High resolution profiling of X chromosomal aberrations by array comparative genomic hybridisation

Veltman, Joris A.; Yntema, Helger G.; Lugtenberg, Dorien; Arts, Heleen H.; Briault, Sylvain; Huys, Erik; Osoegawa, Kazutoyo; Jong, Pieter J. de; Brunner, Han G.; Kessel, A.H.M. Geurts van; Bokhoven, Hans van; Schoenmakers, Eric

doi:10.1136/jmg.2004.018531

Cited by 51 publications

(34 citation statements)

References 33 publications

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“…8,9 Array CGH has been applied for high resolution analysis of constitutional abnormalities in specific chromosomal regions, 10 -12 including subtelomeric regions of all chromosomes, 13 specific targeted chromosome regions such as 15q11.2, 14 and entire chromosomes, such as chromosomes 22 and X. 15,16 DNA arrays consisting of 2,000 to 4,000 BAC clones representing the sequenced genome at approximately 1-Mb intervals have also been developed. 17,18 A study using a tiling path DNA microarray with complete coverage of the human genome with 32,433 overlapping BAC clones with the potential to identify disease genes has been reported.…”

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confidence: 99%

Development and validation of a CGH microarray for clinical cytogenetic diagnosis

Cheung

Shaw

et al. 2005

Genetics in Medicine

237

266

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Purpose: We developed a microarray for clinical diagnosis of chromosomal disorders using large insert genomic DNA clones as targets for comparative genomic hybridization (CGH). Methods: The array contains 362 FISH-verified clones that span genomic regions implicated in over 40 known human genomic disorders and representative subtelomeric clones for each of the 41 clinically relevant human chromosome telomeres. Three or four clones from almost all deletion or duplication genomic regions and three or more clones for each subtelomeric region were included. We tested chromosome microarray analysis (CMA) in a masked fashion by examining genomic DNA from 25 patients who were previously ascertained in a genetic clinic and studied by conventional cytogenetics. A novel software package implemented in the R statistical programming language was developed for normalization, visualization, and inference. Results: The CMA results were entirely consistent with previous cytogenetic and FISH findings. For clone by clone analysis, the sensitivity was estimated to be 96.7% and the specificity was 99.1%.Major advantages of this selected human genome array include the following: interrogation of clinically relevant genomic regions, the ability to test for a wide range of duplication and deletion syndromes in a single analysis, the ability to detect duplications that would likely be undetected by metaphase FISH, and ease of confirmation of suspected genomic changes by conventional FISH testing currently available in the cytogenetics laboratory. Conclusion:The array is an attractive alternative to telomere FISH and locus-specific FISH, but it does not include uniform coverage across the arms of each chromosome and is not intended to substitute for a standard karyotype.Limitations of CMA include the inability to detect both balanced chromosome changes and low levels of mosaicism.Genet Med 2005:7(6):422-432.

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confidence: 99%

Development and validation of a CGH microarray for clinical cytogenetic diagnosis

Cheung

Shaw

et al. 2005

Genetics in Medicine

237

266

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“…Schaeffer et al 35 also demonstrated the ability to pick up mosaic cell populations in a study using aCGH to examine product of conception samples. In a study using an array containing clones for the X chromosome, Veltman et al 36 showed that only half of a clone needs to be deleted in order to be detected by aCGH. In this study, we also demonstrated that for a deletion that covers only Ϸ 75% of a target clone, the mass ratio for that clone was still below 0.8.…”

Section: Polymorphismsmentioning

confidence: 99%

Detection and calibration of microdeletions and microduplications by array-based comparative genomic hybridization and its applicability to clinical genetic testing

Wong¹,

Martin²,

Heretis³

et al. 2005

Genetics in Medicine

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Purpose: Genome-wide telomere screening by fluorescence in situ hybridization (FISH) has revealed that Ϸ 6% of unexplained mental retardation is due to submicroscopic telomere imbalances. However, the use of FISH for telomere screening is labor intensive and time consuming, given that 41 telomeres are interrogated. We have evaluated the use of array-based Comparative Genomic Hybridization (aCGH) as a more efficient tool for identifying telomere rearrangements. Methods: In this study, 102 individuals with unexplained mental retardation, with either normal or abnormal FISH results, were selected for a blinded retrospective study using aCGH. Results between the two methodologies were compared to ascertain the ability of aCGH to be used in a clinical diagnostics setting. Results:We detected 100% of all imbalances previously identified by FISH (n ϭ 17) and identified two additional abnormalities, a 10q telomere duplication and an interstitial duplication of 22q11. Interphase FISH analysis verified all abnormal array results. We also demonstrated that aCGH can accurately calibrate the size of telomere imbalances by using an array with "molecular rulers" for the telomeric regions of 1p, 16p, 17p, and 22q.Conclusion: This study demonstrates that aCGH is an equivalent methodology to telomere FISH for detecting submicroscopic deletions. In addition, small duplications that are not easily visible by FISH can be accurately detected using aCGH. Because aCGH allows simultaneous interrogation of hundreds to thousands of DNA probes and is more amenable to automation, it offers an efficient and high-throughput alternative for detecting and calibrating unbalanced rearrangements, both of the telomere region, as well as other genomic locations. Genet Med 2005:7(4):264 -271.

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“…5 Here we describe a series of nine patients with monosomy 22q13 in which the size and the nature of the chromosome 22 deletions were studied in detail by highresolution chromosome-specific array-based comparative genomic hybridisation (array CGH). 7 …”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation

Koolen

Reardon

Rosser³

et al. 2005

Eur J Hum Genet

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The 22q13 deletion syndrome is associated with global developmental delay, absent or delayed speech, and generalised hypotonia. In this study, the size and nature of 22q13 deletions (n ¼ 9) were studied in detail by high-resolution chromosome specific array-based comparative genomic hybridisation (array CGH). The deletion sizes varied considerably between the different patients, that is, the largest deletion spanning 8.4 Mb with the breakpoint mapping to 22q13.2 and the smallest deletion spanning 3.3 Mb with the breakpoint mapping to 22q13.31. In one case, a unique subtelomeric 3.9 Mb deletion associated with a 2.0 Mb duplication of 22q13 was observed, adding to a growing number of similar cases identified for other chromosome ends. Remarkably, this patient had signs suggestive of retinitis pigmentosa, which has never been reported before in the 22q13 deletion syndrome. The identification of two pairs of recurrent proximal breakpoints on 22q13 suggests that these specific regions may be prone to recombination, due to yet unknown genome architectural features. In addition to the copy number changes on 22q13, a duplication of B330 kb on 22q11.1 was observed and shown to be a genetic large-scale copy number variation without clinical consequences. The current study failed to reveal relationships between the clinical features and the deletion sizes. Global developmental delay and absent or severely delayed speech were observed in all patients, whereas hypotonia was present in 89% of the cases (8/9). This study underscores the utility of array CGH for characterising the size and nature of subtelomeric deletions, such as monosomy 22q13, and underlines the considerable variability in deletion size in the 22q13 deletion syndrome regardless of the clinical phenotype.

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High resolution profiling of X chromosomal aberrations by array comparative genomic hybridisation

Cited by 51 publications

References 33 publications

Development and validation of a CGH microarray for clinical cytogenetic diagnosis

Development and validation of a CGH microarray for clinical cytogenetic diagnosis

Detection and calibration of microdeletions and microduplications by array-based comparative genomic hybridization and its applicability to clinical genetic testing

Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation

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