CentoGenome®
Whole Genome Sequencing
Whole genome sequencing (WGS) identifies almost all changes in a patient’s DNA by sequencing both the entire protein coding and the non-coding regions of the genome. It provides for instance detailed information on the thousands of genes involved in normal growth, development, and all of the “silent” genomic regions simultaneously.
Today there are millions of patients suffering from incorrectly diagnosed or undiagnosed genetic diseases because of insufficient genetic testing. Although in certain cases approaches like single gene testing, panel testing or microarrays are able to identify the cause of a disease, these analyses are ultimately limited and can fail to reveal the full genetic cause. WGS, in contrast, overcomes such limitations and can detect all relevant variants and variant types within a single step and method.
Most research on genetic diseases has been heavily biased towards mutations in gene coding regions, but this is about only 1-2% of a patient’s entire genome. Numerous clinical studies now exist which demonstrate the critical role of non-coding sequence variants as well.
CentoGenome® – Key Features
WGS captures the broadest scope of genetic alterations causing a disease in one single test – single nucleotide variants (SNVs), small insertions and deletions (InDels), structural variants (SVs), including large copy number variations (CNVs), and thus providing the most comprehensive variant analysis.
| Key Features | ||
|---|---|---|
| Genes | 1. Whole genome 2. All non-and protein-coding regions, regulatory regions and splice sites |
|
| Coverage | 1. Almost complete and uniform coverage of the genome 2. Mean depth ~30X 3. ~99% of the genome covered at ≥10x |
|
| Variants | SNVs and InDels | 1. Sensitivity >97.6% 2. Confirmation of potentially relevant low quality SNVs and InDels by Sanger |
| SVs and CNVs | 1. Sensitivity Deletions: 51bp-1kb >70% 1kb-10kb >60% Copy number deletion >10kb >70% Insertions: 51bp - 99bp >70% 100bp - 199bp >80% 200bp - 299 bp >75% >300 bp >65% Duplications: Tandem Duplication 100kb – 1kb >85% Tandem Duplication 1kb – 10 kb >65% Copy number duplication >10 kb >70% 2. Confirmation of unclear SVs and CNVs by an orthogonal method |
|
When is CentoGenome® Recommended?
CentoGenome® is recommended especially for the diagnosis of patients with heterogeneous phenotypes, unclear or atypical clinical symptoms, or with a long list of prior differential diagnoses, or who have exhausted other genetic testing options.
| S. No | Medical Indications | Examples |
|---|---|---|
| 1 | Clinical or genetic heterogeneity Genetic diseases with similar presentation related to many causal genes: similar phenotype – many genes |
1. Intellectual disability/ development delay Epilepsy, Epileptic encephalopathies 2. Muscular dystrophies/muscular disorder, Ataxia, Neuropathies 3. Cardiomyopathies, Skeletal dysplasias Immunodeficiency, Deafness, Blindness |
| 2 | Diseases or patients with atypical clinical presentations or phenotypes From the clinical perspective it is difficult to select a specific gene or group of genes | Patient with intracranial aneurysm (due to PKD1 gene – polycystic kidney disease) |
| 3 | Patients with ‘blended’ clinical presentations and clinical suspicion of dual diagnosis These cases also pose a challenge in the interpretation of the results |
1. Patient with deafness and ichthyosis 2. Patient with intellectual disability and severe immunodeficiency |
| 4 | Patients with clear genetic disease and previous genetic testing is negative | 1. Patient with autosomal dominant spastic paraplegia and with a negative result for the gene panel 2. Index patient with neurodevelopmental delay and 2 similarly affected siblings, CMA, WES are negative |
| 5 | Suspected of a microdeletion or microduplication syndrome | Patients with neurodevelopmental delay multiple dysmorphisms and/or malformations, and growth delay (IUGR, FTT) |
| 6 | Suspected mitochondrial disease | Patient with muscular weakness, cardiomyopathy, visual problems |
| 7 | Previous WES testing is negative | Any case with suspected genetic disease and negative WES |
| 8 | Patients and families with relevant geneticburden and want to have cutting-edge science to pursue genetic diagnosis, offering the most complete genetic test. | Patient of Index with neurogenerative disease, and 2 siblings deceased in early infancy due to same phenotype |
Clinical Anamnesis and Reporting
Conclusive clinical reports
In WGS, data analysis and identifying the disease-underlying variant(s) among a large number of variants is still a challenge. With CentoGenome®, we can help you to diagnose complex and unsolved cases of genetic origin, by finding the clinically important variants. CentoGenome® combines our expertise in bioinformatics and clinical interpretation, with our proprietary variant database CentoMD® and world-class experience in rare disease diagnostics.
We analysed tens of thousands of clinical genomes or exomes from patients worldwide. This experience and variant information is integrated and reflected in CentoMD®, which is the largest mutation database of rare genetic diseases. In combination with a solid anamnesis and description of symptoms, this is the foundation of our high diagnostic rates.
- Detailed evaluation of patient’s clinical information and family history
- Clear results of identified variants that can explain the phenotype
- Variant classification following international best-practice guidelines (ACMG)
- Comprehensive medical interpretation
- Recommendations for differential diagnoses or follow-up analyses for specific diseases
- References to publications supporting the medical and scientific results.
- Detailed description of the genetic testing method, and coverage report of genes
- Report of research variants or incidental findings (optional)
Clinical anamnesis
For high-quality interpretation of the data, it is crucial to obtain specific and detailed clinical information about the index patient and ideally also further family members when performing whole genome sequencing. This can increase the diagnostic yield to significantly over 40%.
Incidental findings
CENTOGENE does report on findings not directly related to the cause of a disease only upon request and only for genes listed in the ACMG guidelines.
