In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome.[1] Some chromosomes have fragile spots where breaks occur which result in the deletion of a part of chromosome. The breaks can be induced by heat, viruses, radiations, chemicals. When a chromosome breaks, a part of it is deleted or lost, the missing piece of chromosome is referred to as deletion or a deficiency.[2]
Deletion on a chromosome
For synapsis 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 a deletion or compensation loop.
The smallest single base deletion mutations occur by a single base 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 in chromosomal crossover during meiosis, which causes several serious genetic diseases. Deletions that do not occur in multiples of three bases can cause a frameshift by changing the 3-nucleotide protein reading frame of the genetic sequence. Deletions are representative of eukaryotic organisms, including humans and not in prokaryotic organisms, such as bacteria.
Terminal deletion – a deletion that occurs towards the end of a chromosome.
Intercalary/interstitial deletion – a deletion that occurs from the interior of a chromosome.
Microdeletion – a relatively small amount of deletion (up to 5Mb that could include a dozen genes).
Micro-deletion is usually found in children with physical abnormalities. A large amount of deletion would result in immediate abortion (miscarriage).
Nomenclature
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]
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 homologousautosomal 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 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, and del for deletions of parts of a chromosome.[7]
Effects
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 a frameshift mutation, causing all of the codons occurring after the deletion to be read incorrectly during translation, producing a severely altered and potentially nonfunctional protein. In contrast, a deletion that is evenly divisible by three is called an in-frame deletion.[8]
Deletions are responsible for an array of genetic disorders, including some cases of male infertility, two thirds of cases of Duchenne muscular dystrophy,[1] and two thirds of cases of cystic fibrosis (those caused by ΔF508).[9] Deletion of part of the short arm of chromosome 5 results in Cri du chat syndrome.[1] Deletions in the SMN-encoding gene cause spinal 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 as hCONDELs, may be responsible for the anatomical and behavioral differences between humans, chimpanzees and other varieties of mammals like ape or monkeys.[12]
Recent comprehensive patient-level classification and quantification of driver events in TCGA cohorts revealed that there are on average 12 driver events per tumor, of which 2.1 are deletions of tumor suppressors.[13]
Detection
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 discover DNA sequencing deletion errors such as end-sequence profiling.[15][16]
Mitochondrial DNA deletions
In the yeast Saccharomyces cerevisiae, the nuclear genes Rad51p, Rad52p and Rad59p encode proteins that are necessary for recombinational repair and are employed in the repair of double strand breaks in mitochondrial 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. ISBN978-0072951745.
^Klug, William S. (2015). Concepts of genetics. Michael R. Cummings, Charlotte A. Spencer, Michael Angelo Palladino (Eleventh ed.). Boston. ISBN978-0-321-94891-5. OCLC 880404074.
^Banavali, Nilesh K. (2013). "Partial Base Flipping is Sufficient for Strand Slippage near DNA Duplex Termini". Journal of the American Chemical Society. 135 (22): 8274–8282. doi:10.1021/ja401573j. PMID 23692220.
^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. PMID 24206351.
^Manjari, Swati R.; Pata, Janice D.; Banavali, Nilesh K. (2014). "Cytosine Unstacking and Strand Slippage at an Insertion–Deletion Mutation Sequence in an Overhang-Containing DNA Duplex". Biochemistry. 53 (23): 3807–3816. doi:10.1021/bi500189g. PMC4063443. PMID 24854722.
^Warrender JD, Moorman AV, Lord P (2019). "A fully computational and reasonable representation for karyotypes". Bioinformatics. 35 (24): 5264–5270. doi:10.1093/bioinformatics/btz440. PMC6954653. PMID 31228194.{{cite journal}}: CS1 maint: multiple names: authors list (link) - "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/)"
^"ISCN Symbols and Abbreviated Terms". Coriell Institute for Medical Research. Retrieved 2022-10-27.
^LSDB — Controlled vocabulary terms 2011-10-06 at the Wayback Machine at The GEN2PHEN Knowledge Centre. Posted Fri, 08/01/2010.
^Mitchell, Richard Sheppard; Kumar, Vinay; Robbins, Stanley L.; Abbas, Abul K.; Fausto, Nelson (2007). Robbins basic pathology. Saunders/Elsevier. ISBN978-1-4160-2973-1.
^Srour, Myriam; Shevell, Michael (2015-01-01), Rosenberg, Roger N.; Pascual, Juan M. (eds.), "Chapter 14 - Global Developmental Delay and Intellectual Disability", Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition), Boston: Academic Press, pp. 151–161, ISBN978-0-12-410529-4, retrieved 2022-01-07
^Kalsner, Louisa; Chamberlain, Stormy J. (April 22, 2015). "Prader-Willi, Angelman, and 15q11-q13 duplication syndromes". Pediatric Clinics of North America. 62 (3): 587–606. doi:10.1016/j.pcl.2015.03.004. ISSN 0031-3955. PMC4449422. PMID 26022164.
^McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT, Wenger AM, Bejerano G, Kingsley DM (March 2011). "Human-specific loss of regulatory DNA and the evolution of human-specific traits". Nature. 471 (7337): 216–9. Bibcode:2011Natur.471..216M. doi:10.1038/nature09774. PMC3071156. PMID 21390129.
^Vyatkin, Alexey D.; Otnyukov, Danila V.; Leonov, Sergey V.; Belikov, Aleksey V. (14 January 2022). "Comprehensive patient-level classification and quantification of driver events in TCGA PanCanAtlas cohorts". PLOS Genetics. 18 (1): e1009996. doi:10.1371/journal.pgen.1009996. PMC8759692. PMID 35030162.
^Ren, H (May 2005). "BAC-based PCR fragment microarray: high-resolution detection of chromosomal deletion and duplication breakpoints". Human Mutation. 25 (5): 476–482. doi:10.1002/humu.20164. PMID 15832308. S2CID 28030180.
^Shmilovici, A.; Ben-Gal, I. (2007). "Using a VOM Model for Reconstructing Potential Coding Regions in EST Sequences" (PDF). Journal of Computational Statistics. 22 (1): 49–69. doi:10.1007/s00180-007-0021-8. S2CID 2737235.
^Volik, S.; Zhao, S.; Chin, K.; Brebner, J. H.; Herndon, D. R.; Tao, Q.; Kowbel, D.; Huang, G.; Lapuk, A.; Kuo, W.-L.; Magrane, G.; de Jong, P.; Gray, J. W.; Collins, C. (4 June 2003). "End-sequence profiling: Sequence-based analysis of aberrant genomes". Proceedings of the National Academy of Sciences. 100 (13): 7696–7701. Bibcode:2003PNAS..100.7696V. doi:10.1073/pnas.1232418100. PMC164650. PMID 12788976.
^ abStein A, Kalifa L, Sia EA. Members of the RAD52 Epistasis Group Contribute to Mitochondrial Homologous Recombination and Double-Strand Break Repair in Saccharomyces cerevisiae. PLoS Genet. 2015 Nov 5;11(11):e1005664. doi: 10.1371/journal.pgen.1005664. PMID: 26540
Wikimedia Commons has media related to Deletion (genetics).
January 20, 2023
deletion, genetics, genetics, deletion, also, called, gene, deletion, deficiency, deletion, mutation, sign, mutation, genetic, aberration, which, part, chromosome, sequence, left, during, replication, number, nucleotides, deleted, from, single, base, entire, p. In genetics a deletion also called gene deletion deficiency or deletion mutation sign D is a mutation a genetic aberration in which a part of a chromosome or a sequence of DNA is left out during DNA replication Any number of nucleotides can be deleted from a single base to an entire piece of chromosome 1 Some chromosomes have fragile spots where breaks occur which result in the deletion of a part of chromosome The breaks can be induced by heat viruses radiations chemicals When a chromosome breaks a part of it is deleted or lost the missing piece of chromosome is referred to as deletion or a deficiency 2 Deletion on a chromosome For synapsis 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 a deletion or compensation loop The smallest single base deletion mutations occur by a single base 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 in chromosomal crossover during meiosis which causes several serious genetic diseases Deletions that do not occur in multiples of three bases can cause a frameshift by changing the 3 nucleotide protein reading frame of the genetic sequence Deletions are representative of eukaryotic organisms including humans and not in prokaryotic organisms such as bacteria Contents 1 Causes 2 Types 3 Nomenclature 4 Effects 5 Detection 6 Mitochondrial DNA deletions 7 See also 8 ReferencesCauses EditCauses include the following Losses from translocation Chromosomal crossovers within a chromosomal inversion Unequal crossing over Breaking without rejoiningTypes EditTypes of deletion include the following Terminal deletion a deletion that occurs towards the end of a chromosome Intercalary interstitial deletion a deletion that occurs from the interior of a chromosome Microdeletion a relatively small amount of deletion up to 5Mb that could include a dozen genes Micro deletion is usually found in children with physical abnormalities A large amount of deletion would result in immediate abortion miscarriage Nomenclature Edit 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 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 Further information 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 7 Effects EditSmall 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 a frameshift mutation causing all of the codons occurring after the deletion to be read incorrectly during translation producing a severely altered and potentially nonfunctional protein In contrast a deletion that is evenly divisible by three is called an in frame deletion 8 Deletions are responsible for an array of genetic disorders including some cases of male infertility two thirds of cases of Duchenne muscular dystrophy 1 and two thirds of cases of cystic fibrosis those caused by DF508 9 Deletion of part of the short arm of chromosome 5 results in Cri du chat syndrome 1 Deletions in the SMN encoding gene cause spinal 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 