Global InformationIndel information
Indel (insertion-deletion) is a molecular biology term for an insertion or deletion of bases in the genome of an organism. Indels ≥ 50 bases in length are classified as structural variants.[1][2]
In coding regions of the genome, unless the length of an indel is a multiple of 3, it will produce a frameshift mutation. For example, a common microindel which results in a frameshift causes Bloom syndrome in the Jewish or Japanese population.[3] Indels can be contrasted with a point mutation. An indel inserts or deletes nucleotides from a sequence, while a point mutation is a form of substitution that replaces one of the nucleotides without changing the overall number in the DNA. Indels can also be contrasted with Tandem Base Mutations (TBM), which may result from fundamentally different mechanisms.[4] A TBM is defined as a substitution at adjacent nucleotides (primarily substitutions at two adjacent nucleotides, but substitutions at three adjacent nucleotides have been observed).[5]
Indels, being either insertions, or deletions, can be used as genetic markers in natural populations, especially in phylogenetic studies.[6][7] It has been shown that genomic regions with multiple indels can also be used for species-identification procedures.[8][9][10]
An indel change of a single base pair in the coding part of an mRNA results in a frameshift during mRNA translation that could lead to an inappropriate (premature) stop codon in a different frame. Indels that are not multiples of 3 are particularly uncommon in coding regions but relatively common in non-coding regions.[11][12] There are approximately 192-280 frameshifting indels in each person.[13] Indels are likely to represent between 16% and 25% of all sequence polymorphisms in humans.[14] In most known genomes, including humans, indel frequency tends to be markedly lower than that of single nucleotide polymorphisms (SNP), except near highly repetitive regions, including homopolymers and microsatellites.[15]
The term "indel" has been co-opted in recent years by genome scientists for use in the sense described above. This is a change from its original use and meaning, which arose from systematics. In systematics, researchers could find differences between sequences, such as from two different species. But it was impossible to infer if one species lost the sequence or the other species gained it. For example, species A has a run of 4 G nucleotides at a locus and species B has 5 G's at the same locus. If the mode of selection is unknown, one can not tell if species A lost one G (a "deletion" event") or species B gained one G (an "insertion" event). When one cannot infer the phylogenetic direction of the sequence change, the sequence change event is referred to as an "indel".[citation needed]
Using passenger-immunoglobulin mouse models, a study found that the most prevalent indel events are the activation-induced cytidine deaminase (AID)-dependent ±1-base pair (bp) indels, which can lead to deleterious outcomes, whereas longer in-frame indels were rare outcomes.[16]
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- ^ Hill KA, Wang J, Farwell KD, Sommer SS (January 2003). "Spontaneous tandem-base mutations (TBM) show dramatic tissue, age, pattern and spectrum specificity". Mutation Research. 534 (1–2): 173–186. doi:10.1016/S1383-5718(02)00277-2. PMID 12504766.
- ^ Buettner VL, Hill KA, Halangoda A, Sommer SS (1999). "Tandem-base mutations occur in mouse liver and adipose tissue preferentially as G:C to T:A transversions and accumulate with age". Environmental and Molecular Mutagenesis. 33 (4): 320–324. doi:10.1002/(SICI)1098-2280(1999)33:4<320::AID-EM9>3.0.CO;2-S. PMID 10398380. S2CID 37019230.
- ^ Väli U, Brandström M, Johansson M, Ellegren H (January 2008). "Insertion-deletion polymorphisms (indels) as genetic markers in natural populations". BMC Genetics. 9: 8. doi:10.1186/1471-2156-9-8. PMC 2266919. PMID 18211670.
- ^ Erixon P, Oxelman B (January 2008). Volff JN (ed.). "Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene". PLOS ONE. 3 (1): e1386. Bibcode:2008PLoSO...3.1386E. doi:10.1371/journal.pone.0001386. PMC 2148103. PMID 18167545.
- ^ Pereira F, Carneiro J, Matthiesen R, van Asch B, Pinto N, Gusmão L, Amorim A (December 2010). "Identification of species by multiplex analysis of variable-length sequences". Nucleic Acids Research. 38 (22): e203. doi:10.1093/nar/gkq865. PMC 3001097. PMID 20923781.
- ^ Nakamura H, Muro T, Imamura S, Yuasa I (March 2009). "Forensic species identification based on size variation of mitochondrial DNA hypervariable regions". International Journal of Legal Medicine. 123 (2): 177–184. doi:10.1007/s00414-008-0306-7. PMID 19052767. S2CID 10531572.
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- ^ Bai H, Cao Y, Quan J, Dong L, Li Z, Zhu Y, et al. (2013). "Identifying the genome-wide sequence variations and developing new molecular markers for genetics research by re-sequencing a Landrace cultivar of foxtail millet". PLOS ONE. 8 (9): e73514. Bibcode:2013PLoSO...873514B. doi:10.1371/journal.pone.0073514. PMC 3769310. PMID 24039970.
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- ^ Mills RE, Luttig CT, Larkins CE, Beauchamp A, Tsui C, Pittard WS, Devine SE (September 2006). "An initial map of insertion and deletion (INDEL) variation in the human genome". Genome Research. 16 (9): 1182–1190. doi:10.1101/gr.4565806. PMC 1557762. PMID 16902084.
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- ^ Hao, Qian; Zhan, Chuanzong; Lian, Chaoyang; Luo, Simin; Cao, Wenyi; Wang, Binbin; Xie, Xia; Ye, Xiaofei; Gui, Tuantuan; Voena, Claudia; Pighi, Chiara; Wang, Yanyan; Tian, Ying; Wang, Xin; Dai, Pengfei (2023-03-31). "DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification". Science Immunology. 8 (81): eade1167. doi:10.1126/sciimmunol.ade1167. ISSN 2470-9468. PMC 10351598. PMID 36961908.