aCGH for CNV analysis
Genefficiency™ aCGH Services deliver high-quality, high-throughput detection of CNVs.
Genefficiency aCGH-CNV Services utilise array comparative genomic hybridisation (aCGH), the gold-standard technology for copy number variation (CNV) analysis, to deliver high-quality data for your association study. Choose from pre-designed or custom designed arrays plus benefit from our bespoke data analysis services.
Genefficiency arrays for CNV deliver:
- The most accurate technology for identifying CNV1
- Cost-effective analysis using catalogue or custom arrays
- Exceptional study design, data analysis options and support
- Peace of mind with complete sample tracking and quality assurance
- Rapid and standardised delivery of high-quality results using automated, high-throughput sample processing
The role of CNVs in health and disease
CNVs are generally defined as inter- or intra-chromosomal duplications or deletions of segments of DNA greater than 1kb in length2. aCGH is a microarray-based technique to detect such gains or losses in DNA.
The prevalence of CNVs in the healthy population suggests that these represent a significant proportion of total genomic variation, higher than that of single nucleotide polymorphisms (SNPs). The Database of Genomic Variants (DGV) has annotated 18.8% of the euchromatic human genome as copy number variable. Most recently, it has been estimated that CNVs may affect as much as 4–5% of the human genome3. This includes inherited and de novo losses or gains in genomic sequence. A proportion of these CNVs are found in coding or regulatory regions of the genome, where they can affect expression levels of genes. As a result, these CNVs have been implicated in the pathogenesis of a growing number of diseases, including cancer4, autoimmune disease5, asthma6, schizophrenia7, and obesity8,9.
OGT’s experience in aCGH for CNV
OGT recently used its high-throughput technology to complete the completed the world's largest CNV study — generating almost 3 billion high-quality data points from >20,000 samples in 20 weeks for the Wellcome Trust Case Control Consortium (WTCCC) project.
The study used DNA samples from over 21,000 patients and controls to identify genetic variants influencing susceptibility to diseases, including tuberculosis, coronary heart disease, types 1 and 2 diabetes, rheumatoid arthritis, Crohn’s disease, bipolar disorder, autoimmune thyroid disease, ankylosing spondylitis, multiple sclerosis, breast cancer, and hypertension.
The most accurate technology for identifying CNV
Genefficiency aCGH-CNV Services are ideal for molecular genetic studies of complex diseases, for example in the areas of neuroscience and oncology. Genefficiency Services use the Agilent platform and arrays. Agilent aCGH arrays locate more chromosomal breakpoints at higher resolution, and quantify copy number changes more accurately than any other method1.
aCGH typically uses 60mer probes — which have been proven to offer superior detection sensitivity and specificity in comparison to shorter oligonucleotide probes1 — to directly and accurately detect both known and de novo CNVs.
aCGH utilises a two-colour assay, in which two DNA samples, a test and a reference, are labelled with different fluorescent dyes and then co-hybridised to the array. Dual colour fluorescence detection allows calculation of the relative intensity of both dyes, highlighting differences in copy number between the samples. The advantage of dual colour labelling is the elimination of inter-array variability, thereby ensuring tight data sets. The long oligonucleotide probes are designed to represent the whole genome and/or focussed areas within the genome, and are designed to directly detect known and de novo CNVs.
Cost-effective analysis using catalogue or custom arrays
Genefficiency aCGH-CNV Services allow you to perform in-depth analysis of specific regions of interest at your chosen resolution. Pre-designed catalogue arrays are available (Table 1), or you can explore these and other genomic regions using custom-designed arrays.
Table 1. Pre-designed OGT and Agilent CNV microarrays
|Human||4x44k, 8x60k, 2x105k, 4x180k,1x244k, 2x400k, 1x1M|
||2x105k, 4x180k, 1x244k,1x1M|
|Rat||2x105k, 4x180k, 1x244k,1x1M|
|Other (please enquire)||Please enquire|
* For more detailed information about these arrays, please contact us.
