Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders

Stobbe, Gary; Liu, Yajuan; Wu, Rebecca; Hudgings, Laura Heath; Thompson, Owen; Hisama, Fuki M.

doi:10.1038/gim.2013.78

Cited by 20 publications

(20 citation statements)

References 39 publications

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“…Having technologies available for the reliable and accurate detection and characterisation of CNVs in a given human genome is highly relevant for both clinical diagnostics and basic research. Microarray-based CNV analysis has become a first-tier clinical cytogenetics procedure in patients with unexplained developmental delay/intellectual disability,15 autism spectrum disorder,16 multiple congenital anomalies17 and cancer 13 14…”

Section: Introductionmentioning

confidence: 99%

Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis

Zhou

Zhang

et al. 2018

J Med Genet

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Section: Introductionmentioning

confidence: 99%

Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis

Zhou

Zhang

et al. 2018

J Med Genet

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“…For example, a review of 33 published studies by The International Standard Cytogenomic Array Consortium (ISCA) showed that ~12% of NDD cases can be explained by a CNV 7 . The clinical yield for autism spectrum disorders (ASD) in recent studies shows that at least 5-15% of cases can be explained by CNVs that are either de novo or rare inherited in nature 8-10 . Since most characterized penetrant CNVs are inherently rare, population scale analyses are often required to assess relative disease risk and to elucidate the potential etiologic role of genetic events currently classified as “variants of unknown significance” (or VOUS) 7 .…”

Section: Introductionmentioning

confidence: 99%

“…The detection of CNVs in the clinical diagnostic setting is now largely based on an initial scan of the genome using microarrays to search for unbalanced alterations 7,9,10 . Locus, gene, and even exon-specific quantitative assays are also now used when a specific hypothesis is being pursued (e.g.…”

Section: Introductionmentioning

confidence: 99%

A high-resolution copy-number variation resource for clinical and population genetics

Uddin

Thiruvahindrapuram

Walker

et al. 2015

Genetics in Medicine

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Purpose Chromosomal microarray analysis to assess copy number variation (CNV) has become a first tier genetic diagnostic test for individuals with unexplained neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA). Over 100 cytogenetic labs worldwide use the new ultra-high resolution Affymetrix CytoScan-HD array to genotype hundreds of thousands of samples per year. Our aim was to develop a CNV resource from a new population sample, which would enable more accurate interpretation of clinical genetics data on this microarray platform, and others. Methods Genotyping of 1,000 adult volunteers who are broadly representative of the Ontario population (as obtained from the Ontario Population Genomics Platform) was performed with the CytoScan-HD microarray system, which has 2.7 million probes. Four independent algorithms were applied to detect CNVs. Reproducibility and validation metrics were quantified using sample replicates and quantitative-PCR, respectively. Results DNA from 873 individuals passed quality control and we identified 71,178 CNVs (81 CNVs/individual); 9.8% (6,984) of these CNVs were previously unreported. After applying three layers of filtering criteria, from our highest confidence CNVs dataset we obtained >95% reproducibility and >90% validation rate (73% of these CNVs overlapped at least one gene). Conclusion The genotype data and annotated CNVs for this largely Caucasian population will represent a valuable public resource enabling clinical genetics research and diagnostics.

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“…Through this technique of chromosomal microarray (CMA), numerous submicroscopic copy number variations (CNVs) throughout the genome have been identified in individuals with ASD [46]. Numerous studies have consistently demonstrated a diagnostic yield of at least 7 % with CMA in pediatric and adult cohorts with ASD, much higher than conventional cytogenetic approaches such as karyotype and FISH [47][48][49][50][51][52][53][54]. This higher yield forms the basis for recommending CMA as the first-tier genetic diagnostic test for non-specific cases of ASD [48, 55 •…”

Section: Chromosomal Aberrationsmentioning

confidence: 99%

Advances in Genetic Diagnosis of Autism Spectrum Disorders

Shen

Miller

2014

Curr Pediatr Rep

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Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental abnormalities characterized by stereotypical communicative and social impairments, affecting 1 in 88 children in the United States. Both genetic and environmental factors contribute to the etiology of ASD. Autistic traits may be part of features associated with certain syndromes or the sole clinical presentation. Due to extreme heterogeneity and variable expressivity of the condition, clinical diagnosis and management have been challenging. Major advances in genomic technologies, computing power, and bioinformatics analyses have resulted in the accelerated discovery of novel genes and risk loci associated with both inherited and sporadic forms of ASD. Pathogenic genetic defects related to ASD range from single nucleotide variation to gross chromosomal abnormalities. In this review, we first summarize the current understanding of the genetic etiology of ASD; we then discuss how genetic diagnostics may influence the management and genetic counseling of ASD; and finally, we outline the strategy to integrate genetic tests into clinical care of children with ASD. We hope to inform primary care pediatricians and clinical genetic specialists how recent advances in the genetic research of ASD have been translated into clinical genetic testing for patients.

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Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders

Cited by 20 publications

References 39 publications

Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis

Whole-genome sequencing analysis of CNV using low-coverage and paired-end strategies is efficient and outperforms array-based CNV analysis

A high-resolution copy-number variation resource for clinical and population genetics

Advances in Genetic Diagnosis of Autism Spectrum Disorders

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