Ingenetics, adeletion (also calledgene deletion,deficiency, ordeletion mutation) (sign:Δ) is amutation (a genetic aberration) in which a part of achromosome or a sequence ofDNA is left out during DNA replication. Any number ofnucleotides can be deleted, from a singlebase to an entire piece of chromosome.[1] Somechromosomes have fragile spots where breaks occur, which result in thedeletion of a part of the chromosome. The breaks can be induced by heat, viruses, radiation, or chemical reactions. When achromosome breaks, if a part of it is deleted or lost, the missing piece of chromosome is referred to as a deletion or a deficiency.[2]
Forsynapsis to occur between a chromosome with a large intercalary deficiency and a normal complete homolog, the unpaired region of the normal homolog must loop out of the linear structure into adeletion orcompensation loop.
The smallest single base deletion mutations occur by a singlebase flipping in the template DNA, followed by template DNA strand slippage, within the DNA polymerase active site.[3][4][5]
Deletions can be caused by errors inchromosomal crossover duringmeiosis, which causes several seriousgenetic diseases. Deletions that do not occur in multiples of three bases can cause aframeshift by changing the 3-nucleotide protein reading frame of the genetic sequence. Deletions are representative ofeukaryotic organisms, including humans and not inprokaryotic organisms, such as bacteria.
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.[6]Humankaryotype with annotated bands and sub-bands as used for the nomenclature of chromosome abnormalities. It shows dark and white regions as seen onG banding. Each row is vertically aligned atcentromere level. It shows 22homologousautosomal chromosome pairs, both the female (XX) and male (XY) versions of the twosex chromosomes, as well as themitochondrial genome (at bottom left).
TheInternational System for Human Cytogenomic Nomenclature (ISCN) is an international standard forhuman chromosomenomenclature, 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, anddel for deletions of parts of a chromosome.[7]
Small deletions are less likely to be fatal; large deletions are usually fatal – there are always variations based on which genes are lost. Some medium-sized deletions lead to recognizable human disorders, e.g.Williams syndrome.
Deletion of a number of pairs that is not evenly divisible by three will lead to aframeshift mutation, causing all of thecodons occurring after the deletion to be read incorrectly duringtranslation, producing a severely altered and potentially nonfunctionalprotein. In contrast, a deletion that is evenly divisible by three is called anin-frame deletion.[8]
Deletions are responsible for an array of genetic disorders, including some cases of maleinfertility, two thirds of cases ofDuchenne muscular dystrophy,[1] and two thirds of cases ofcystic fibrosis (those caused byΔF508).[9] Deletion of part of the short arm of chromosome 5 results inCri du chat syndrome.[1] Deletions in theSMN-encoding gene causespinal muscular atrophy, the most common genetic cause of infant death.
Microdeletions are associated with many different conditions, including Angelman syndrome, Prader-Willi syndrome, and DiGeorge syndrome.[10] Some syndromes, including Angelman syndrome and Prader-Willi syndrome, are associated with both microdeletions and genomic imprinting, meaning that same microdeletion can cause two different syndromes depending on which parent the deletion came from.[11]
Recent work suggests that some deletions of highly conserved sequences (CONDELs) may be responsible for the evolutionary differences present among closely related species. Such deletions in humans, referred to ashCONDELs, may be responsible for the anatomical and behavioral differences between humans,chimpanzees and other varieties of mammals likeape ormonkeys.[12]
Recent comprehensive patient-level classification and quantification of driver events inTCGA cohorts revealed that there are on average 12 driver events per tumor, of which 2.1 are deletions oftumor suppressors.[13]
The introduction of molecular techniques in conjunction with classical cytogenetic methods has in recent years greatly improved the diagnostic potential for chromosomal abnormalities. In particular, microarray-comparative genomic hybridization (CGH) based on the use of BAC clones promises a sensitive strategy for the detection of DNA copy-number changes on a genome-wide scale. The resolution of detection could be as high as >30,000 "bands" and the size of chromosomal deletion detected could as small as 5–20 kb in length.[14] Other computation methods were selected to discoverDNA sequencing deletion errors such asend-sequence profiling.[15][16]
In the yeastSaccharomyces cerevisiae, the nuclear genesRad51p,Rad52p andRad59p encode proteins that are necessary for recombinational repair and are employed in the repair ofdouble strand breaks inmitochondrial DNA.[17] Loss of these proteins decreases the rate of spontaneous DNA deletion events in mitochondria.[17] This finding implies that the repair of DNA double-strand breaks by homologous recombination is a step in the formation of mitochondrial DNA deletions.
^abcLewis, R. (2004).Human Genetics: Concepts and Applications (6th ed.). McGraw Hill.ISBN978-0-07-295174-5.
^Klug, William S. (2015).Concepts of genetics. Michael R. Cummings, Charlotte A. Spencer, Michael Angelo Palladino (Eleventh ed.). Boston.ISBN978-0-321-94891-5.OCLC880404074.{{cite book}}: CS1 maint: location missing publisher (link)
^Banavali, Nilesh K. (2013). "Analyzing the Relationship between Single Base Flipping and Strand Slippage near DNA Duplex Termini".The Journal of Physical Chemistry B.117 (46):14320–14328.doi:10.1021/jp408957c.PMID24206351.
^Mitchell, Richard Sheppard; Kumar, Vinay; Robbins, Stanley L.; Abbas, Abul K.; Fausto, Nelson (2007).Robbins basic pathology. Saunders/Elsevier.ISBN978-1-4160-2973-1.
^abIvanetich, K. M.; Lucas, S.; Marsh, J. A.; Ziman, M. R.; Katz, I. D.; Bradshaw, J. J. (1978). "Organic compounds. Their interaction with and degradation of hepatic microsomal drug-metabolizing enzymes in vitro".Drug Metabolism and Disposition: The Biological Fate of Chemicals.6 (3):218–225.doi:10.1016/S0090-9556(25)06283-X.PMID26540.
