When we study rare and inherited diseases, we find a wide spectrum of genetic and phenotypic heterogeneity and an equally wide selection of causative mutation types. No single platform is capable of finding all causative variants with the speed and cost efficiency needed in a typical research setting.
Here are examples of human genetic disease projects and technology solutions that can deliver meaningful data within a week from sample to data.
Whether you need to analyse one gene or thousands of genes, we enable you to select the right tool for the job, helping you to find answers more efficiently.
Educational content
See how you can quickly identify causative alleles in inherited diseases through candidate gene analysis using next generation sequencing of custom-assembled gene panels.
| For multiplex analysis of multiple genes, multiple samples for low cost variant detection: | |||
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| For single gene, single sample variant detection or NGS verification: | |||
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Inherited diseases can also be caused by a combination of genetic loci which together result in potentially complex and variable phenotype, making disease identification more difficult. We show how a combination of chromosomal microarray analysis (CMA) and whole exome analysis (WES) can improve discovery rates over WES alone.
Recent studies have shown that a combination of genomic array and sequential exome analysis, is an effective approach in the evaluation of subjects with unexplained intellectual disability, autism spectrum disorder and/or congenital anomalies. The expected clinical yield of these tests are for high resolution genomic array 15-20% and in combination with exome sequencing >50% (Vissers L et al. Nature Genetics, 2010, PMID: 21076407).
Molecular diagnostic yield of chromosomal microarray analysis and whole exome analysis using next-generation sequencing in children with autism spectrum disorder. Tammimies K et al. (2015) JAMA
Non-familial congenital & germline disorders Reproductive health research Complex traits & pharmacogenomics
Incurable neurodegenerative diseases such as Huntington’s disease, spinocerebellar ataxias, fragile X syndrome, and SBMA are caused by unstable repetitive triplet elements within defined loci. Variability in repeat length is observed in normal alleles and can range from 15 to 40 nucleotides. Pathology results when repeat length exceeds a specific threshold, usually greater than 45. The disease phenotype may worsen from generation to generation due to de novo germline expansion of repeats.
More than 30 Mendelian disorders are linked to STR expansions. In Fragile X syndrome, tandem CGG repeats within the FMR1 gene are associated with onset and severity of frontotemporal dementia and amyotrophic lateral sclerosis.
A rare genetic disorder of ciliary function, affecting 1/20,000 live births, this disease has phenotypic heterogeneity and is difficult to diagnose. Early diagnosis is essential for effective disease management. Kano G et al. (2016) Mol Med Reports
Identified two DNAH5 (dynein heavy chain 5) mutations:
Human genetics research studies provide the disease-predisposing alleles that then feed into family planning screening tools. If two parents are both carriers of a recessive, disease-linked gene, then there is a 25% chance that their children will inherit the disease in question. Understanding the risk factors in different populations is the first stage in developing preventative medicine.
Carrier screening determines whether a healthy person possesses a copy of a disease-linked gene. The ideal carrier screening tool needs to incorporate all possible deleterious mutations that are found across ethnicities so that just a single test can be applied in every subject studied. This approach would cut down work, costs and multiple rounds of trial and error.
Overcome the challenges of the exome odyssey with reliable single-exon deletion and duplication detection using the Applied Biosystems CytoScan XON Suite, for cost-effective and streamlined analysis of exon-level CNVs. Designed to cover the whole genome, with increased coverage in 7,000 clinically relevant genes, the CytoScan XON Suite provides CNV data that works as a strong complement to mutation analysis performed by next-generation sequencing (NGS).
Genotyping continues to be an important molecular tool for precision medicine in the research and clinical setting. Study strategy has evolved rapidly in recent years, led by large population biobanks and precision medicine initiatives. Below, you can access the experience of leaders in the field on how they have solved the common genotyping challenges in complex trait genomics and pharmacogenomics.
Learn how UK Biobank solved this challenge by reading this interview with Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford and Consultant Endocrinologist at the Oxford University Hospitals Trust, Oxford, UK.
In this webinar, Dr. Mark Bouzyk, Cofounder and Chief Scientific Officer of AKESOgen, USA, talks about his experience working on pharmacogenomics studies and the Million Veterans Program.
