Structure and Evolution of the Smith-Magenis Syndrome Repeat Gene Clusters, SMS-REPs
Open Access
- 1 May 2002
- journal article
- Published by Cold Spring Harbor Laboratory in Genome Research
- Vol. 12 (5) , 729-738
- https://doi.org/10.1101/gr.82802
Abstract
An ∼4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is located between them. SMS-REPs are believed to mediate nonallelic homologous recombination, resulting in both SMS deletions and reciprocal duplications. To delineate the genomic structure and evolutionary origin of SMS-REPs, we constructed a bacterial artificial chromosome/P1 artifical chromosome contig spanning the entire SMS region, including the SMS-REPs, determined its genomic sequence, and used fluorescence in situ hybridization to study the evolution of SMS-REP in several primate species. Our analysis shows that both the proximal SMS-REP (∼256 kb) and the distal copy (∼176 kb) are located in the same orientation and derived from a progenitor copy, whereas the middle SMS-REP (∼241 kb) is inverted and appears to have been derived from the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were duplicated after the divergence of New World monkeys from pre-monkeys ∼40–65 million years ago. Our findings potentially explain why the vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and distal SMS-REPs and further support previous observations that higher-order genomic architecture involving LCRs arose recently during primate speciation and may predispose the human genome to both meiotic and mitotic rearrangements.Keywords
This publication has 46 references indexed in Scilit:
- Molecular Characterization and Gene Content of Breakpoint Boundaries in Patients with Neurofibromatosis Type 1 with 17q11.2 MicrodeletionsAmerican Journal of Human Genetics, 2001
- The Evolutionary Chromosome Translocation 4;19 inGorilla gorillais Associated with Microduplication of the Chromosome Fragment Syntenic to Sequences Surrounding the Human Proximal CMT1A-REPGenome Research, 2001
- Initial sequencing and analysis of the human genomeNature, 2001
- Fine-Scale Comparative Mapping of the Human 7q11.23 Region and the Orthologous Region on Mouse Chromosome 5G: The Low-Copy Repeats That Flank the Williams–Beuren Syndrome Deletion Arose at Breakpoint Sites of an Evolutionary Inversion(s)Genomics, 2000
- An Anchored Framework BAC Map of Mouse Chromosome 11 Assembled Using Multiplex Oligonucleotide HybridizationGenomics, 1998
- The Charcot–Marie–Tooth Binary Repeat Contains a Gene Transcribed from the Opposite Strand of a Partially Duplicated Region of theCOX10GeneGenomics, 1997
- Homologous recombination of a flanking repeat gene cluster is a mechanism for a common contiguous gene deletion syndromeNature Genetics, 1997
- The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPsHuman Molecular Genetics, 1997
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Primate origin of the CMT1A-REP repeat and analysis of a putative transposon-associated recombinational hotspotHuman Molecular Genetics, 1996