|Whole exome sequencing||Whole genome sequencing||Note|
|Breda Genetics solutions||EXOME 60MB, EXOME 90MB||GENOME FULL|
|Exons (coding regions)||✓||✓||2|
|Deep intronic regions||–||✓||4|
|Power on coding regions||optimal||optimal+||8|
|Algorithmic CNV analysis||✓||✓||9|
|Patient’s raw data size||8 GB||70 GB|
|Possibility of TRIO analysis||✓||✓|
|Overall successes rate||35%||41%||10|
- EXOME 60MB: target size 48-60MB, EXOME 90MB: 91 MB.
- Exon scanning enables the detection of missense, nonsense, in-frame, fram-shist and splice mutations
- Exon (inotron scanning enables the detection of splice mutation at canonical splice ites and splice site consensus sequences.
- Deep intronic region scanning enable the detection of deep intronic splice mutations, which are rare, but possible.
- Pathogenic mutations in regulatory regions (3′-UTR and 5’UTR are infrequent, but possible for certain non-syndromic conditions – e.g. hyperlipedemia and congenital deafness). 3′-UTR and 5′-UTR are scannned in EXOME 90MB and GENOME FULL. They are not scanned in EXOME 60MB.
- Pathogenic mutations in non-coding RNAs (ncRNAs) are infrequent, but possible (e.g. dyskeratosis congenita).
- Pathogenic mutations in intergenic regions are rare infrequent but possible, especially in cis-regulatory elements (CRE) located at significant distance form the beginning of gene transcription.
- Due to technological factors related to the absence of the capturing phase, it has been found that whole genome sequencing may show increased power in the detection of variants even in regions covered by whole exome sequencing.
- Inductive large deletions/duplications testing based on calculations against a control sample pool (or even against the same sample itself in whole genome sequencing). The resolutions is mutiexonic in both cases and requires confirmation by molecular testing. WGS may be more powerful than WES in CNV testing, as it may cover deletion/duplication breakpoints, which are often outside the regions targeted by WES.
- Average values from various publications. Patient’s with a negative WES for various reasons, may be positive at WGS or WES reanalysis. Overall, cases which are negative at WES may be positive at WGS solely in at least 3% of cases.
- Many still favor whole exome sequencing in terms of cost/efficiency ratio, especially considering that 85% of pathogenic mutations are estimated to fall within genomic regions covered by whole exome sequencing. Still, whole genome sequencing enables the detection of mutations not readable by whole exome sequencing (e.g. in deep intronic regions or cis-acting regulatory elements).