BAC array CGH reveals genomic aberrations in idiopathic mental retardation

Miyake, Noriko; Shimokawa, Osamu; Harada, Naoki; Sosonkina, Nadia; Okubo, Aiko; Kawara, Hiroki; Okamoto, Nobuhiko; Kurosawa, Kenji; Kawame, Hiroshi; Iwakoshi, Mie; Kosho, Tomoki; Fukushima, Yoshimitsu; Makita, Yoshio; Yokoyama, Yuji; Yamagata, Takanori; Kato, Mitsuhiro; Hiraki, Yoko; Nomura, Masayo; Yoshiura, Ko Ichiro; Kishino, Tatsuya; Ohta, Tohru; Mizuguchi, Takeshi; Niikawa, Norio; Matsumoto, Naomichi

doi:10.1002/ajmg.a.31098

Cited by 62 publications

(47 citation statements)

References 20 publications

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“…In the last three years, several studies have established validity of this technique for use in MR/DD genetic testing [Shaw-Smith et al, 2004;Bradinova et al, 2005;de Vries et al, 2005;Schoumans et al, 2005;Miyake et al, 2006]. The variation in diagnostic yield reported in various studies (8.9-24%) is presumably due to differences in the ascertainment of the phenotype [Moog, 2005] and array-CGH technique.…”

Section: Introductionmentioning

confidence: 94%

An oligonucleotide based array‐CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation

Toruner

Streck²,

Schwalb

et al. 2007

American J of Med Genetics Pt A

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Developmental delay (DD) and mental retardation (MR) are important child heath issues with a one percent prevalence. Karyotyping with or without subtelomeric FISH (fluorescent in situ hybridization), unless the phenotype of the patient suggests a specific aberration for a specific FISH assay, is the most common procedure in cytogenetic evaluation of MR/DD. In addition, there are several platforms utilizing microarray based comparative genomic hybridization technology (array-CGH) for genetic testing. Array-CGH can detect deletions or duplications in very small segments of chromosomes and the use of this technology is expected to increase the diagnostic yield. The major limitation of the current BAC based array technologies is the low resolution ( approximately 1 Mb) of the chip and suboptimal coverage particularly in the subtelomeric regions. Our aim was to design a novel array-CGH chip with high-density of probes in the subtelomeric regions as well as to maintain sufficient density in other regions of the genome to provide comprehensive coverage for DD/MR. For this purpose, we used Human Genome CGH Microarray 44B chip (Agilent) as the template for the novel design. Using e-array 4.0 (Agilent), one third of the probes were randomly removed from the array and replaced by 14,000 subtelomeric probes. The average density of the probe coverage is 125 kb and 250-400 probes interrogate subtelomeric regions. To evaluate the array, we tested 15 samples (including subtelomeric aberrations and other microdeletion syndromes), which were previously analyzed by karyotyping and/or FISH. The concordance rate between array results and previous results is 100%. In addition we detected two novel aberrations that were not detected by karyotyping. These results demonstrate the utility of this format of array-CGH in detecting genome wide submicroscopic copy number changes as well as providing comprehensive coverage of all subteleomeric regions.

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Section: Introductionmentioning

confidence: 94%

An oligonucleotide based array‐CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation

Toruner

Streck²,

Schwalb

et al. 2007

American J of Med Genetics Pt A

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“…However, of the 97 patients with reproducible copy-number changes, the majority had alterations inherited from phenotypically normal parents and were, therefore, likely CNVs. Recently, Miyake et al (2006) screened 30 subjects with idiopathic mental retardation with a 1.4-Mb resolution BAC array and found chromosome abnormalities in 17%. Most patients also showed CNVs.…”

Section: Array Cgh In the Diagnostic Laboratory And Clinical Medicinementioning

confidence: 99%

Medical applications of array CGH and the transformation of clinical cytogenetics

Shaffer

Bejjani²

2006

Cytogenet Genome Res

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Microarray-based comparative genomic hybridization (array CGH) merges molecular diagnostics with traditional chromosome analysis and is transforming the field of cytogenetics. Prospective studies of individuals with developmental delay and dysmorphic features have demonstrated that array CGH has the ability to detect any genomic imbalance including deletions, duplications, aneuploidies and amplifications. Detection rates for chromosome abnormalities with array CGH range from 5–17% in individuals with normal results from prior routine cytogenetic testing. In addition, copy number variants (CNVs) were identified in all studies. These CNVs may include large-scale variation and can confound the diagnostic interpretations. Although cytogeneticists will require additional training and laboratories must become appropriately equipped, array CGH holds the promise of being the initial diagnostic tool in the identification of visible and submicroscopic chromosome abnormalities in mental retardation and other developmental disabilities.

