Biology:Low copy repeats
Low copy repeats (LCRs), also known as segmental duplications (SDs), are DNA sequences present in multiple locations within a genome that share high levels of sequence identity.
Repeats
The repeats, or duplications, are typically 10–300 kb in length, and bear greater than 95% sequence identity. Though rare in most mammals, LCRs comprise a large portion of the human genome owing to a significant expansion during primate evolution.[1] In humans, chromosomes Y and 22 have the greatest proportion of SDs: 50.4% and 11.9% respectively.[2]
Misalignment of LCRs during non-allelic homologous recombination (NAHR)[3] is an important mechanism underlying the chromosomal microdeletion disorders as well as their reciprocal duplication partners.[4] Many LCRs are concentrated in "hotspots", such as the 17p11-12 region, 27% of which is composed of LCR sequence. NAHR and non-homologous end joining (NHEJ) within this region are responsible for a wide range of disorders, including Charcot–Marie–Tooth syndrome type 1A,[5] hereditary neuropathy with liability to pressure palsies,[5] Smith–Magenis syndrome,[6] and Potocki–Lupski syndrome.[3]
Detection
The two widely accepted methods for SD detection[7] are:
- 1. Whole-genome assembly comparison (WGAC), in which regions of homology within the assembly are identified.
- 2. Whole-genome shotgun sequence detection (WSSD), in which the duplication of regions is inferred by increased read coverage at the site of segmental duplication.
See also
- Pseudogenes
- Molecular evolution
- Comparative genomics
- Inparanoid
- Tandem exon duplication
- 1q21.1 copy number variations
- Segmental duplication on the human Y chromosome
References
- ↑ 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.
- ↑ 3.0 3.1 Zhang, F; Potocki, L; Sampson, JB; Liu, P; Sanchez-Valle, A; Robbins-Furman, P; Navarro, AD; Wheeler, PG et al. (12 March 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. PMID 20188345.
- ↑ Shaikh, TH; Kurahashi, H; Saitta, SC; O'Hare, AM; Hu, P; Roe, BA; Driscoll, DA; McDonald-McGinn, DM et al. (1 March 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.
- ↑ 5.0 5.1 Inoue, K; Dewar, K; Katsanis, N; Reiter, LT; Lander, ES; Devon, KL; Wyman, DW; Lupski, JR et al. (June 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. PMID 11381029.
- ↑ Shaw, CJ; Withers, MA; Lupski, JR (July 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. PMID 15148657.
- ↑ "Genome-wide detection of segmental duplications". http://genomebiology.com/2003/4/4/R25.
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