Niskoponavljajuća kopija

Niskoponavljajuća kopija (LCR), također poznata kao segmentne duplikacije (SD), ili duplikoni, su sekvence DNK prisutne na više lokacija unutar genoma koje dijele visok nivo identiteta sekvence.

Ponavljanja

Ponavljanja, ili duplikacije, obično su dugačke 10–300 kb i čine više od 95% identiteta sekvence. Iako rijetka kod većine sisara, LCR-ovi čine veliki dio ljudskog genoma zbog značajne ekspanzije tokom evolucije primata.^[1] Kod ljudi, hromosomi Y i 22 imaju najveći udio standardnih devijacija: 50,4% odnosno 11,9%^[2] SRGAP2 je SD.

Neusklađenost LCR-ova tokom nealelne homologne rekombinacije (NAHR)^[3] je važan mehanizam koji leži u osnovi hromosomskih mikrodelecijskih poremećaja, kao i njihovih recipročnih duplikacijskih partnera.^[4] Mnogi LCR-ovi su koncentrirani u "vrućim tačkama", kao što je regija 17p11-12, od kojih se 27% sastoji od LCR sekvence. NAHR i nehomologno spajanje krajeva (NHEJ) unutar ove regije odgovorni su za širok spektar poremećaja, uključujući Charcot-Marie-Toothov sindrom tip 1A,^[5] nasljedna neuropatija sa sklonošću ka paralizama uzrokovanim pritiskom,^[5] Smith-Magenisov,^[6] i Potocki–Lupskijev sindrom.^[3]

Detekcija

Postoje dva široko prihvaćena metoda za detekciju SD-a:^[7]

1. Poređenje sklopa cijelog genoma (WGAC), u kojem se identificiraju regije homologije unutar sklopa.
2. Detekcija sekvenci cijelog genoma pomoću sačmarice (WSSD), u kojoj se duplikacija regija zaključuje povećanom pokrivenost čitanja na mjestu segmentne duplikacije.

Također pogledajte

Reference

↑ Johnson, M.E. (2008). Primate Gene and Genome Evolution Driven by Segmental Duplication of Chromosome 16 (PDF) (Ph.D.). Case Western Reserve University.
↑ Bailey, Jeffrey A.; Eichler, EE (2006). "Primate segmental duplications: crucibles of evolution, diversity and disease". Nature Reviews Genetics. 7 (7): 552–64. doi:10.1038/nrg1895. PMID 16770338. S2CID 3203768.
1 2 Zhang, F; Potocki, L; Sampson, JB; Liu, P; Sanchez-Valle, A; Robbins-Furman, P; Navarro, AD; Wheeler, PG; Spence, JE; Brasington, CK; Withers, MA; Lupski, JR (12. 3. 2010). "Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS". American Journal of Human Genetics. 86 (3): 462–70. doi:10.1016/j.ajhg.2010.02.001. PMC 2833368. PMID 20188345.
↑ Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM; Zackai, EH; Budarf, ML; Emanuel, BS (1. 3. 2000). "Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis". Human Molecular Genetics. 9 (4): 489–501. doi:10.1093/hmg/9.4.489. PMID 10699172.
1 2 Inoue, K; Dewar, K; Katsanis, N; Reiter, LT; Lander, ES; Devon, KL; Wyman, DW; Lupski, JR; Birren, B (juni 2001). "The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes". Genome Research. 11 (6): 1018–33. doi:10.1101/gr.180401. PMC 311111. PMID 11381029.
↑ Shaw, CJ; Withers, MA; Lupski, JR (juli 2004). "Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when alternate low-copy repeats act as homologous recombination substrates". American Journal of Human Genetics. 75 (1): 75–81. doi:10.1086/422016. PMC 1182010. PMID 15148657.
↑ "Genome-wide detection of segmental duplications".

Šablon:Ponovljena sekvenca

[1] Johnson, M.E. (2008). Primate Gene and Genome Evolution Driven by Segmental Duplication of Chromosome 16 (PDF) (Ph.D.). Case Western Reserve University.

[2] Bailey, Jeffrey A.; Eichler, EE (2006). "Primate segmental duplications: crucibles of evolution, diversity and disease". Nature Reviews Genetics. 7 (7): 552–64. doi:10.1038/nrg1895. PMID 16770338. S2CID 3203768.

[pmid20188345-3] 1 2 Zhang, F; Potocki, L; Sampson, JB; Liu, P; Sanchez-Valle, A; Robbins-Furman, P; Navarro, AD; Wheeler, PG; Spence, JE; Brasington, CK; Withers, MA; Lupski, JR (12. 3. 2010). "Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS". American Journal of Human Genetics. 86 (3): 462–70. doi:10.1016/j.ajhg.2010.02.001. PMC 2833368. PMID 20188345.

[4] Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM; Zackai, EH; Budarf, ML; Emanuel, BS (1. 3. 2000). "Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis". Human Molecular Genetics. 9 (4): 489–501. doi:10.1093/hmg/9.4.489. PMID 10699172.

[pmid11381029-5] 1 2 Inoue, K; Dewar, K; Katsanis, N; Reiter, LT; Lander, ES; Devon, KL; Wyman, DW; Lupski, JR; Birren, B (juni 2001). "The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes". Genome Research. 11 (6): 1018–33. doi:10.1101/gr.180401. PMC 311111. PMID 11381029.

[pmid15148657-6] Shaw, CJ; Withers, MA; Lupski, JR (juli 2004). "Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when alternate low-copy repeats act as homologous recombination substrates". American Journal of Human Genetics. 75 (1): 75–81. doi:10.1086/422016. PMC 1182010. PMID 15148657.

[7] "Genome-wide detection of segmental duplications".

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