low copy repeats
{{more citations needed|date=March 2009}}
Low copy repeats (LCRs), also known as segmental duplications (SDs), or duplicons, 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.{{cite thesis|url=http://etd.ohiolink.edu/send-pdf.cgi/Johnson%20Matthew%20Eric.pdf?case1190140658|title=Primate Gene and Genome Evolution Driven by Segmental Duplication of Chromosome 16|last=Johnson|first=M.E.|type=Ph.D.|date=2008|publisher=Case Western Reserve University}} In humans, chromosomes Y and 22 have the greatest proportion of SDs: 50.4% and 11.9% respectively.{{Cite journal
| doi = 10.1038/nrg1895
| title = Primate segmental duplications: crucibles of evolution, diversity and disease
| year = 2006
| author = Bailey, Jeffrey A.
| journal = Nature Reviews Genetics
| volume = 7
| pages = 552–64
| pmid = 16770338
| last2 = Eichler
| first2 = EE
| issue = 7
| s2cid = 3203768
}} SRGAP2 is an SD.
Misalignment of LCRs during non-allelic homologous recombination (NAHR){{cite journal|last1=Zhang|first1=F|last2=Potocki|first2=L|last3=Sampson|first3=JB|last4=Liu|first4=P|last5=Sanchez-Valle|first5=A|last6=Robbins-Furman|first6=P|last7=Navarro|first7=AD|last8=Wheeler|first8=PG|last9=Spence|first9=JE|last10=Brasington|first10=CK|last11=Withers|first11=MA|last12=Lupski|first12=JR|title=Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS.|journal=American Journal of Human Genetics|date=12 March 2010|volume=86|issue=3|pages=462–70|doi=10.1016/j.ajhg.2010.02.001|pmid=20188345|pmc=2833368}} is an important mechanism underlying the chromosomal microdeletion disorders as well as their reciprocal duplication partners.{{cite journal|last1=Shaikh|first1=TH|last2=Kurahashi|first2=H|last3=Saitta|first3=SC|last4=O'Hare|first4=AM|last5=Hu|first5=P|last6=Roe|first6=BA|last7=Driscoll|first7=DA|last8=McDonald-McGinn|first8=DM|last9=Zackai|first9=EH|author9-link=Elaine Zackai|last10=Budarf|first10=ML|last11=Emanuel|first11=BS|title=Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis.|journal=Human Molecular Genetics|date=1 March 2000|volume=9|issue=4|pages=489–501|doi=10.1093/hmg/9.4.489|pmid=10699172|doi-access=free}} 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,{{cite journal|last1=Inoue|first1=K|last2=Dewar|first2=K|last3=Katsanis|first3=N|last4=Reiter|first4=LT|last5=Lander|first5=ES|last6=Devon|first6=KL|last7=Wyman|first7=DW|last8=Lupski|first8=JR|last9=Birren|first9=B|title=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.|journal=Genome Research|date=June 2001|volume=11|issue=6|pages=1018–33|doi=10.1101/gr.180401|pmid=11381029|pmc=311111}} hereditary neuropathy with liability to pressure palsies, Smith–Magenis syndrome,{{cite journal|last1=Shaw|first1=CJ|last2=Withers|first2=MA|last3=Lupski|first3=JR|title=Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when alternate low-copy repeats act as homologous recombination substrates.|journal=American Journal of Human Genetics|date=July 2004|volume=75|issue=1|pages=75–81|doi=10.1086/422016|pmid=15148657|pmc=1182010}} and Potocki–Lupski syndrome.
Detection
The two widely accepted methods for SD detection{{Cite web|url=http://genomebiology.com/2003/4/4/R25|title=Genome-wide detection of segmental duplications}} 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.