scholarly journals Bacterial Artificial Chromosome Array-based Comparative Genomic Hybridization

2020 ◽  
Author(s):  
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3382-3382
Author(s):  
Frank G. Rucker ◽  
Carsten Schwanen ◽  
Daniel Lipka ◽  
Swen Wessendorf ◽  
Stefan Frohling ◽  
...  

Abstract Approximately 10 to 15 % of acute myeloid leukemia (AML) cases exhibit complex karyotypes, i.e., three or more chromosome abnormalities without presence of a specific fusion transcript. Using chromosome banding analysis, the majority of such cases cannot be completely described due to the low resolution of this method. Comparative genomic hybridization to microarrays (matrix-CGH) is a novel technique that allows genome-wide screening for genomic imbalances at high resolution and thus may facilitate the identification of novel regions harboring potential disease-related genes. We constructed a microarray consisting of 2799 different human genomic DNA fragments cloned in bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC) vectors. A set of 1502 of these clones covers the whole human genome with a physical distance of approximately 2 Mb. The remaining 1297 clones either contiguously span genomic regions known to be frequently involved in hematologic malignancies (e.g., 1p, 2p, 3q, 7q, 9p, 11q, 12q, 13q, 17p, 18q) (n=610) or contain oncogenes or tumor suppressor genes (n=687). In this study 45 AML cases with complex karyotypes were analyzed. Matrix-CGH detected genomic aberrations in all cases and genomic losses were found more frequently than gains. The most frequent aberration was deletion 5q in 38 of 45 cases. Three consensus regions were delineated mapping to chromosomal bands 5q11 (23 cases), 5q34 (22 cases), and 5q35 (21 cases). Further frequent deletions affected 17p (60%); two consensus regions were identified mapping to chromosomal bands 17p13 (60%), and 17p11-q11 (33%). Other chromosomal losses affected 7q (51%), 16p (31%), 16q, 18q (29% each), 15q (24%), 10p (22%), 14q, 4p (20% each), 11q, 20q (18% each), 3p, and 12p (15% each). The most frequent genomic gain was identified at 8q (40%). Further frequent gains were detected on 11q (38%), 21q (27%), 1p, 2q (24% each), 9p (22%), 6p, 19p (20% each), 3q (18%), 7p, 20p (15% each), 13q, and 20q (13% each). Genomic amplifications were identified on chromosomal band 8q24 including the MYC gene (2 cases), 9p24 (JAK2, 2 cases), 10p15 (PRKCO, 1 case), 11q23 (MLL, 2 cases), 11q23.3 (ETS1 and FLI1, 2 cases each), 12p13 (CCND2 and FGF6, 2 cases), 13q12 (CDX2, 3 cases), 20q11.1 (BCL2L, 1 case), 21p (1 case), 21q (2 cases), and 22q (1 case). These data demonstrate the potential of matrix-CGH with regard to spatial resolution and sensitive detection of genomic imbalances. Analysis of a large series of AML cases with complex karyotype may lead to the identification of novel critical regions and pathogenetically relevant genes.


2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Jeffrey C. Miecznikowski ◽  
Daniel P. Gaile ◽  
Song Liu ◽  
Lori Shepherd ◽  
Norma Nowak

The main focus in pin-tip (or print-tip) microarray analysis is determining which probes, genes, or oligonucleotides are differentially expressed. Specifically in array comparative genomic hybridization (aCGH) experiments, researchers search for chromosomal imbalances in the genome. To model this data, scientists apply statistical methods to the structure of the experiment and assume that the data consist of the signal plus random noise. In this paper we propose “SmoothArray”, a new method to preprocess comparative genomic hybridization (CGH) bacterial artificial chromosome (BAC) arrays and we show the effects on a cancer dataset. As part of our R software package “aCGHplus,” this freely available algorithm removes the variation due to the intensity effects, pin/print-tip, the spatial location on the microarray chip, and the relative location from the well plate. removal of this variation improves the downstream analysis and subsequent inferences made on the data. Further, we present measures to evaluate the quality of the dataset according to the arrayer pins, 384-well plates, plate rows, and plate columns. We compare our method against competing methods using several metrics to measure the biological signal. With this novel normalization algorithm and quality control measures, the user can improve their inferences on datasets and pinpoint problems that may arise in their BAC aCGH technology.


2004 ◽  
Vol 171 (4S) ◽  
pp. 150-151
Author(s):  
Thorsten Schlomm ◽  
Bastian Gunawan ◽  
Hans J. Schulten ◽  
Norbert Graf ◽  
Ivo Leuschner ◽  
...  

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