Advanced Genetic Disease Research


Digital PCR Enables Breakthroughs in Quantitation and Monitoring

Genetic conditions impact lives in many different ways. From congenital anomalies such as spinal muscular atrophy (SMA) to drug-resistances that develop during chemotherapy, identifying the genetic cause can facilitate early intervention and better outcomes.

Digital PCR (dPCR) provides a quantitative approach to identifying gene deletions, copy number variations (CNVs), single nucleotide polymorphisms (SNPs), and more. Additionally, the sensitivity provided by dPCR makes the technique ideally suited for applications in cell-free fetal DNA (cffDNA) and graft-derived cell-free DNA (GcfDNA).

Quantifying Severity of Spinal Muscular Atrophy​

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. The disease is largely caused by the loss of the SMN1 gene. A duplicate gene – SMN2 – has been found to produce partial function. The presence of SMN2 can partially compensate for the loss of SMN1 and reduce disease severity.

Leveraging digital PCR’s unparalleled accuracy in quantifying copy number variation (CNV), Combinati developed the first 4-plex dPCR assay to measure SMN1, SMN2 and total SMN using the RPPH1 gene as reference. The assay was validated using 15 clinical samples including a 5cp SMN2 sample.

Measuring Allelic Imbalance with Accuracy and Ease​

Measuring Allelic Imbalance with Accuracy and Ease​

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Like in other cancers, disease-associated SNPs might be preferentially retained and could be associated with disease severity. Preferential allelic imbalance (PAI) can be measured using sequencing or traditional genotyping, but these methods often cannot provide a quantitative output. Digital PCR overcomes these limitations to provide an accurate and quantitative measurement.

Cost Effective Alternative Solution for NIPS​

Cell-free fetal DNA (cffDNA) has enabled the non-invasive detection of fetal chromosomal abnormalities in the mother’s blood. Although sequencing has been traditionally used for NIPT, digital PCR has made significant strides in recent years and could prove to be a cost-effective alternative.

Combinati, along with Atila Biosystems, has developed a 4-plex digital PCR assay that simultaneously detects for trisomies 13, 18 and 21 using chromosome 1 as the reference. By pooling 6 units for a total of 120,000 partitions, the assay is capable of detecting down fetal fraction down to 4%.

Cost Effective Alternative Solution for NIPS​
Sensitive Detection of Transplant Donor-Derived Cell Free DNA​

Sensitive Detection of Transplant Donor-Derived Cell Free DNA

Molecular monitoring of patients who receive transplants can help predict negative outcomes such as graft rejection or graft vs host disease.1 Sensitive detection of donor-derived circulating cell free DNA (ccfDNA) can help to intervene early and improve patient outcome.

With exceptionally low dead volume and best-in class accuracy, the Absolute Q dPCR platform is perfectly suited for sensitive detection of ccfDNA.

  1. Gyger M, Baron C, Forest L, Lussier P, Lagacé F, Bissonnette I, Bélanger R, Bonny Y, Busque L, Roy DC, Perreault C. Quantitative assessment of hematopoietic chimerism after allogeneic bone marrow transplantation has predictive value for the occurrence of irreversible graft failure and graft-vs.-host disease. Exp Hematol. 1998 May;26(5):426-34. PMID: 9590660.

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