Copy number variation in regions flanked (or unflanked) by duplicons among patients with developmental delay and/or congenital malformations; detection of reciprocal and partial Williams-Beuren duplications
Open Access
- 14 December 2005
- journal article
- research article
- Published by Springer Nature in European Journal of Human Genetics
- Vol. 14 (2) , 180-189
- https://doi.org/10.1038/sj.ejhg.5201540
Abstract
Duplicons, that is, DNA sequences with minimum length 10 kb and a high sequence similarity, are known to cause unequal homologous recombination, leading to deletions and the reciprocal duplications. In this study, we designed a Multiplex Amplifiable Probe Hybridisation (MAPH) assay containing 63 exon-specific single-copy sequences from within a selection of the 169 regions flanked by duplicons that were identified, at a first pass, in 2001. Subsequently, we determined the frequency of chromosomal rearrangements among patients with developmental delay (DD) and/or congenital malformations (CM). In addition, we tried to identify new regions involved in DD/CM using the same assay. In 105 patients, six imbalances (5.8%) were detected and verified. Three of these were located in microdeletion-related regions, two alterations were polymorphic duplications and the effect of the last alteration is currently unknown. The same study population was tested for rearrangements in regions with no known duplicons nearby, using a set of probes derived from 58 function-selected genes. The latter screening revealed two alterations. As expected, the alteration frequency per unit of DNA is much higher in regions flanked by duplicons (fraction of the genome tested: 5.2%) compared to regions without known duplicons nearby (fraction of the genome tested: 24.5–90.2%). We were able to detect three novel rearrangements, including the previously undescribed reciprocal duplication of the Williams Beuren critical region, a subduplicon alteration within this region and a duplication on chromosome band 16p13.11. Our results support the hypothesis that regions flanked by duplicons are enriched for copy number variations.Keywords
This publication has 30 references indexed in Scilit:
- Insights from genomic microarrays into structural chromosome rearrangementsAmerican Journal of Medical Genetics Part A, 2004
- Detection of large-scale variation in the human genomeNature Genetics, 2004
- Uncommon Deletions of the Smith-Magenis Syndrome Region Can Be Recurrent When Alternate Low-Copy Repeats Act as Homologous Recombination SubstratesAmerican Journal of Human Genetics, 2004
- Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic featuresJournal of Medical Genetics, 2004
- Mutational Mechanisms of Williams-Beuren Syndrome DeletionsAmerican Journal of Human Genetics, 2003
- Human Nudel and NudE as Regulators of Cytoplasmic Dynein in Poleward Protein Transport along the Mitotic SpindleMolecular and Cellular Biology, 2003
- A Physical Map, Including a BAC/PAC Clone Contig, of the Williams-Beuren Syndrome–Deletion Region at 7q11.23American Journal of Human Genetics, 2000
- A Chromosomal Duplication Map of Malformations: Regions of Suspected Haplo- and Triplolethality—and Tolerance of Segmental Aneuploidy—in HumansAmerican Journal of Human Genetics, 1999
- Two autosomal dominant neuropathies result from reciprocal DNA duplication/deletion of a region on chromosome 17Human Molecular Genetics, 1994
- Partial deletion of long arm of chromosome 11[del(11)(q23)]: Jacobsen syndrome. Two new cases and review of the clinical findings.Journal of Medical Genetics, 1977