Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics

Shen, Yiping; Wu, Bai-Lin

doi:10.1373/clinchem.2008.112821

Cited by 53 publications

(29 citation statements)

References 72 publications

(62 reference statements)

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“…In recent years, recurrent copy number variations identified by microarray-based genomic profiling technologies in both research and diagnostic settings have led to the increasing emergence and characterization of novel genomic imbalance disorders [Slavotinek, 2008;Mefford and Eichler, 2009;Shen and Wu, 2009]. Most of these novel recurrent genomic imbalances are structurally associated with segmental duplications, are the results of unequal crossover via a non-allelic homologous recombination mechanism, and are clinically associated with intellectual disability, autism spectrum disorders (ASD) and other developmental/neuropsychiatric disorders [Marshall et al, 2008;Stefansson et al, 2008;Mefford and Eichler, 2009].…”

Section: Introductionmentioning

confidence: 99%

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

et al. 2010

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The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion.

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Section: Introductionmentioning

confidence: 99%

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

et al. 2010

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“…The detection and analysis of CNVs has been greatly facilitated by the development of high-resolution array comparative genomic hybridization (or aCGH) and SNP (single nucleotide polymorphism) microarray technologies [118,119]. These array-based methods are now being used in the clinic to identify the sources of idiopathic diseases [120][121][122][123][124] and are the main technologies used to identify CNVs.…”

Section: Copy Number Variantsmentioning

confidence: 99%

Approaches for identifying germ cell mutagens: Report of the 2013 IWGT workshop on germ cell assays☆

Yauk

Aardema

Benthem

et al. 2015

Mutation Research/Genetic Toxicology and Environmental Mutagene

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This workshop reviewed the current science to inform and recommend the best evidence-based approaches on the use of germ cell genotoxicity tests. The workshop questions and key outcomes were as follows. (1) Do genotoxicity and mutagenicity assays in somatic cells predict germ cell effects? Limited data suggest that somatic cell tests detect most germ cell mutagens, but there are strong concerns that dictate caution in drawing conclusions. (2) Should germ cell tests be done, and when? If there is evidence that a chemical or its metabolite(s) will not reach target germ cells or gonadal tissue, it is not necessary to conduct germ cell tests, notwithstanding somatic outcomes. However, it was recommended that negative somatic cell mutagens with clear evidence for gonadal exposure and evidence of toxicity in germ cells could be considered for germ cell mutagenicity testing. For somatic mutagens that are known to reach the gonadal compartments and expose germ cells, the chemical could be assumed to be a germ cell mutagen without further testing. Nevertheless, germ cell mutagenicity testing would be needed for quantitative risk assessment. (3) What new assays should be implemented and how? There is an immediate need for research on the application of whole genome sequencing in heritable mutation analysis in humans and animals, and integration of germ cell assays with somatic cell genotoxicity tests. Focus should be on environmental exposures that can cause de novo mutations, particularly newly recognized types of genomic changes. Mutational events, which may occur by exposure of germ cells during embryonic development, should also be investigated. Finally, where there are indications of germ cell toxicity in repeat dose or reproductive toxicology tests, consideration should be given to leveraging those studies to inform of possible germ cell genotoxicity.

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“…While digital PCR is currently used for primarily quantifying DNA and analyzing copy-number variations, multiplexed digital detection is on the horizon [25], as are isothermal digital PCR systems [26]. In contrast to these PCR technologies, microarrays interrogate hundreds to millions of genetic signatures across multiple genes in a homogenous assay, and have therefore emerged as a potentially useful diagnostic platform when sample or total nucleic acid concentration is limiting [2,27,28,29,30,31]).…”

Section: Introductionmentioning

confidence: 99%

Integrated Amplification Microarrays for Infectious Disease Diagnostics

et al. 2012

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This overview describes microarray-based tests that combine solution-phase amplification chemistry and microarray hybridization within a single microfluidic chamber. The integrated biochemical approach improves microarray workflow for diagnostic applications by reducing the number of steps and minimizing the potential for sample or amplicon cross-contamination. Examples described herein illustrate a basic, integrated approach for DNA and RNA genomes, and a simple consumable architecture for incorporating wash steps while retaining an entirely closed system. It is anticipated that integrated microarray biochemistry will provide an opportunity to significantly reduce the complexity and cost of microarray consumables, equipment, and workflow, which in turn will enable a broader spectrum of users to exploit the intrinsic multiplexing power of microarrays for infectious disease diagnostics.

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Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics

Cited by 53 publications

References 72 publications

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

Intra-family phenotypic heterogeneity of 16p11.2 deletion carriers in a three-generation Chinese family

Approaches for identifying germ cell mutagens: Report of the 2013 IWGT workshop on germ cell assays☆

Integrated Amplification Microarrays for Infectious Disease Diagnostics

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