OBJECTIVE: High resolution detection of genomic copy number abnormalities in a single cell is relevant to preimplantation genetic diagnosis and potentially to noninvasive prenatal diagnosis. Our objective is to develop a reliable array comparative genomic hybridization (CGH) platform to detect genomic imbalances as small as ~1Mb ina single cell. METHODS: We empirically optimized the conditions for oligonucleotide-based array CGH using single cells from multiple lymphoblastoid cell lines with known copy number abnormalities. To improve resolution, we designed custom arrays with high density probes covering clinically relevant genomic regions. RESULTS: The detection of megabase-sized copy number variations (CNVs) in a single cell was influenced by the number of probes clustered in the interrogated region. Using our custom array, we reproducibly detected multiple chromosome abnormalities including trisomy 21, a 1.2Mb Williams syndrome deletion, and a 1.3Mb CMT1A duplication. Replicate analyses yielded consistent results. CONCLUSION: Aneuploidy and genomic imbalances with CNVs as small as 1.2Mb in a single cell are detectable by array CGH using arrays with high-density coverage in the targeted regions. This approach has the potential to be applied for preimplantation genetic diagnosis to detect aneuploidy and common microdeletion/duplication syndromes and for noninvasive prenatal diagnosis if single fetal cells can be isolated.
OBJECTIVE: High resolution detection of genomic copy number abnormalities in a single cell is relevant to preimplantation genetic diagnosis and potentially to noninvasive prenatal diagnosis. Our objective is to develop a reliable array comparative genomic hybridization (CGH) platform to detect genomic imbalances as small as ~1Mb ina single cell. METHODS: We empirically optimized the conditions for oligonucleotide-based array CGH using single cells from multiple lymphoblastoid cell lines with known copy number abnormalities. To improve resolution, we designed custom arrays with high density probes covering clinically relevant genomic regions. RESULTS: The detection of megabase-sized copy number variations (CNVs) in a single cell was influenced by the number of probes clustered in the interrogated region. Using our custom array, we reproducibly detected multiple chromosome abnormalities including trisomy 21, a 1.2Mb Williams syndrome deletion, and a 1.3Mb CMT1A duplication. Replicate analyses yielded consistent results. CONCLUSION:Aneuploidy and genomic imbalances with CNVs as small as 1.2Mb in a single cell are detectable by array CGH using arrays with high-density coverage in the targeted regions. This approach has the potential to be applied for preimplantation genetic diagnosis to detect aneuploidy and common microdeletion/duplication syndromes and for noninvasive prenatal diagnosis if single fetal cells can be isolated.
Authors: Birte Möhlendick; Christoph Bartenhagen; Bianca Behrens; Ellen Honisch; Katharina Raba; Wolfram T Knoefel; Nikolas H Stoecklein Journal: PLoS One Date: 2013-06-25 Impact factor: 3.240
Authors: Laia Ramos; Javier del Rey; Gemma Daina; Manel García-Aragonés; Lluís Armengol; Alba Fernandez-Encinas; Mònica Parriego; Montserrat Boada; Olga Martinez-Passarell; Maria Rosa Martorell; Oriol Casagran; Jordi Benet; Joaquima Navarro Journal: PLoS One Date: 2014-11-21 Impact factor: 3.240
Authors: Thierry Voet; Parveen Kumar; Peter Van Loo; Susanna L Cooke; John Marshall; Meng-Lay Lin; Masoud Zamani Esteki; Niels Van der Aa; Ligia Mateiu; David J McBride; Graham R Bignell; Stuart McLaren; Jon Teague; Adam Butler; Keiran Raine; Lucy A Stebbings; Michael A Quail; Thomas D'Hooghe; Yves Moreau; P Andrew Futreal; Michael R Stratton; Joris R Vermeesch; Peter J Campbell Journal: Nucleic Acids Res Date: 2013-04-29 Impact factor: 16.971