Multiple Sclerosis Genetic Risk — HLA-DRB1*15:01 is the strongest MS risk factor, but the true clinical value of genetic testing is identifying the rare monogenic white matter diseases that masquerade as MS and require completely different treatment.
Whole genome sequencing determines HLA haplotypes (DRB1*15:01 and 200+ additional MS-associated variants) and evaluates monogenic MS mimics — LMNB1, CSF1R, HTRA1 (CARASIL), NOTCH3 (CADASIL) — distinguishing true MS from treatable genetic leukodystrophies.
Multiple Sclerosis — Genetic Risk
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system affecting approximately 1 million people in the US. MS heritability is approximately 50%, with the HLA-DRB1*15:01 allele as the strongest single genetic risk factor — carrying approximately 3-fold increased risk. Over 230 common genetic variants have been identified through GWAS, collectively explaining approximately 48% of the genetic risk. Additional susceptibility genes include IL7R, IL2RA, CD58, TNFRSF1A, and IRF8.
While MS is polygenic in most patients, the most clinically important application of genetic testing in MS is the identification of rare monogenic diseases that mimic MS clinically and radiologically but have fundamentally different etiologies and treatments. CADASIL (NOTCH3) presents with white matter lesions, cognitive decline, and migraine — often misdiagnosed as MS for years. CARASIL (HTRA1) presents similarly with additional alopecia. Adult-onset leukodystrophies (LMNB1 — autosomal dominant adult-onset leukoencephalopathy with axonal spheroids, CSF1R — hereditary diffuse leukoencephalopathy with spheroids) produce progressive white matter disease indistinguishable from progressive MS on MRI.
Patients diagnosed with 'MS' who carry a monogenic white matter disease variant do NOT respond to MS disease-modifying therapies (interferon-β, natalizumab, ocrelizumab) — because their disease is not autoimmune demyelination. Continued treatment with MS therapies (which carry significant side effects including PML risk with natalizumab) without benefit is harmful. Genetic testing identifies these patients, redirecting them to appropriate management. Additionally, HLA-DRB1*15:01 status may influence MS therapy selection in future precision medicine approaches.
Monogenic MS mimics (CADASIL, CARASIL, CSF1R leukodystrophy) do NOT respond to MS therapies. Patients misdiagnosed as MS receive immunosuppressive treatments with serious risks but no benefit. Genetic testing prevents ongoing iatrogenic harm.
The primary clinical utility of genetic testing in MS is identifying the ~3-5% of 'MS' patients who actually have a genetic leukodystrophy or vasculopathy — changing treatment from harmful immunosuppression to appropriate disease-specific management.
CADASIL is misdiagnosed as MS in up to 10% of cases — years of ineffective MS therapy while the true diagnosis goes untreated
CADASIL (NOTCH3) produces periventricular and subcortical white matter lesions on MRI that can satisfy the McDonald diagnostic criteria for MS. Patients may receive MS disease-modifying therapies for years without benefit — while the CADASIL progresses with cognitive decline, recurrent strokes, and vascular dementia. NOTCH3 testing should be considered in any 'MS' patient with atypical features: prominent migraine with aura, subcortical infarcts, cognitive decline disproportionate to clinical disability, or family history of stroke/dementia. WGS identifies NOTCH3 variants alongside HLA typing and evaluation of all other white matter disease genes.
HLA-DRB1*15:01 typing may guide future precision MS therapy selection — establishing baseline genetic architecture for emerging stratified approaches
While HLA-DRB1*15:01 status does not currently change MS therapy selection, precision medicine approaches in MS are emerging. Studies suggest that HLA-DRB1*15:01 carriers may respond differently to specific disease-modifying therapies. Genome-wide polygenic risk scores for MS are in development for clinical use. Establishing a patient's complete genetic architecture through WGS provides a permanent resource for ongoing reanalysis as pharmacogenomic MS research matures — without requiring repeat testing.
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 Multiple Sclerosis — Genetic Risk 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.
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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
