Low copy repeats explained

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, Smith–Magenis syndrome,^[6] and Potocki–Lupski syndrome.

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

Notes and References

1. Primate Gene and Genome Evolution Driven by Segmental Duplication of Chromosome 16. Johnson. M.E.. Ph.D.. 2008. Case Western Reserve University.
2. 10.1038/nrg1895 . Primate segmental duplications: crucibles of evolution, diversity and disease . 2006 . Bailey, Jeffrey A. . Nature Reviews Genetics . 7 . 552–64 . 16770338 . Eichler . EE . 7. 3203768 .
3. 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. Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS.. American Journal of Human Genetics. 12 March 2010. 86. 3. 462–70. 10.1016/j.ajhg.2010.02.001. 20188345. 2833368.
4. Shaikh. TH. Kurahashi. H. Saitta. SC. O'Hare. AM. Hu. P. Roe. BA. Driscoll. DA. McDonald-McGinn. DM. Zackai. EH. Elaine Zackai. Budarf. ML. Emanuel. BS. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.. Human Molecular Genetics. 1 March 2000. 9. 4. 489–501. 10.1093/hmg/9.4.489. 10699172. free.
5. Inoue. K. Dewar. K. Katsanis. N. Reiter. LT. Lander. ES. Devon. KL. Wyman. DW. Lupski. JR. Birren. B. 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. June 2001. 11. 6. 1018–33. 10.1101/gr.180401. 11381029. 311111.
6. Shaw. CJ. Withers. MA. Lupski. JR. 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. July 2004. 75. 1. 75–81. 10.1086/422016. 15148657. 1182010.
7. Web site: Genome-wide detection of segmental duplications.