Project description:Comparative genomic hybridization microarrays (array CGH or molecular karyotyping) for the detection of congenital chromosomal aberrations is the application of microarray technology that is coming fastest into routine clinical application. When using a two-channel microarray of genomic DNA probes for array CGH, the basic setup consists in hybridizing a patient sample against a normal reference sample and detecting copy number variations through the deviation of fluorescent signal intensity between patient and normal reference. Two major disadvantages of this setup are (1) the use of half of the resources to measure a (little informative) reference sample and (2) the possibility that deviating signals are caused by benign copy number variation in the ânormalâ reference instead of a patient aberration. We therefore propose a new experimental loop design that compares three patients in three hybridizations (Patient 1 vs. Patient 3, Patient 3 vs. Patient 2, and Patient 2 vs. Patient 1). We develop and compare two statistical methods (linear models of log ratios and mixed models of absolute measurements). In an analysis of data from 27 patients seen at our genetics center, this new setup together with the linear model analysis significantly overcomes the limitations of the classical setup. Furthermore, we observed that the linear models of the log-ratios had a higher signal-to-noise ratio than the mixed models of the absolute intensities. These improvements are important to guarantee a maximal efficiency of array CGH in a clinical setting and will therefore contribute to its quick adoption as a routine diagnostic tool. The method is implemented as a web application and is available at www.esat.kuleuven.be/loop. Keywords: comparative genomic hybridization The data set consists out of nine loop designs or 27 patients with mental retardation (MR) and multiple congenital anomalies (MCA). The patients were seen at our genetics center (Center for Human Genetics, U.Z.Leuven).

Project description:Data underlying Sander et al., Oncogene 2005, June 20, Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Includes both array CGH and expression data. Abstract: Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing approximately 14,000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3-3H4, and recurrent amplifications at chromosome 3F2.1-3G3 and chromosome 15E1/E2-15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Using regression correlation

Project description:Data underlying Sander et al., Oncogene 2005, June 20, Comparative genomic hybridization on mouse cDNA microarrays and its application to a murine lymphoma model. Includes both array CGH and expression data. Abstract: Microarray-based formats offer a high-resolution alternative to conventional, chromosome-based comparative genomic hybridization (CGH) methods for assessing DNA copy number alteration (CNA) genome-wide in human cancer. For murine tumors, array CGH should provide even greater advantage, since murine chromosomes are more difficult to individually discern. We report here the adaptation and evaluation of a cDNA microarray-based CGH method for the routine characterization of CNAs in murine tumors, using mouse cDNA microarrays representing approximately 14,000 different genes, thereby providing an average mapping resolution of 109 kb. As a first application, we have characterized CNAs in a set of 10 primary and recurrent lymphomas derived from a Myc-induced murine lymphoma model. In primary lymphomas and more commonly in Myc-independent relapses, we identified a recurrent genomic DNA loss at chromosome 3G3-3H4, and recurrent amplifications at chromosome 3F2.1-3G3 and chromosome 15E1/E2-15F3, the boundaries of which we defined with high resolution. Further, by profiling gene expression using the same microarray platform, we identified within CNAs the relevant subset of candidate cancer genes displaying comparably altered expression, including Mcl1 (myeloid cell leukemia sequence 1), a highly expressed antiapoptotic gene residing within the chr 3 amplicon peak. CGH on mouse cDNA microarrays therefore represents a reliable method for the high-resolution characterization of CNAs in murine tumors, and a powerful approach for elucidating the molecular events in tumor development and progression in murine models. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design, arrayCGH, expression profiling

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An experimental loop design improves the detection of congenital chromosomal aberrations by array CGH

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