Detection and interpretation of genomic structural variation in health and disease

Vandeweyer, Geert; Kooy, R. Frank

doi:10.1586/erm.12.119

Cited by 13 publications

(6 citation statements)

References 222 publications

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“…Despite amazing progress in the past decade, the technologies and analytical approaches for sequencing and interpreting genomes still have significant blind spots, such as the greater difficulty of detecting structural variants including insertions, deletions, inversions, and trinucleotide repeat expansions, compared to single nucleotide variants in sequences [ 21 ]. Reference databases of sequence variants also contain many artifactual annotations, such as ‘variants’ that are actually sequences derived from pseudogenes similar to the gene in question.…”

Section: Research Experiments Clinical Testing and Genomic Testinmentioning

confidence: 99%

A Balanced Look at the Implications of Genomic (and Other “Omics”) Testing for Disease Diagnosis and Clinical Care

Boyd

Galli

Schrijver

et al. 2014

Genes

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The tremendous increase in DNA sequencing capacity arising from the commercialization of “next generation” instruments has opened the door to innumerable routes of investigation in basic and translational medical science. It enables very large data sets to be gathered, whose interpretation and conversion into useful knowledge is only beginning. A challenge for modern healthcare systems and academic medical centers is to apply these new methods for the diagnosis of disease and the management of patient care without unnecessary delay, but also with appropriate evaluation of the quality of data and interpretation, as well as the clinical value of the insights gained. Most critically, the standards applied for evaluating these new laboratory data and ensuring that the results and their significance are clearly communicated to patients and their caregivers should be at least as rigorous as those applied to other kinds of medical tests. Here, we present an overview of conceptual and practical issues to be considered in planning for the integration of genomic methods or, in principle, any other type of “omics” testing into clinical care.

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Section: Research Experiments Clinical Testing and Genomic Testinmentioning

confidence: 99%

A Balanced Look at the Implications of Genomic (and Other “Omics”) Testing for Disease Diagnosis and Clinical Care

Boyd

Galli

Schrijver

et al. 2014

Genes

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“…As patients with GDD/ID seldom reproduce, large pedigrees are rare. This scarcity of data has created a bias for de novo genetic causes (Vandeweyer & Kooy, 2013).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic approach with genetic tests for global developmental delay and/or intellectual disability: Single tertiary center experience

Han

Jang

Park

et al. 2018

Annals of Human Genetics

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The child with global developmental delay (GDD)/intellectual disability (ID) is deserving of the appropriate evaluation available for improving the health and wellbeing of patients and their families. To better elucidate the diagnostic approach of genetic tests for patients with GDD and/or ID, we evaluated the results in a cohort of 75 patients with clinical features of GDD and/or ID who were referred for diagnostic workup. A total of 75 children were investigated for GDD or ID in the pediatric neurology department. Ten patients (13%, 10/75) with a clinically recognizable syndrome were diagnosed by single-gene analysis. Next, chromosomal microarray was performed as a first-tier test, and 25 patients (33%, 25/75) showed structural abnormalities. Then, two fragile X syndrome (3%, 2/75) were confirmed by FMR1 gene fragment analysis. Thirty-eight remaining patients received a gene panel by nextgeneration sequencing. Eight patients were found to have an underlying genetic etiology: CHD8, ZDHHC9, MBD5, CACNA1H, SMARCB1, FOXP1, NSD1, and PAX6. As a result, 45 patients (60%, 45/75) had been diagnosed by genetic tests. Among 30 undiagnosed patients, brain structural abnormalities related to GDD/ID were observed in eight patients (11%, 8/75). However, in 22 patients (29%, 22/75), the causes of GDD/ID remained uncertain. A genetic diagnostic approach of GDD/ID by sequential molecular analysis can help in the planning of treatment, assigning the risk of occurrence in siblings, and providing emotional relief for the family. K E Y W O R D Schromosomal microarray, diagnostic approach, global developmental delay, intellectual disability, nextgeneration sequencing

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“…Next generation sequencing (NGS) has the power to screen a whole genome for all kinds of genetic variation in a single experiment [ 1 ]. In medical genetics, NGS has proven to be a key tool to identify disease-causing mutations in individuals with Mendelian disorders.…”

Section: Introductionmentioning

confidence: 99%

VariantDB: a flexible annotation and filtering portal for next generation sequencing data

et al. 2014

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Interpretation of the multitude of variants obtained from next generation sequencing (NGS) is labor intensive and complex. Web-based interfaces such as Galaxy streamline the generation of variant lists but lack flexibility in the downstream annotation and filtering that are necessary to identify causative variants in medical genomics. To this end, we built VariantDB, a web-based interactive annotation and filtering platform that automatically annotates variants with allele frequencies, functional impact, pathogenicity predictions and pathway information. VariantDB allows filtering by all annotations, under dominant, recessive or de novo inheritance models and is freely available at http://www.biomina.be/app/variantdb/.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0074-6) contains supplementary material, which is available to authorized users.

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Detection and interpretation of genomic structural variation in health and disease

Cited by 13 publications

References 222 publications

A Balanced Look at the Implications of Genomic (and Other “Omics”) Testing for Disease Diagnosis and Clinical Care

A Balanced Look at the Implications of Genomic (and Other “Omics”) Testing for Disease Diagnosis and Clinical Care

Diagnostic approach with genetic tests for global developmental delay and/or intellectual disability: Single tertiary center experience

VariantDB: a flexible annotation and filtering portal for next generation sequencing data

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