Exome sequencing and whole genome sequencing for the detection of copy number variation

Hehir-Kwa, Jayne Y.; Pfundt, Rolph; Veltman, Joris A.

doi:10.1586/14737159.2015.1053467

Cited by 84 publications

(92 citation statements)

References 100 publications

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“…Utilization of WES data as a single comprehensive assay for both the detection of point mutations, InDels and CNVs is urgently needed (65). First, using a single method for detection of a more comprehensive set of variants facilitates the integration of the results.…”

Section: Discussionmentioning

confidence: 99%

Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort

et al. 2016

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We developed an algorithm, HMZDelFinder, that uses whole exome sequencing (WES) data to identify rare and intragenic homozygous and hemizygous (HMZ) deletions that may represent complete loss-of-function of the indicated gene. HMZDelFinder was applied to 4866 samples in the Baylor–Hopkins Center for Mendelian Genomics (BHCMG) cohort and detected 773 HMZ deletion calls (567 homozygous or 206 hemizygous) with an estimated sensitivity of 86.5% (82% for single-exonic and 88% for multi-exonic calls) and precision of 78% (53% single-exonic and 96% for multi-exonic calls). Out of 773 HMZDelFinder-detected deletion calls, 82 were subjected to array comparative genomic hybridization (aCGH) and/or breakpoint PCR and 64 were confirmed. These include 18 single-exon deletions out of which 8 were exclusively detected by HMZDelFinder and not by any of seven other CNV detection tools examined. Further investigation of the 64 validated deletion calls revealed at least 15 pathogenic HMZ deletions. Of those, 7 accounted for 17–50% of pathogenic CNVs in different disease cohorts where 7.1–11% of the molecular diagnosis solved rate was attributed to CNVs. In summary, we present an algorithm to detect rare, intragenic, single-exon deletion CNVs using WES data; this tool can be useful for disease gene discovery efforts and clinical WES analyses.

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Section: Discussionmentioning

confidence: 99%

Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort

et al. 2016

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“…First introduced to research studies, next generation sequencing (NGS) is a widely‐used method enabling high‐throughput sequencing of large proportions of genome in a rapid and cost‐effective way. Although mainly designed for detection of single nucleotide variants (SNVs) and small insertions and deletions (indels), NGS has also been efficiently used for copy number variant (CNV) detection …”

Section: Introductionmentioning

confidence: 99%

Large gene panel sequencing in clinical diagnostics—results from 501 consecutive cases

et al. 2017

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Background In addition to whole exomes, large gene panels of clinically associated genes are used as high‐throughput sequencing tests in many clinical centers, but their clinical utility has been much less investigated. Materials and Methods Here we report the results of the 501 first unselected cases for whom TruSight One panel (Illumina Inc., San Diego, California) was sequenced as a clinical diagnostic test for a variety of indications in our department. The analysis was restricted to virtual subpanels based on referral forms, where doctors were asked to list candidate genes or select one from predefined larger panels. Results A probable or definite pathogenic finding was reported in 26.3% of cases. In 238 samples for whom 1 to 9 genes were requested for analysis, the diagnostic yield was significantly higher compared to other 263 cases for whom larger subpanels were requested (31.5% vs 21.7%, respectively, P = .016). Detected mutations included single nucleotide variants, small insertions and deletions, and larger copy number variants. Out of 157 reported mutations, 67 were previously undescribed. Conclusion The clinical utility of large gene panel sequencing in the context of other genetic diagnostic tests is discussed in detail.

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“…1, 2 It is likely that in the near future, wholegenome sequencing will become the first tier test for such patients, which has the advantage of combining in a single test the identification of pathogenic mutations and imbalances. 3 These exciting developments have caused a growing need for technicians and laboratory geneticists with specialized training in molecular genetics, and a shift from the microscope to DNA sequencing and interpretation of DNA variants.…”

Section: Sirmentioning

confidence: 99%

Fading competency of cytogenetic diagnostic laboratories: the alarm bell has started to ring

et al. 2016

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Exome sequencing and whole genome sequencing for the detection of copy number variation

Cited by 84 publications

References 100 publications

Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort

Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort

Large gene panel sequencing in clinical diagnostics—results from 501 consecutive cases

Fading competency of cytogenetic diagnostic laboratories: the alarm bell has started to ring

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