Sickle Cell Disease — a single nucleotide change in HBB that reshapes red cell architecture, obstructs microcirculation, and defines a lifetime of clinical management.
Whole genome sequencing characterizes the complete HBB genotype — including compound heterozygous combinations, severity-modifying loci, and co-inherited alpha-thalassemia variants that standard carrier screens systematically miss.
Sickle Cell Disease
Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy caused by a glutamic acid-to-valine substitution at codon 6 of the beta-globin gene (HBB p.Glu7Val; rs334). This single nucleotide variant causes hemoglobin S (HbS) to polymerize under deoxygenated conditions, distorting erythrocytes into a rigid sickle shape. These deformed cells obstruct small blood vessels, triggering vaso-occlusive crises, hemolytic anemia, and progressive organ damage across nearly every system — including the spleen, kidneys, lungs, brain, and skeleton. Sickle cell disease affects approximately 300,000 newborns annually worldwide, with the highest prevalence in sub-Saharan Africa, India, and the Middle East, though it occurs across all populations.
The genotypic architecture of SCD is more complex than the classic HbSS picture. HbSC disease (HBB Glu7Val/Glu6Lys) and HbS-beta-thalassemia (HbS/beta⁰ or HbS/beta⁺) produce distinct clinical phenotypes with different severity profiles and management implications. Severity is further modulated by fetal hemoglobin (HbF) levels — influenced by variants in BCL11A, HBS1L-MYB, and the HBB locus itself — and by co-inherited alpha-thalassemia (HBA1/HBA2 deletions), which reduces HbS polymerization and is associated with milder disease. Standard two-allele carrier testing identifies the core Glu7Val variant but is not designed to report the full genotypic complexity that determines an individual's disease trajectory.
Carrier status identification before or during pregnancy is the primary use case for genetic testing in families without a prior affected member. Cascade testing in known carrier families and confirmatory genotyping for newborn screening positives are standard clinical indications. For affected patients, complete genotyping — including HbF modifier loci and co-inherited alpha-thalassemia — is increasingly recognized as relevant to predicting hydroxyurea response and informing bone marrow transplantation eligibility criteria.
HbSS, HbSC, HbS-beta⁰ thalassemia, and HbS-beta⁺ thalassemia each carry distinct clinical prognoses. HBB genotype alone does not predict severity; modifier loci and co-inherited variants are part of the complete picture.
Standard carrier testing finds the Glu7Val variant. It does not characterize the full genotype, modifier loci, or co-inherited variants that determine clinical course.
The compound heterozygous picture matters as much as carrier status
A person who inherits one HbS allele and one beta-thalassemia allele has sickle cell disease — not simply sickle cell trait. Standard two-variant carrier tests are designed to report the rs334 Glu7Val substitution but are not optimized to simultaneously characterize beta-thalassemia alleles across the full HBB gene. Whole genome sequencing reads the complete HBB coding and regulatory sequence, identifying any co-inherited beta-thalassemia variant alongside the Glu7Val allele — determining whether a carrier couple's risk is for HbSS, HbSC, HbS-beta thalassemia, or HbS trait.
HbF modifier loci and alpha-thalassemia co-inheritance are invisible to standard panels
Fetal hemoglobin level is the strongest known modifier of sickle cell disease severity. High HbF suppresses HbS polymerization, reducing vaso-occlusive events and end-organ damage. HbF levels are regulated by common variants in BCL11A (rs1427407), HBS1L-MYB intergenic region (rs28384513), and the HBB locus Xmn1 site. Co-inherited alpha-thalassemia (HBA1/HBA2 gene deletions) further modulates disease severity. None of these modifier loci are included in standard two-allele carrier screens or hemoglobinopathy panels. Whole genome sequencing captures all of them simultaneously with the primary HBB genotype.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
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Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Sickle Cell Disease and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
- Any country — including virtual groups
- Rare and common conditions covered
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One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