as hCONDELs may be responsible for the anatomical and behavioral differences between humans chimpanzees and other varieties of mammals like ape or monkeys 12 Recent comprehensive patient level classification and quantification of driver events in TCGA cohorts revealed that there are on average 12 driver events per tumor of which 2 1 are deletions of tumor suppressors 13 Detection EditThe 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 gt 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 discover DNA sequencing deletion errors such as end sequence profiling 15 16 Mitochondrial DNA deletions EditIn the yeast Saccharomyces cerevisiae the nuclear genes Rad51p Rad52p and Rad59p encode proteins that are necessary for recombinational repair and are employed in the repair of double strand breaks in mitochondrial 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 See also EditIndel Chromosome abnormalities Null allele List of genetic disorders Medical genetics Microdeletion syndrome Chromosomal deletion syndrome Insertion genetics References Edit a b c Lewis R 2004 Human Genetics Concepts and Applications 6th ed McGraw Hill ISBN 978 0072951745 Klug William S 2015 Concepts of genetics Michael R Cummings Charlotte A Spencer Michael Angelo Palladino Eleventh ed Boston ISBN 978 0 321 94891 5 OCLC 880404074 Banavali Nilesh K 2013 Partial Base Flipping is Sufficient for Strand Slippage near DNA Duplex Termini Journal of the American Chemical Society 135 22 8274 8282 doi 10 1021 ja401573j PMID 23692220 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 PMID 24206351 Manjari Swati R Pata Janice D Banavali Nilesh K 2014 Cytosine Unstacking and Strand Slippage at an Insertion Deletion Mutation Sequence in an Overhang Containing DNA Duplex Biochemistry 53 23 3807 3816 doi 10 1021 bi500189g PMC 4063443 PMID 24854722 Warrender JD Moorman AV Lord P 2019 A fully computational and reasonable representation for karyotypes Bioinformatics 35 24 5264 5270 doi 10 1093 bioinformatics btz440 PMC 6954653 PMID 31228194 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link This is an Open Access article distributed under the terms of the Creative Commons Attribution License http creativecommons org licenses by 4 0 ISCN Symbols and Abbreviated Terms Coriell Institute for Medical Research Retrieved 2022 10 27 LSDB Controlled vocabulary terms Archived 2011 10 06 at the Wayback Machine at The GEN2PHEN Knowledge Centre Posted Fri 08 01 2010 Mitchell Richard Sheppard Kumar Vinay Robbins Stanley L Abbas Abul K Fausto Nelson 2007 Robbins basic pathology Saunders Elsevier ISBN 978 1 4160 2973 1 Srour Myriam Shevell Michael 2015 01 01 Rosenberg Roger N Pascual Juan M eds Chapter 14 Global Developmental Delay and Intellectual Disability Rosenberg s Molecular and Genetic Basis of Neurological and Psychiatric Disease Fifth Edition Boston Academic Press pp 151 161 ISBN 978 0 12 410529 4 retrieved 2022 01 07 Kalsner Louisa Chamberlain Stormy J April 22 2015 Prader Willi Angelman and 15q11 q13 duplication syndromes Pediatric Clinics of North America 62 3 587 606 doi 10 1016 j pcl 2015 03 004 ISSN 0031 3955 PMC 4449422 PMID 26022164 McLean CY Reno PL Pollen AA Bassan AI Capellini TD Guenther C Indjeian VB Lim X Menke DB Schaar BT Wenger AM Bejerano G Kingsley DM March 2011 Human specific loss of regulatory DNA and the evolution of human specific traits Nature 471 7337 216 9 Bibcode 2011Natur 471 216M doi 10 1038 nature09774 PMC 3071156 PMID 21390129 Vyatkin Alexey D Otnyukov Danila V Leonov Sergey V Belikov Aleksey V 14 January 2022 Comprehensive patient level classification and quantification of driver events in TCGA PanCanAtlas cohorts PLOS Genetics 18 1 e1009996 doi 10 1371 journal pgen 1009996 PMC 8759692 PMID 35030162 Ren H May 2005 BAC based PCR fragment microarray high resolution detection of chromosomal deletion and duplication breakpoints Human Mutation 25 5 476 482 doi 10 1002 humu 20164 PMID 15832308 S2CID 28030180 Shmilovici A Ben Gal I 2007 Using a VOM Model for Reconstructing Potential Coding Regions in EST Sequences PDF Journal of Computational Statistics 22 1 49 69 doi 10 1007 s00180 007 0021 8 S2CID 2737235 Volik S Zhao S Chin K Brebner J H Herndon D R Tao Q Kowbel D Huang G Lapuk A Kuo W L Magrane G de Jong P Gray J W Collins C 4 June 2003 End sequence profiling Sequence based analysis of aberrant genomes Proceedings of the National Academy of Sciences 100 13 7696 7701 Bibcode 2003PNAS 100 7696V doi 10 1073 pnas 1232418100 PMC 164650 PMID 12788976 a b Stein A Kalifa L Sia EA Members of the RAD52 Epistasis Group Contribute to Mitochondrial Homologous Recombination and Double Strand Break Repair in Saccharomyces cerevisiae PLoS Genet 2015 Nov 5 11 11 e1005664 doi 10 1371 journal pgen 1005664 PMID 26540 Wikimedia Commons has media related to Deletion genetics Retrieved from https en wikipedia org w index php title Deletion genetics amp oldid 1125744937, wikipedia, wiki, book, books, library,
