Integrated solutions for the genomic study of inherited disease

Tuesday 2 May 2017
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Genetic alterations in inherited disorders

Profiling a range of mutations, from large chromosomal rearrangements to single-exon duplications and point mutations, is integral to solving the puzzle of rare disease, and contributes to the long-term aim of improving the lives of rare disease patients. No single technology is suitable for profiling every type of genetic aberration — instead, researchers can develop a more complete picture of genomic variation by utilising a range of technologies in parallel.

Oxford Gene Technology (OGT) offers an integrated portfolio of products providing clinical researchers with the most advanced tools available to study inherited disease.

Our class-leading products are designed for the robust identification of the whole range of genomic variation, with an emphasis on custom solutions to target the regions important for your research.

  • CytoSure™ array products and custom arrays
  • SureSeq™ Next Generation Sequencing (NGS) panels and myPanel™ custom panels
  • Cytocell® microdeletion fluorescence in-situ hybridisation (FISH) probes

CytoSure array products and custom arrays

 

 

 

 

Exon-focused array design

A vital aspect of clinical genetics research is the accurate and reliable detection of CNV, for which microarray remains the gold standard. However, even the highest density microarrays are limited by the design and quantity of probes which can be used to detect CNV. By focusing expertly-designed probes to the regions being studied, ultra-high density can be achieved, enabling researchers to concentrate on the genes that matter and reliably detect even single-exon CNV.

CytoSure oligo array comparative genomic hybridisation (aCGH) products leverage OGT’s expert probe design to enable superior CNV resolution to other platforms, detecting microdeletions and microduplications at exon-level resolution across a wide range of disorders.

A deletion of 1.17kb is called across two exons from the HDAC8 geneFigure 1. A deletion of 1.17kb (minimum) is called across two exons from the HDAC8 gene, using the CytoSure Constitutional v3 8x60k array (image courtesy of Dominic McMullan, West Midlands Regional Genetics Laboratory, UK).

...it is evident that the OGT platform alone would detect the aberration... Dominic McMullan, West Midlands Regional Genetics Laboratory, UK

OGT’s microarray design expertise allows for superior CNV resolution

Figure 2. OGT’s microarray design expertise allows for superior CNV resolution

A comprehensive range of arrays for inherited disease research

CytoSure Constitutional v3 and CytoSure Constitutional v3 +LOH arrays

CytoSure Constitutional v3 arrays offer enhanced exon-level coverage of developmental disorder genes. They combine the most up-to-date and relevant developmental delay content from the recent Deciphering Developmental Disorders1 and latest updates from ClinGen the Clinical Genome Resource2. Choose from:

Top priority genes Medium priority genes Lower priority genes Decipher Syndrome regions ClinGen regions High priority backbone resolution Medium priority backbone resolution Low priority backbone resolution
CytoSure Constitutional v3 (8x60k) Exon targeted Whole gene-targeted Whole gene-targeted Whole gene-targeted Whole gene-targeted 189kb (1 probe every ~63kb) 375kb (1 probe every ~125kb) 663kb (1 probe every ~221kb)
CytoSure Constitutional v3 (4x180k) Exon targeted Exon targeted Exon targeted Whole gene-targeted Whole gene-targeted 68kb (1 probe every ~22kb) 74kb (1 probe every ~24kb) 162kb (1 probe every ~54kb)
CytoSure Constitutional v3 +LOH (4x180k) Exon targeted Whole gene-targeted Whole gene-targeted Whole gene-targeted Whole gene-targeted 68kb (1 probe every ~22kb) 74kb (1 probe every ~24kb) 162kb (1 probe every ~54kb)

Table 1. An informed, sophisticated approach to array design has been used with CytoSure v3 arrays, with more probes being located in regions of the genome that are most likely to detect a relevant aberration.

CytoSure customisable rare disease arrays

Advance your research though rapid detection of microdeletions and microduplications at exon-level resolution across a range of molecular disorders (including autism, epilepsy, neuromuscular disorders, cardiomyopathies and eye disease) using highly sensitive, customisable, exon-focused CytoSure molecular arrays. Choose from:

  • The Medical Research Exome array — containing probes targeting over 128,000 exons in 4645 genes
  • Disease Focused Research arrays — targeting genes grouped by specific disease areas
  • Customised arrays — targeting your choice of content suitable for your application and workflows

Use existing rare disease array designs or pick and choose content relevant to you and customise your ownFigure 3. Use existing rare disease array designs or pick and choose content relevant to you and customise your own

Custom arrays

Work with the world leaders in microarray design

OGT has designed hundreds of custom arrays for some of the world’s leading researchers. Ensure complete confidence in your design by leveraging OGT’s customisation service and comprehensive database of oligonucleotide probes.

  • Take advantage of our unique, tried-and-tested probe design pipeline for any application area
  • Pick and choose probes from existing arrays, our Oligome database or de novo designed
  • Flexible array formats offer different options to suit your workflow

OGT’s proprietary Oligome™ database contains more than 26 million oligonucleotide probes designed to the latest release of the human genome, either in silico or empirically optimised, to ensure the highest possible performance and minimum noise.

The ability to work closely with the OGT design team was a great advantage for us. Tracey Lewis, ARUP Laboratories, USA

Data analysis

CytoSure Interpret Software

CytoSure Interpret Software is a powerful and easy-to-use package for the analysis of aCGH data, offering an impressive combination of features that allows you the choice of standardised data analysis (using the “Accelerate Workflow”) or customised, user-defined data analysis. Additional functionality allows effortless identification of both copy number variation (CNV) and loss of heterozygosity (LOH). CytoSure Interpret Software is exclusively provided with OGT’s CytoSure aCGH arrays.

