Interpretation. There is huge promise in discovering the genetic basis of neurodevelopmental disorders using exome sequencing, but it is often not clear how ambiguous results are communicated to families. In a recent publication in Clinical Genetics, the authors try to understand what happens to exome results as they land on the clinician’s desk – and leave us with the conclusion that diagnostic exome sequencing when reviewed in a clinical setting may have a false positive rate of up to 20% with 5% of false negatives. Continue reading
Tag Archives: exome analysis
Beneath the surface – the role of small inherited CNVs in autism
Grey zone. Structural genomic variants or copy number variations (CNV) can be reliably assessed using array comparative genomic hybridization (array CGH) or Single Nucleotide Polymorphism (SNP) arrays. However, for deletions or duplications smaller than 50-100 kB, these technologies have a poor detection rate with many false positive and false negative findings unless platforms are used that target specific candidate regions. Exome analysis, on the other hand, is capable of assessing genetic variation reliably on the single base-pair level. Between both technologies, there is a grey zone of structural genomic variants that are difficult to detect; CNVs smaller than 50 kB are often difficult to assess, and the extent and pathogenic role of these small CNVs is unclear. Now, a recent paper in the American Journal of Human Genetics manages to detect small CNVs through exome data. Their analysis in patients with autism, parents, and unaffected siblings suggests a contribution of small inherited CNVs to the overall autism risk. Continue reading