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“…Although arrays with whole genome coverage have been produced, [5][6][7][8][9][10] the great majority of clinical cases have been analyzed on much more focused arrays, partly because of the problems of production, analysis, and interpretation of the extensive amount of data that can be generated in array experiments. 11,12 These arrays have been primarily concentrated in specific genomic regions that have either been shown to correlate with genetic disorders, or which are expected to have that potential (e.g., subtelomeric and pericentromeric regions).…”

mentioning

confidence: 99%

Bacterial artificial chromosome-emulation oligonucleotide arrays for targeted clinical array-comparative genomic hybridization analyses

Kang

Shaw

et al. 2008

Genetics in Medicine

103

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Purpose: The goal of this work was to test the ability of oligonucleotide-based arrays to reproduce the results of focused bacterial artificial chromosome (BAC)-based arrays used clinically in comparative genomic hybridization experiments to detect constitutional copy number changes in genomic DNA. Methods: Custom oligonucleotide (oligo) arrays were designed using the Agilent Technologies platform to give high-resolution coverage of regions within the genome sequence coordinates of BAC/P1 artificial chromosome (PAC) clones that had already been validated for use in previous versions of clone arrays used in clinical practice. Standard array-comparative genomic hybridization experiments, including a simultaneous blind analysis of a set of clinical samples, were conducted on both array platforms to identify copy number differences between patient samples and normal reference controls.Results: Initial experiments successfully demonstrated the capacity of oligo arrays to emulate BAC data without the need for dye-reversal comparisons. Empirical data and computational analyses of oligo response and distribution from a pilot array were used to design an optimized array of 44,000 oligos (44K). This custom 44K oligo array consists of probes localized to the genomic positions of Ͼ1400 fluorescence in situ hybridization-verified BAC/PAC clones covering more than 140 regions implicated in genetic diseases, as well as all clinically relevant subtelomeric and pericentromeric regions. Conclusions: Our data demonstrate that oligo-based arrays offer a valid alternative for focused BAC arrays. Furthermore, they have significant advantages, including better design flexibility, avoidance of repetitive sequences, manufacturing processes amenable to good manufacturing practice standards in the future, increased robustness because of an enhanced dynamic range (signal to background), and increased resolution that allows for detection of smaller regions of change. Genet Med 2008:10(4):278 -289. Key Words: array-CGH, oligonucleotide, focused microarray, CNV, chromosome abnormalities, mosaicismThe advent of array-based copy number analysis using comparative genomic hybridization (CGH) or non-CGH methods, including analysis of single nucleotide polymorphisms, has been a breakthrough in the detection of chromosomal copy number changes in the clinical setting. 1 This approach has been shown to be superior to both classical cytogenetic banding methods and fluorescence in situ hybridization (FISH)-based methods because of the greatly improved resolution and highly multiplexed nature of the method. [2][3][4] It is clear that this "molecular cytogenetic" methodology will continue to expand the capabilities for correlations between chromosomal aberrations and clinical phenotypes. This will be invaluable, not only for the diagnostic potential, but also for eventual discovery of the true genotypic basis for specific syndromic features at the molecular level.Until recently, most clinical applications of array-CGH, other than some cancer studies, have...

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BAC array CGH reveals genomic aberrations in idiopathic mental retardation

Cited by 62 publications

References 20 publications

An oligonucleotide based array‐CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation

An oligonucleotide based array‐CGH system for detection of genome wide copy number changes including subtelomeric regions for genetic evaluation of mental retardation

Medical applications of array CGH and the transformation of clinical cytogenetics

Bacterial artificial chromosome-emulation oligonucleotide arrays for targeted clinical array-comparative genomic hybridization analyses

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