Comparison of targeted and whole genome analysis of postnatal specimens using a commercially available array based comparative genomic hybridisation (aCGH) microarray platform

Aston, Emily; Whitby, Heidi; Maxwell, Teresa; Glaus, Natalie; Cowley, Brett C.; Lowry, D; Zhu, Xiao Lin; Issa, Bonnie; South, Sarah T.; Brothman, Arthur R.

doi:10.1136/jmg.2007.055319

Cited by 25 publications

(15 citation statements)

References 22 publications

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“…As part of our study, we detected CNCs involving multiple consecutive BAC probes in 20 out of 278 patients, which have arisen de novo and were therefore presumed to be pathogenic (Table 1) 38 . Several of these cases have been described in detail.…”

Section: Resultsmentioning

confidence: 99%

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

et al. 2009

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Section: Resultsmentioning

confidence: 99%

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

et al. 2009

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“…This is, however, expected to simultaneously reduce the number of pathogenic findings [Aston et al, 2008;Coppinger et al, 2009]. Moreover, targeted arrays do not allow for detection of new genetic syndromes.…”

Section: Clinical Relevance Of Differences In Detection Rate and Specmentioning

confidence: 99%

From Karyotyping to Array-CGH in Prenatal Diagnosis

Lichtenbelt

Knoers²,

Schuring-Blom³

2011

Cytogenet Genome Res

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Conventional karyotyping detects chromosomal anomalies in up to 35% of pregnancies with fetal ultrasound anomalies, depending on the number and type of these anomalies. Extensive experience gained in the past decades has shown that prenatal karyotyping is a robust technique which can detect the majority of germline chromosomal anomalies. For most of these anomalies the phenotype is known. In postnatal diagnosis of patients with congenital anomalies and intellectual disability, array-CGH/SNP array has become the first-tier investigation. The higher abnormality detection yield and its amenability to automation renders array-CGH also suitable for prenatal diagnosis. As both findings of unclear significance and unexpected findings may be detected, studies on the outcome of array-CGH in prenatal diagnosis were initially performed retrospectively. Recently, prospective application of array-CGH in pregnancies with ultrasound anomalies, and to a lesser extent in pregnancies referred for other reasons, was studied. Array-CGH showed an increased diagnostic yield compared to karyotyping, varying from 1–5%, depending on the reason for referral. Knowledge of the spectrum of array-CGH anomalies detected in the prenatal setting will increase rapidly in the years to come, thus facilitating pre- and posttest counseling. Meanwhile, new techniques like non-invasive prenatal diagnosis are emerging and will claim their place. In this review, we summarize the outcome of studies on prenatal array-CGH, the clinical relevance of differences in detection rate and range as compared to standard karyotyping, and reflect on the future integration of new molecular techniques in the workflow of prenatal diagnosis.

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“…The Constitutional Chip also included backbone clones to cover the rest of the genome with an interval of about 1 Mb. Since that time, more BAC clones (from 589 to Ͼ4600) have been selected to cover additional clinically relevant regions (approximately 40 -150 recognized genomic disorders/syndromes), improving detection rates from 5.6% in the first-generation BAC arrays to 10.8% in later arrays (68,73 ).…”

Section: Clinical-diagnostic Utilitymentioning

confidence: 99%

“…In general, CNVs can be categorized into 3 major groups: CNVs with established pathogenicity (pCNVs), i.e., deletions/duplications that overlap with re- (14,30,(65)(66)(67)(68)(69)(70), Table 4]. Even when bCNVs and uCNVs are intentionally avoided during array design, a large percentage of the identified imbalances often belong to bCNVs or uCNVs, because a substantial number of novel CNVs are still being discovered (Table 4).…”

Section: Understanding Cnvsmentioning

confidence: 99%

Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics

Shen

2009

Clinical Chemistry

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Background: Microarray-based genomic DNA profiling (MGDP) technologies are rapidly moving from translational research to clinical diagnostics and have revolutionized medical practices. Such technologies have shown great advantages in detecting genomic imbalances associated with genomic disorders and single-gene diseases. Content: We discuss the development and applications of the major array platforms that are being used in both academic and commercial laboratories. Although no standardized platform is expected to emerge soon, comprehensive oligonucleotide microarray platforms—both comparative genomic hybridization arrays and genotyping hybrid arrays—are rapidly becoming the methods of choice for their demonstrated analytical validity in detecting genomic imbalances, for their flexibility in incorporating customized designs and updates, and for the advantage of being easily manufactured. Copy number variants (CNVs), the form of genomic deletions/duplications detected through MGDP, are a common etiology for a variety of clinical phenotypes. The widespread distribution of CNVs poses great challenges in interpretation. A broad survey of CNVs in the healthy population, combined with the data accumulated from the patient population in clinical laboratories, will provide a better understanding of the nature of CNVs and enhance the power of identifying genetic risk factors for medical conditions. Summary: MGDP technologies for molecular diagnostics are still at an early stage but are rapidly evolving. We are in the process of extensive clinical validation and utility evaluation of different array designs and technical platforms. CNVs of currently unknown importance will be a rich source of novel discoveries.

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Comparison of targeted and whole genome analysis of postnatal specimens using a commercially available array based comparative genomic hybridisation (aCGH) microarray platform

Abstract: CGH microarray provides a likely aetiology for the clinical phenotype in many cytogenetically normal cases, and a whole genome array generally identifies copy number changes more effectively than a targeted chip alone.

Cited by 25 publications

References 22 publications

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

From Karyotyping to Array-CGH in Prenatal Diagnosis

Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics

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