BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH) - PubMed (original) (raw)

Review

. 2006 Jan 26;34(2):445-50.

doi: 10.1093/nar/gkj456. Print 2006.

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Review

BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH)

Bauke Ylstra et al. Nucleic Acids Res. 2006.

Abstract

The array CGH technique (Array Comparative Genome Hybridization) has been developed to detect chromosomal copy number changes on a genome-wide and/or high-resolution scale. It is used in human genetics and oncology, with great promise for clinical application. Until recently primarily PCR amplified bacterial artificial chromosomes (BACs) or cDNAs have been spotted as elements on the array. The large-scale DNA isolations or PCR amplifications of the large-insert clones necessary for manufacturing the arrays are elaborate and time-consuming. Lack of a high-resolution highly sensitive (commercial) alternative has undoubtedly hindered the implementation of array CGH in research and diagnostics. Recently, synthetic oligonucleotides as arrayed elements have been introduced as an alternative substrate for array CGH, both by academic institutions as well as by commercial providers. Oligonucleotide libraries or ready-made arrays can be bought off-the-shelf saving considerable time and efforts. For RNA expression profiling, we have seen a gradual transition from in-house printed cDNA-based expression arrays to oligonucleotide arrays and we expect a similar transition for array CGH. This review compares the different platforms and will attempt to shine a light on the 'BAC to the future' of the array CGH technique.

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Figures

Figure 1

Figure 1

Relation between theoretical and measured chromosomal copy number changes for several different platforms. Number of chromosomes on the horizontal axis and the dye normalized experimental ratios on the vertical axis. Agilent custom oaCGH (25), speckled gray line with diamonds, slope 0.53; BAC arrays (3), thin line with dots, slope 0.37; in-house printed oaCGH (14), short dashes line with plusses, slope 0.28; Agilent oaCGH on expression arrays (25), dark gray line with triangles slope 0.21. A single chromosomal copy gain in a diploid background theoretically shifts the ratio from 1 to 1.5 (two chromosomes/two chromosomes versus three chromosomes/two chromosomes). To detect a single copy gain in a diploid background, the total variance should therefore be smaller than 0.25 so that there is no overlap between normal and gain. The copy number values and slope for the Agilent CGH platform (25) is nearly identical to the theoretical values and slope. However, the variance for one or even three array elements combined is too high to unequivocally call a gain (Table 1). The relation between the theoretical and measured chromosomal copy number change for a given BAC array is slightly compressed, but the variance is maximally 0.18 (Table 1). This makes it possible to make a call on a single arrayed BAC element. For the in-house printed oaCGH platform the relation between theoretical and measured chromosomal copy number is also not ideal; however, three oligonucleotides are still sufficient to call a single copy number change, since the elements have a limited variance (Table 1). The ROMA or NimbleGen platforms could not be included, since raw log2 ratios were not available. The Affymetrix (22) platform was not included since it is a single channel array and this figure presents normalized ratios.

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