Based on your input, our expert team will design your custom array in any format required. We can design arrays against any fully or partially sequenced genome, as well as against sequencing data. Array content is selected using OGT’s proprietary Oligome™ probe database — a database of more than 24 million oligonucleotide probes designed to the latest release of the human genome. All probes are in-silico optimised and we also offer empirical validation of the entire array content, to ensure optimal performance. We will guide you in all aspects of experimental design including the array format to choose; multiple arrays on a single slide can reduce costs and increase throughput — reducing time to result. Depending on your desired level of focus you can opt for 1, 2, 4, or 8 arrays per slide for maximum flexibility (Figure 1).
Figure 1: Flexible custom array formats to suit all requirements.
Exceptional study design and support with our experienced team
Our experienced multi-disciplinary team provide a full range of expert consultation and support services to ensure you receive the highest quality data. We can advise you on all aspects of your experimental design, including sample preparation (e.g. optimal nucleic acid extraction) and custom array design, if required. In addition, through our dedicated bioinformatics team, we offer bespoke data analysis options (Figure 2).
Personalised data analysis
OGT has developed CytoSure Interpret Software for aCGH analysis in close collaboration with researchers worldwide. CytoSure Interpret Software enables the translation of aCGH data into meaningful results. It offers automated aberration detection plus a wide range of annotation tracks to help classify copy number gains and losses, and allows labs to share results and conduct internal data review processes and report generation. The Accelerate Workflow standardises data analysis for speed, consistency and reliability of data interpretation, plus it also helps to guide less experienced users — ensuring accurate, reproducible results.
In addition to our comprehensive complimentary analysis software, our dedicated bioinformatics team offer bespoke data analysis options — from simple data transfer to more demanding pathway analysis and statistics. For best results, we encourage you to discuss your data analysis requirements with us as part of the study design. This approach ensures that the experimental design and, in particular, the sample numbers and sample pairing fully support the desired analysis.
Peace of mind with complete sample tracking and quality assurance
Your samples are valuable; therefore we perform rigorous quality control (QC) and reporting strategies — from sample right through to result.
Our industry-leading LIMS records each of the >40 QC checks undertaken on each sample and allows reporting of this information in a format that suits your needs. In addition, it records full details of all reagents, consumables and equipment used allowing a 360°audit trail.
Rapid delivery of high-quality results using automated sample processing
We have a proven track record in microarray technology and services. As the world’s first Agilent High-Throughput Certified Service Provider, we combine our expertise in microarrays with Agilent’s microarray platform.
We offer a comprehensive, flexible, high-throughput microarray service for projects ranging from 1 to 1,000s of samples. State-of-the-art robotics, Laboratory Information Management Systems (LIMS) and integrated quality controls — including full ozone monitoring and control — are combined with industry-leading microarray platforms, to ensure your project is delivered on time, within budget, and to the highest standards.
Our purpose-built, state-of-the-art laboratories are based in Oxford, UK. We work under an ISO9001:2008 and ISO27001:2005 certified management system, and our microarray Genefficiency aCGH-CNV services have been accredited to ISO/IEC 17025:2005 (UKAS accredited testing laboratory no. 4593) — one of the highest accreditations attainable by an
analytical genomic services laboratory.
Contact us today to discuss your project requirements.
- Curtis, C. et al (2009) The pitfalls of platform comparison: DNA copy number array technologies assessed. BMC Genomics10, 588
- Gökçümen, O. and Lee, C. (2009) Copy number variants (CNVs) in primate species using array-based comparative genomic hybridisation. Methods 49, 18-25.
- Conrad, D.F. et al (2010) Origins and functional impact of copy number variation in the human genome. Nature 464, 704-712.
- Heim, S. and Mitelman, F. (2010) Cancer Cytogenetic. 3rd ed. John Wiley & Sons, Inc.
- Fanciulli, M. et al (2007). FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nature Genetics 39, 721-723
- Brasch-Andersen, C. et al (2004) Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers. Human Mutation 24, 208-214
- Walsh, T. et al (2008) Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science 320, 539-543
- Walters, R.G. et al (2010) A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 463, 671-675
- Bochukova, E.G. et al (2010) Large, rare chromosomal deletions associated with severe early onset obesity. Nature 463, 666-670
Quality control at Oxford Gene Technology
Specification Sheet: Genefficiency Copy Number Variation (CNV)
Array comparative genomic hybridisation (aCGH) delivers superior performance in the detection and quantification of CNVs
High quality, sensitive detection of copy number variations (CNVs) at high throughput on Agilent microarrays