CytoSure Interpret Software enables easy and accurate detection of aberrations and breakpoints

Figure 4. CytoSure Interpret Software enables easy and accurate detection of aberrations and breakpoints. Shown here is a 130kb amplification found using an OGT 8x60k Constitutional array – a fully customisable selection of tracks simplifies interpretation.

For more information on the full list of CytoSure products visit the Array products section of our website

SureSeq NGS products

 

 

 

 

 

Next Generation Sequencing Products

NGS is a powerful technique for accurately analysing sequence-level information. The advent of targeted sequencing approaches, with their associated cost, time and analysis advantages, are further increasing the adoption of NGS in the clinical research lab. Utilising hybridisation-based enrichment, SureSeq NGS myPanel custom panels offer flexibility and deliver unmatched uniformity of coverage, allowing confident detection of inherited variants – including CNV – in targeted regions.

SureSeq myPanel NGS custom FH panel

The SureSeq myPanel NGS custom FH panel delivers:

  • Hybridisation-based enrichment for unparalleled coverage, completeness and uniformity
  • Detection of CNV as well as SNV with a single assay
  • Pre-optimised panels to reduce assay development time
  • Bespoke panel content — sequence only what’s relevant for your research, increase throughput and save on sequencing reagents

The ability to call CNV from the NGS data as well as point mutations is extremely valuable to us. Mafalda Bourbon, INSA, Portugal

CNVs in LDLR gene shown using IGV from the Broad Institute

Figure 5. CNVs in LDLR gene shown using IGV from the Broad Institute: Green bars indicate areas of CNV (data from aCGH), purple bars represent deleted exons (data from NGS): 5 samples are shown, each with at least one area of CNV. Samples provided by Malfalda Bourbon, INSA, Portugal.

All exons*

LDLR PCSK9 APOB LDLRAP1 APOE LIPA STAP1

 

Hotspots*

rs2306283 (SLCO1B1) rs4149056 (SLCO1B1)
rs11220462 (Intronic region of ST3GAL4) rs1564348 (Intronic region of SLC22A1)
rs1800562 (coding region on HFE) rs2479409 (upstream of PCSK9)
rs3757354 (~2kb upstream of MYLIP) rs4299376 (Intronic region of ABCG8)
rs629301 (3’ UTR of CELSR2) rs6511720 (Intronic region on LDLR)
rs8017377 (coding region of NYNRIN) rs1367117 (coding region of APOB)
rs429358 (coding region of APOE) rs7412 (coding region of APOE)

* Some genes/hotspots may not be available in your region - contact us for more details

Table 2. Choose your custom FH panel from optimised content to enable analysis of both SNV and CNV from a single assay

SureSeq Library Preparation Kit

With fewer hands-on steps, the SureSeq Library Preparation Kit saves an entire day from the typical library preparation workflow and reduces the potential for handling errors. Extensive optimisation of enzymes and buffers has enabled the number of steps to be reduced over standard methods, while still delivering libraries of the highest quality.

SureSeq Interpret Software

OGT’s powerful, stand-alone data analysis package — is provided free-of-charge with every SureSeq NGS Panel and allows the conversion of FASTQ files into an intuitive interactive report. The user-friendly report makes it easy to set up complex filtering rules with multiple parameters and browse CNV results with visualisation of data in IGV.

SureSeq myPanel workflowFigure 6. SureSeq myPanel Custom NGS panels allow flexibility in design without compromising on cost or quality.

For more information on the full list of SureSeq products visit the NGS products section of our website

Cytocell FISH Probes

 

 

 

 

FISH probes for inherited disorders

Fluorescence in situ hybridisation (FISH) is a cost effective, quick and highly efficient technique that can be used routinely for the precise diagnosis of inherited disorders.

The Cytocell range of high-quality FISH probes includes probes for a number of developmental delay disorders used in both pre-natal and post-natal testing. Cytocell FISH probes include a range of CE-IVD marked FAST probes that facilitate rapid diagnosis – crucial in a pre-natal setting when important
medical decisions need to be made.

Cytocell FISH probes deliver:

  • Exceptional value without compromising on performance
  • Bright signals with minimal background for fast and accurate scoring with low retest rates
  • Cost-effective formats to suit your throughput requirements
  • Excellent customer service and support in over 60 countries
  • Convenient, directly labelled products premixed in hybridisation solution

Cytocell probes provide strong signals for fast and
accurate scoring, for example in DiGeorge syndrome

Figure 7. Cytocell probes provide strong signals for fast and accurate scoring, for example in DiGeorge syndrome.

OGT’s Cytocell microdeletion probes include:

  • Alagille (JAG1)
  • Angelman (UBE3A/D15S10)
  • CHARGE
  • Cri-du-chat and Sotos Probe Combination
  • DiGeorge II (10p14)
  • DiGeorge and 22q13.3 Deletion Syndrome Probe Combinations
  • Kallmann (KAL1) and Steroid Sulphatase Deficiency (STS) Probe Combination
  • Langer-Giedion
  • Monosomy 1p36
  • Neurofibromatosis Type 1
  • Prader-Willi/Angelman (SNRPN)
  • Rubinstein-Taybi
  • Saethre-Chotzen/Williams-Beuren Combination
  • SHOX
  • Smith-Magenis (RAI1 and FLII)/Miller-Dieker Probe Combinations
  • SRY
  • Williams-Beuren
  • Wolf Hirschhorn
  • XIST

For more information on the full list of Cytocell products visit our Cytocell FISH probes website

CytoSure™, SureSeq™ and myProbes®For research use only. Not for use in diagnostic procedures. Cytocell®: Some products may not be available in the US.

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