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.
Today there are millions of patients suffering from misdiagnosed or undiagnosed genetic diseases as a result of insufficient genetic testing. Although in certain cases approaches like single gene testing, panel testing, or microarrays can 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 is the only test that can detect nearly all types of disease-causing genetic variants in one single test.1,2
Most studies on genetic diseases have been heavily biased towards variants in gene coding regions, but this only accounts for approx. 1-2% of a patient’s entire genome. Recently, however, a growing body of studies have demonstrated that clinical WGS offers a more comprehensive analysis than WES and can provide molecular diagnosis where WES can not.1-5 Non-coding variants, such as intergenic and intronic pathogenic variants, are growing in number and importance, spanning from sequence variants to more complex structural variations.5,6
CentoGenome®, CENTOGENE's whole genome sequencing service, offers the most comprehensive one-step solution with the highest diagnostic yield.
Why Choose CentoGenome®?
CentoGenome® – Key Features
CENTOGENE’s WGS solution, CentoGenome®, offers unparalleled genome coverage and captures one of the most extensive ranges of disease-causing genetic variants in a single test. This includes single nucleotide variants (SNVs), small insertions/deletions (InDels), and structural variants (SVs), including copy number variations (CNVs), and heteroplasmic mitochondrial variants.
CentoGenome® is a highly effective diagnostic tool - delivering high diagnostic yields across a variety of rare genetic conditions. CentoGenome® is especially valuable in patients for whom previous WES produced negative results, with a recent study showing its ability to solve up to 30% of WES negative cases.5
By choosing this comprehensive and rapid analysis, you can save your patients valuable time to diagnosis and consequently may help to further refine prognosis and enhance therapeutic decision-making.
|VARIANTS|| Reliable and sensitive detection of nearly all variant types |
Copy number deletion
*Variants with low quality and/or unclear zygosity are confirmed by an additional method.
DOWNLOADS FOR WHOLE GENOME SEQUENCING
Scientific study about Genome SequencingDownload
CentoGenome® Solo - Sample report, positiveDownload
CentoGenome® Trio - Sample report index, positiveDownload
CentoGenome® Trio - Sample report parent 1, positiveDownload
CentoGenome® Trio - Sample report parent 2, positiveDownload
When is WGS Recommended ?
WGS 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.
We recommend CentoGenome® for patients when:
- The symptoms are very broad, complex, or unspecific, not pointing towards specific disease or typical phenotype
- Clinical or genetic heterogeneity (e.g., intellectual disability/developmental delay, epilepsy, muscular dystrophies/muscular disorders, ataxia, neuropathies, cardiomyopathies, skeletal dysplasias, immunodeficiency, deafness, blindness)
- Diseases or patients with atypical clinical presentations or phenotypes (e.g., patient with intracranial aneurysm due to PKD1 gene - polycystic kidney disease)
- Patients with `blended' clinical presentations and clinical suspicion of dual diagnosis (e.g., patient with deafness and ichthyosis, intellectual disability and severe immunodeficiency)
- Suspected of a microdeletion or microduplication syndrome (e.g., patients with neurodevelopmental delay, multiple dysmorphisms and/or malformations, growth delay)
- Suspected mitochondrial disease (e.g., patient with muscular weakness, cardiomyopathy, visual problems)
- Prior testing did not provide a conclusive diagnosis
- Patient with autosomal dominant spastic paraplegia and with a negative result for the gene panel
- Patient with neurodevelopmental delay, with similarly affected siblings, and a negative testing with microarrays and WES
- Any case with suspected genetic disease and negative WES
- A fast diagnosis is a medical necessity and there is not always the time for serial testing strategies
- Patients severely ill for whom a diagnosis may direct or alter medical management (e.g., children with seizures, hypotonia, neurological abnormalities, and a rapidly deteriorating clinical status)
- Newborns, babies and children where a rapid diagnosis is crucial for prognosis and treatments decisions (e.g., critically ill newborns and children in the neonatal and pediatric intensive care NICU and PICU)
Our most recent study, where we present the largest cohort of patients with WGS performed in a clinical setting to date, demonstrated the diagnostic strength of CentoGenome® as the most comprehensive genetic test and its superiority to WES.5 The results also support that WGS should be considered the `standard of care' for genetic testing, as well as a first-line stand-alone test for rare disease patients.
