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 > or = 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.
Stankiewicz
Pawel
P
Department of Molecular and Human Genetics, Baylor College of Medicine, Room 604B, One Baylor Plaza, and Texas Children Hospital, Houston, Texas 77030-3498, USA.
Lupski
James R
JR
D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics; D019143:Evolution, Molecular; D005785:Gene Conversion; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D018980:Williams Syndrome / Q000235:genetics
D009185:Myelin Proteins; C073687:PMP22 protein, human