A survey of undetected, clinically relevant chromosome abnormalities when replacing postnatal karyotyping by Whole Genome Sequencing.

A survey of undetected, clinically relevant chromosome abnormalities when replacing postnatal karyotyping by Whole Genome Sequencing. Eur J Med Genet. 2018 Sep 21;: Authors: Hochstenbach R, van Binsbergen E, Schuring-Blom H, Buijs A, van Amstel HKP Abstract Whole genome sequencing (WGS) holds the potential to identify pathogenic gene mutations, copy number variation, uniparental disomy and structural rearrangements in a single genetic test. With its high diagnostic yield and decreasing costs, the question arises whether WGS can serve as a single test for all referrals to diagnostic genome laboratories ("one test fits all"). Here, we provide an estimate for the proportion of clinically relevant aberrations identified by light microscopy in postnatal referrals that would go undetected by WGS. To this end, we compiled the clinically relevant abnormal findings for each of the different referral categories in our laboratory during the period 2006-2015. We assumed that WGS would be performed on 300-500 bp DNA fragments with 150-bp paired sequence reads, and that the mean genome coverage is 30x, corresponding to current practice. For the detection of chromosomal mosaicism we set minimum thresholds of 10% for monosomy and 20% for trisomy. Based on the literature we assumed that balanced Robertsonian translocations and ∼9% of other, balanced chromosome rearrangements would not be detectable because of breakpoints in sequences of repetitive ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research