CentoGenome® – Tailored Services to Your Patient's Needs
We offer flexible testing options and additional services that allow you to tailor the CentoGenome® analysis to you patient’s needs, as for example WGS for ongoing pregnancies with fetal abnormalities for prenatal diagnostics and expedited WGS for critically ill patients that need rapid and precise genetic diagnosis.
When a rapid diagnosis is a medical necessity
A rapid diagnosis can be critical for timely and appropriate medical intervention. Several recent studies demonstrate how the high diagnostic yield and short turnaround time of WGS enables improved clinical decision making in critically ill newborn infants and children in the Neonatal Intensive Care Units (NICU) or Pediatric Intensive Care Units (PICU). 7-11
CentoGenome®, with a turnaround time of down to 15 days, acts as a comprehensive and accurate tool that will potentially improve critical decision making when used as a first-line test for diagnosing critically ill newborns or children.
|OPTIONS AND ADDITIONAL SERVICES|
|TURNAROUND TIME||Regular||≤20 business days|
|Fast||≤15 business days|
|TESTING DESIGN||Solo, Duo, Trio and Trio Plus|
|ADDITIONAL SERVICES||Reanalysis and medical reinterpretation at low cost in case of uncertain or negative results|
|Prenatal with prioritization and expediting at each stage of the process* |
*Please consult our dedicated Prenatal Testing page for details
Conclusive Clinical Reports
In WGS, data analysis and identifying the disease-causing variants among a large number of variants is still a challenge. With CentoGenome®, we can help you to diagnose complex and unsolved cases by finding the clinically important variants. CentoGenome® combines our world-class experience in rare disease diagnostics, genomic testing and clinical interpretation.
We analysed tens of thousands of clinical genomes or exomes from patients worldwide. This experience and variant information is integrated and reflected in in our proprietary rare disease data repository, CentoMD®. 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
- Comprehensive data and medical interpretation by experienced professionals
- Clear results of identified variants that can explain the phenotype following international best-practice guidelines (ACMG)12,13
- Recommendations for differential diagnoses or follow-up analyses for specific diseases
- References to publications supporting the medical and scientific results
- Detailed method description
- Optional research findings related to phenotype if the diagnostic results are negative, and/or incidental findings based on ACMG guidelines.13
- CENTOGENE’s 'Tabular List' variant section, which includes known gene variants in CentoMD® that have been classified pathogenic/likely pathogenic and are linked to severe and early-onset diseases (for more information, see details and the list of genes covered).
For high-quality interpretation of the data, it is crucial to obtain specific and detailed clinical information about the patient and ideally also include further family members when performing WGS. Several studies have shown that the chances of having a clinically useful genetic result increases with the quality of the clinical information provided.5,14
REFERENCES: 1Lionel et al. 2018, PMID: 28771251; 2Sanghvi et al. 2018, PMID: 9144510; 3Clark et al. 2018; PMID: 30002876; 4Stavropoulos et al. 2016, PMID: 28567303; 5Bertoli-Avella et al. 2020, PMID: 32860008; 6Bick et al. 2019, PMID: 31023718; 7Kingsmore et al. 2019, PMID: 31564432; 8Petrikin et al. 2018, PMID: 29449963; 9Soden et al. 2014; PMID: 25473036; 10Van Diemen et al. 2017, PMID: 28939701; 11Willig et al. 2015, PMID: 25937001; 12Richards et al. 2015, PMID: 25741868; 13Kalia et al. 2017, PMID: 27854360; 14Köhler et al. 2019, PMID: 30476213
The nervous system is particularly vulnerable to genetic defects, and novel pertinent gene-disease associations are still being discovered. A recent example is the link between impaired neurodevelopment and recessive loss-of-function variants in the gene NEMF. Two of the five families that are…
Renal defects are rather common in inherited disorders, while absence of kidneys is very rare. A focused analysis of CENTOGENE’s data repository CentoMD® revealed loss-of-function mutations in GFRA1 as a novel cause for this lethal condition. These findings were published in the Journal of the…
Genetic disorders are prevalent in many developing countries, but access to genomic testing is limited. In the frame of a charity testing program, CENTOGENE has provided diagnoses for more than 200 Pakistani children over a one-year period. Of note, there were immediate steps that could be taken…