In this interview, Ulrich Broeckel, MD from Right Patient, Right Drug Diagnostics, USA discusses the value of and research into pre-emptive pharmacogenomics.
See how you can quickly identify causative alleles in inherited diseases through candidate gene analysis using next generation sequencing of custom-assembled gene panels.
| For multiplex analysis of multiple genes, multiple samples for low cost variant detection: | |||
| | ||
| |||
| For single gene, single sample variant detection or NGS verification: | |||
| | ||
Inherited diseases can also be caused by a combination of genetic loci which together result in potentially complex and variable phenotype, making disease identification more difficult. We show how a combination of chromosomal microarray analysis (CMA) and whole exome analysis (WES) can improve discovery rates over WES alone.
Recent studies have shown that a combination of genomic array and sequential exome analysis, is an effective approach in the evaluation of subjects with unexplained intellectual disability, autism spectrum disorder and/or congenital anomalies. The expected clinical yield of these tests are for high resolution genomic array 15-20% and in combination with exome sequencing >50% (Vissers L et al. Nature Genetics, 2010, PMID: 21076407).
Molecular diagnostic yield of chromosomal microarray analysis and whole exome analysis using next-generation sequencing in children with autism spectrum disorder. Tammimies K et al. (2015) JAMA
Non-familial congenital & germline disorders Reproductive health research Complex traits & pharmacogenomics
Incurable neurodegenerative diseases such as Huntington’s disease, spinocerebellar ataxias, fragile X syndrome, and SBMA are caused by unstable repetitive triplet elements within defined loci. Variability in repeat length is observed in normal alleles and can range from 15 to 40 nucleotides. Pathology results when repeat length exceeds a specific threshold, usually greater than 45. The disease phenotype may worsen from generation to generation due to de novo germline expansion of repeats.
More than 30 Mendelian disorders are linked to STR expansions. In Fragile X syndrome, tandem CGG repeats within the FMR1 gene are associated with onset and severity of frontotemporal dementia and amyotrophic lateral sclerosis.
A rare genetic disorder of ciliary function, affecting 1/20,000 live births, this disease has phenotypic heterogeneity and is difficult to diagnose. Early diagnosis is essential for effective disease management. Kano G et al. (2016) Mol Med Reports
Identified two DNAH5 (dynein heavy chain 5) mutations:
Human genetics research studies provide the disease-predisposing alleles that then feed into family planning screening tools. If two parents are both carriers of a recessive, disease-linked gene, then there is a 25% chance that their children will inherit the disease in question. Understanding the risk factors in different populations is the first stage in developing preventative medicine.
Carrier screening determines whether a healthy person possesses a copy of a disease-linked gene. The ideal carrier screening tool needs to incorporate all possible deleterious mutations that are found across ethnicities so that just a single test can be applied in every subject studied. This approach would cut down work, costs and multiple rounds of trial and error.
Overcome the challenges of the exome odyssey with reliable single-exon deletion and duplication detection using the Applied Biosystems CytoScan XON Suite, for cost-effective and streamlined analysis of exon-level CNVs. Designed to cover the whole genome, with increased coverage in 7,000 clinically relevant genes, the CytoScan XON Suite provides CNV data that works as a strong complement to mutation analysis performed by next-generation sequencing (NGS).
Genotyping continues to be an important molecular tool for precision medicine in the research and clinical setting. Study strategy has evolved rapidly in recent years, led by large population biobanks and precision medicine initiatives. Below, you can access the experience of leaders in the field on how they have solved the common genotyping challenges in complex trait genomics and pharmacogenomics.
Learn how UK Biobank solved this challenge by reading this interview with Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford and Consultant Endocrinologist at the Oxford University Hospitals Trust, Oxford, UK.
In this webinar, Dr. Mark Bouzyk, Cofounder and Chief Scientific Officer of AKESOgen, USA, talks about his experience working on pharmacogenomics studies and the Million Veterans Program.
In this interview, Ulrich Broeckel, MD from Right Patient, Right Drug Diagnostics, USA discusses the value of and research into pre-emptive pharmacogenomics.
For Research Use Only. Not for use in diagnostic procedures.
