Comprehensive Detection of Genomic Duplications and Deletions in the DMD Gene, by Use of Multiplex Amplifiable Probe Hybridization
| Autor: | Dieuwke Engelsma, Gert-Jan B. van Ommen, Marjolein Kriek, Margot E. Kalf, Martijn H. Breuning, Johan T. den Dunnen, Bert Bakker, Ellen Vollebregt, Michel P. Villerius, Stefan J. White, Qiang Liu |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Duchenne muscular dystrophy Biology medicine.disease_cause Polymerase Chain Reaction law.invention Dystrophin Exon law Gene Duplication Gene duplication medicine Genetics Humans Genetics(clinical) Muscular dystrophy Gene Genetics (clinical) Polymerase chain reaction Sequence Deletion Mutation Articles Exons medicine.disease Muscular Dystrophy Duchenne genomic DNA Female |
| Zdroj: | ResearcherID |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/341942 |
| Popis: | Duplications and deletions are known to cause a number of genetic disorders, yet technical difficulties and financial considerations mean that screening for these mutations, especially duplications, is often not performed. We have adapted multiplex amplifiable probe hybridization (MAPH) for the screening of the DMD gene, mutations in which cause Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy. MAPH involves the quantitative recovery of specifically designed probes following hybridization to immobilized genomic DNA. We have engineered probes for each of the 79 exons of the DMD gene, and we analyzed them by using a 96-capillary sequencer. We screened 24 control individuals, 102 patients, and 23 potential carriers and detected a large number of novel rearrangements, especially small, one- and two-exon duplications. A duplication of exon 2 alone was the most frequently occurring mutation identified. Our analysis indicates that duplications occur in 6% of patients with DMD. The MAPH technique as modified here is simple, quick, and accurate; furthermore, it is based on existing technology (i.e., hybridization, PCR, and electrophoresis) and should not require new equipment. Together, these features should allow easy implementation in routine diagnostic laboratories. Furthermore, the methodology should be applicable to any genetic disease, it should be easily expandable to cover >200 probes, and its characteristics should facilitate high-throughput screening. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|