High-density oligonucleotide array with sub-kilobase resolution reveals breakpoint information of submicroscopic deletions in nevoid basal cell carcinoma syndrome
Autor: | Yoichi Kohno, Hideki Uchikawa, Masao Yamada, Shumpei Ishikawa, Toshiyuki Miyashita, Keith W. Jones, Hiroyuki Aburatani, Fan Shen, Katsunori Fujii, Kimio Sasaki, Yoko Tanaka, Hiroshi Arai, Michael H. Shapero, Daisuke Komura, Jing Hung |
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Rok vydání: | 2007 |
Předmět: |
Male
Patched Receptors DNA Mutational Analysis Molecular Sequence Data Basal Cell Nevus Syndrome Receptors Cell Surface Nevoid basal-cell carcinoma syndrome Biology medicine.disease_cause Sequence Homology Nucleic Acid Genetics medicine Humans Child Gene Genetics (clinical) Oligonucleotide Array Sequence Analysis Sequence Deletion Southern blot Base Sequence Breakpoint DNA Neoplasm medicine.disease Molecular biology Human genetics Patched-1 Receptor PTCH1 Chromosomes Human Pair 9 Carcinogenesis |
Zdroj: | Human Genetics. 122:459-466 |
ISSN: | 1432-1203 0340-6717 |
Popis: | Small submicroscopic genomic deletions and duplications constitute up to 15% of all mutations underlying human monogenic diseases. In this study, we used newly designed high-resolution oligonucleotide microarrays with a median distance between the probes of 776 bp (average probe interval 2,271 bp) to detect gene deletions in nevoid basal cell carcinoma syndrome (NBCCS) patients. NBCCS, also called Gorlin syndrome, is characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the human patched-1 (PTCH1) gene. Two out of three deletions could not be detected by a conventional chromosomal analysis. A submicroscopic deletion as small as 165 kb was detected affecting only PTCH1, whereas the other two deletions were much larger (5 and 11 Mb). We demonstrated not only the exact number of genes involved in the deletion but also rapidly determined the junction sequences after pinpointing the breakpoint regions in all individuals analyzed. This report of an array-based determination of junction sequences of long deletions circumvented a labor-intensive analysis such as Southern blotting or FISH. Alu-mediated recombination in one case and non-homologous end joining in the other two were probably implicated in the generation of deletions. This method will contribute to the understanding of molecular pathogenesis of gene deletions as well as rapid genetic testing. |
Databáze: | OpenAIRE |
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