNA damage can be transmitted unrepaired into the egg where it is subject to removal by the maternal repair machinery. However, errors in maternal DNA repair of sperm DNA damage can result in zygotes with chromosomal structural aberrations.

Melphalan is a bifunctional alkylating agent frequently used in chemotherapy. Meiotic inter-strand DNA damages caused by melphalan can escape paternal repair and cause chromosomal aberrations in the zygote by maternal misrepair.[17] Thus both pre- and post-fertilization DNA repair appear to be important in avoiding chromosome abnormalities and assuring the genome integrity of the conceptus.


Depending on the information one wants to obtain, different techniques and samples are needed.

See also


  1. NHGRI. 2006. Chromosome Abnormalities Archived 2006-09-25 at the Wayback Machine
  2. Rieger, R.; Michaelis, A.; Green, M.M. (1968). "Mutation". A glossary of genetics and cytogenetics: Classical and molecular. New York: Springer-Verlag. ISBN 9780387076683.
  3. Santaguida, Stefano; Amon, Angelika (2015-08-01). "Short- and long-term effects of chromosome mis-segregation and aneuploidy". Nature Reviews Molecular Cell Biology. 16 (8): 473–485. doi:10.1038/nrm4025. hdl:1721.1/117201. ISSN 1471-0080. PMID 26204159.
  4. Templado C, Uroz L, Estop A (2013). "New insights on the origin and relevance of aneuploidy in human spermatozoa". Mol. Hum. Reprod. 19 (10): 634–43. doi:10.1093/molehr/gat039. PMID 23720770.
  5. Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R (2001). "Cigarette smoking and aneuploidy in human sperm". Mol. Reprod. Dev. 59 (4): 417–21. doi:10.1002/mrd.1048. PMID 11468778.
  6. Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ (1998). "Smoking cigarettes is associated with increased sperm disomy in teenage men". Fertil. Steril. 70 (4): 715–23. doi:10.1016/S0015-0282(98)00261-1. PMID 9797104.
  7. Xing C, Marchetti F, Li G, Weldon RH, Kurtovich E, Young S, Schmid TE, Zhang L, Rappaport S, Waidyanatha S, Wyrobek AJ, Eskenazi B (2010). "Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy". Environ. Health Perspect. 118 (6): 833–9. doi:10.1289/ehp.0901531. PMC 2898861. PMID 20418200.
  8. Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X (2004). "Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate". Toxicology. 203 (1–3): 49–60. doi:10.1016/j.tox.2004.05.018. PMID 15363581.
  9. Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X (2005). "Genotoxic effects on spermatozoa of carbaryl-exposed workers". Toxicol. Sci. 85 (1): 615–23. doi:10.1093/toxsci/kfi066. PMID 15615886.
  10. Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P (2014). "Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds". Andrologia. 47 (9): 1012–9. doi:10.1111/and.12371. PMID 25382683.
  11. "Chromosome Abnormalities". Archived from the original on 14 August 2006. Retrieved 9 May 2018.
  12. "Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers". Archived from the original on 28 January 2015. Retrieved 9 May 2018.
  13. "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-29.
  14. "Atlas of Genetics and Cytogenetics in Oncology and Haematology". Archived from the original on 2011-02-23.
  15. Chaganti, R. S.; Nanjangud, G.; Schmidt, H.; Teruya-Feldstein, J. (October 2000). "Recurring chromosomal abnormalities in non-Hodgkin's lymphoma: biologic and clinical significance". Seminars in Hematology. 37 (4): 396–411. doi:10.1016/s0037-1963(00)90019-2. ISSN 0037-1963. PMID 11071361.
  16. Baarends WM, van der Laan R, Grootegoed JA (2001). "DNA repair mechanisms and gametogenesis". Reproduction. 121 (1): 31–9. doi:10.1530/reprod/121.1.31. PMID 11226027.
  17. Marchetti F, Bishop J, Gingerich J, Wyrobek AJ (2015). "Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair". Sci Rep. 5: 7689. doi:10.1038/srep07689. PMC 4286742. PMID 25567288.
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