Transform carrier screening research
Advances in genetic analysis tools are revolutionizing reproductive health and transforming the way carrier screening research is being conducted. Traditionally, molecular research laboratories have focused on analyzing just a few genetic changes that cause inherited diseases and are known or assumed to be associated with an individual’s ethnicity. With the identifi cation of more causative variants—both sequence and structural—and increasing ethnic diversity in certain regions, it is becoming signifi cantly important to expand carrier screening research to include more variants and diseases.
The Applied Biosystems CarrierScan Assay is an innovative, comprehensive, and high-throughput microarray-based tool for the reliable and robust detection of sequence and structural variation for preconception expanded carrier screening research across a wide range of ethnicities. The unique feature of this tool is the ability to consolidate multiple copy number and genotyping tests into a single molecular assay. With simple data analysis and reporting software included in the complete solution, high-throughput molecular labs can generate all relevant carrier screening research data quickly. The complete CarrierScan Assay solution offers flexibility and scalability to meet the changing needs of high-throughput molecular research labs, and includes the following components:
Reagents for manual or automatated sample preparation
GeneTitan MC Instrument
CarrierScan Reporter Software for data analysis and export
Consolidate multiple assays into one
To perform expanded carrier screening research efficiently and reliably, a laboratory must be able to assess a wide range of genetic changes in each sample. For example, recessively inherited complex conditions (Figure 1) such as α- and β-thalassemia can be caused by multiple types of genetic variants, including copy number deletions or duplications in either HBA1, HBA2, or both genes (α-thalassemia), and mutations in the HBB gene (β-thalassemia and sickle-cell anemia). For accurate detection of each of these variants, multiple technologies including PCR, multiplex ligation-dependent probe amplification (MLPA), sequencing, and microarrays are needed for comprehensive analysis of a single sample. This extensive requirement may limit a laboratory’s potential throughput and may increase infrastructure, maintenance, and labor costs.
Figure 1. Common genetic conditions requiring detection of both sequence and structural variants.
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All detection probes used on the CarrierScan microarray have been empirically selected based on assessment of performance in more than 1,500 samples with variants to enable highly accurate, reproducible, and robust data.
Empirical probe selection enables:
- Reduction of false calls caused by neighboring interfering variants (e.g., the delta F508 mutation on the CFTR gene)
- High true variant detection even in challenging regions of sequence homology in pseudogenes (e.g., GBA and ARSA, among others)
In addition, the most common variants have been technically and biologically verified at multiple independent locations using variant-positive samples—yielding 100% concordant results, and demonstrating excellent robustness and reproducibility. The CarrierScan Assay also offers the flexibility to analyze multiple sample types, including whole blood, tissue, cell lines, and buccal samples with a >98% pass rate.
Comprehensive coverage from the content sources you trust
The CarrierScan Assay detects approximately 6,000 sequence and structural variants in over 600 genes for 600 diseases, informed by the American College of Medical Genetics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) guidelines from well-curated, prominent databases and peer-reviewed literature [1–6]. Figure 2 shows examples of the comprehensive content offered by the CarrierScan Assay. For the CFTR gene, as an example, detection probes are included only for those mutations that are found in databases and for which relevance has been confirmed in published literature. Additionally, exon-level copy number markers are included to increase the sensitivity of the assay. Likewise, for the DMD gene, exon-level coverage is achieved with more than 12,000 empirically selected probes for reliable detection of structural variants containing deletions and duplications (del/dups). The comprehensive content also includes optional ancestry-informative markers (AIMs) for population analysis, and probes for sample identity tracking and quality assurance.
Figure 2. Examples of the comprehensive content included in the CarrierScan Assay.
Simple data analysis and reporting
Powerful biallelic and multiallelic detection, as well as state-of-the-art copy number algorithms are included in CarrierScan Reporter Software and used in conjunction with curated annotations for population frequencies, providing quick, reliable, and automated data analysis. CarrierScan Reporter Software automates the most common calculations for single and paired sample analysis for carrier screening research, making reporting simple. Export of annotations is customizable by population or panel, allowing you to filter and translate data quickly and easily into a format that meets your specific laboratory needs (Figure 3). Additionally, due to the intrinsic complexity of the SMN1 gene (spinal muscular atrophy), the included SMN Reporter Software discerns carrier states for SMN1. It provides reliable SMN1 calls, generates plots for each sample, and provides a single carrier status call that can be easily exported into a report. The combined softwares help you analyze and report data with ease.
|Hyperinsulinemic hypoglycemia, familial, 1||ABCC8||82|
|Maple syruurine disease, type IA||BCKDHA||24|
|Maple syruurine disease, type IB||BCKDHB||32|
|Maple syruurine disease, type II||DBT||9||Yes|
|Usher syndrome, type 3A||CLRN1||4|
|Dihydrolipoamide dehydrogenase deficiency||DLD||10|
|Fanconi anemia, complementation grou A||FANCA||21||Yes|
|Fanconi anemia, complementation group C||FANCC||30|
|Fanconi anemia, complementation grou G||FANCG||9|
|Glycogen storage disease type IA||G6PC||71|
|Glycogen storage disease type IB||SLC37A4<>||16|
|Sickle-cell disorders and β-thalassemia||HBB||126||Yes|
|Myeloproliferative leukemia virus oncogene||MPL||11|
|Niemann-Pick disease, type A/B||SMPD1||52|
|Joubert syndrome 2||TMEM216||7|
|Joubert syndrome 7||RPGRIP1L||2|
|Spinal muscular atrophy||SMN1||11||Yes|
- Grody WW et al. (2013) ACMG position statement on prenatal/preconception expanded carrier screening. Genet Med 15:482–483.2.
- Landrum MJ et al. (2016) ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res 44:D862–868.3.
- Stenson PD et al. (2003) Human Gene Mutation Database (HGMD): 2003 update. Hum Mutat 21:577–581.4.
- Zlotogora J et al. (2015) The Israeli national population program of genetic carrier screening for reproductive purposes. Genet Med 18:203–206.5.
- Langfelder-Schwind E et al. (2014) Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns 23:5–15.6.
- Sosnay PR et al. (2013) Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 45:1160–1167.
For Research Use Only. Not for use in diagnostic procedures.