Detection and precise mapping of germline rearrangements inBRCA1, BRCA2, MSH2, andMLH1using zoom-in array comparative genomic hybridization (aCGH)
| Autor: | Lina Tellhed, Therese Törngren, Åke Borg, Johan Staaf, Ulla Johansson, Eva Rambech, Gunilla Sellberg, Mef Nilbert, Camilla Persson |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Genes BRCA2 Genes BRCA1 Genetic Counseling Biology Germline Germline mutation CDKN2A Genetics Humans Multiplex Genetic Testing Multiplex ligation-dependent probe amplification Germ-Line Mutation Genetics (clinical) Adaptor Proteins Signal Transducing Oligonucleotide Array Sequence Analysis Sequence Deletion Gene Rearrangement Breakpoint Chromosome Mapping Nuclear Proteins Nucleic Acid Hybridization Genomics MutS Homolog 2 Protein MSH2 Female MutL Protein Homolog 1 Comparative genomic hybridization |
| Zdroj: | Human Mutation. 29:555-564 |
| ISSN: | 1059-7794 |
| DOI: | 10.1002/humu.20678 |
| Popis: | Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged from several 100 kb, including large flanking regions, to |
| Databáze: | OpenAIRE |
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