Molecular-evolutionary mechanisms for genomic disorders

Molecular studies of unstable regions in the human genome have identified region-specific low-copy repeats (LCRs). Unlike highly repetitive sequences (e.g. Alus and LINEs), LCRs are usually of 10-400 kb in size and exhibit greater than or equal to 95-97% similarity. According to computer analyses of available sequencing data, LCRs may constitute >5% of the human genome. Through the process of non-allelic homologous recombination using paralogous genomic segments as substrates, LCRs have been shown to facilitate meiotic DNA rearrangements associated with disease traits, referred to as genomic disorders. In addition, this LCR-based complex genome architecture appears to play a major role in both primate karyotype evolution and human tumorigenesis.