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.