Low copy repeats in the genome: from neglected to respected

Abstract

DNA paralogs that have a length of at least 1 kilobase (kb) and are duplicated with a sequence identity of over 90% are classified as low copy repeats (LCRs) or segmental duplications (SDs). They constitute 6.6% of the genome and are clustering in specific genomic loci. Due to the high sequence homology between these duplicated regions, they can misalign during meiosis resulting in non-allelic homologous recombination (NAHR) and leading to structural variation such as deletions, duplications, inversions, and translocations. When such rearrangements result in a clinical phenotype, they are categorized as a genomic disorder. The presence of multiple copies of larger genomic segments offers opportunities for evolution. First, the creation of new genes in the human lineage will lead to human-specific traits and adaptation. Second, LCR variation between human populations can give rise to phenotypic variability. Hence, the rearrangement predisposition associated with LCRs should be interpreted in the context of the evolutionary advantages.

Structural Variation Evolution at the 15q11-q13 Disease-Associated Locus

“…Central to an understanding of structural variation is the interspersed segmental duplication (SD) architecture of human and ape genomes. Many structural variations are not random events but occur as a result of unequal crossovers between SDs, which act as catalysts for genomic instability with profound consequences in evolution and human disease [1,[4][5][6][7][8][9][10][11][12][13][14][15][16][17].…”