Description: Copy-number variants (CNVs) are defined as gains or losses of genomic segments with a size ranging from 50-bp to million bases contributory to human genome diversity and diseases. Although genome sequencing (GS) has been introduced for CNV analysis in current studies compared with chromosomal microarray analysis (CMA), parameters such as read-amount are varied across different laboratories causing difficulties in cross-laboratory reference. In this study, by using 50 samples with high read-depth GS and clinically significant CNVs reported, we demonstrate the minimal read-amount and the most cost-effective read-length for CNV analysis is 15 million reads and 50-bp, respectively. In addition, we showed that mosaic CNVs were readily detected when the mosaic level set as 30%, while CNVs larger than 2.5-Mb were also detectable in mosaic level as low as 20%. Furthermore, by conducting a retrospective back-to-back comparison study with routine CMA for 533 prenatal, miscarriage and postnatal cases, low-pass GS provided an overall 0.8% of additional diagnostic yield of clinically significant CNVs in different referral indications. Among them, low-pass GS reported a likely pathogenic CNV with a size of 71.3-kb in a product of conception indicating the CNV detecting resolution should be set higher than 100-kb regardless of the referral indications. With its laudable diagnostic yield, low-pass GS should be recommended as the first-tier genetic test for various patients referral for routine CMA test.

Data type: Genome sequencing and assembly

Sample scope: Multiisolate

Relevance: Medical

Release date: 2020-04-08

Last updated: 2020-01-31

Data size: 745.14GB