Next-generation sequencing for rare genetic disorders

Next-generation sequencing for rare genetic disorders

Abstracts / Current Opinion in Biotechnology 22S (2011) S15–S152 generative disorders; blindness, deafness, cardiomyopathy; long QT syndrome; Noonan ...

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Abstracts / Current Opinion in Biotechnology 22S (2011) S15–S152

generative disorders; blindness, deafness, cardiomyopathy; long QT syndrome; Noonan and related conditions etc). This will largely replace the testing of single genes, or of several genes in succession as is now customary. The projected cost of consumables for sequencing all 21000 human genes (the exome) using the SOLID platform is 2000 Euros. This could be used to test for instance to detect de novo changes in mental retardation patients. Turnaround time will need to go down, but 3-4 weeks is probably not unrealistic in the mid-term. The impact of this will be manifold: • Diagnostic testing of genes will move to the front end of the diagnostic process in many clinical situations. When a patient is seen in the outpatient clinic, an exome may already be done by the time the patient is seen for the first visit. • This means that clinical geneticists should themselves aim to be involved in the diagnostic process from the start. This argues for multidisciplinary diagnostic clinics • Clinical diagnostic skills (in dysmorphology, or other) will become less important. Because the question which gene is to be tested is no longer paramount. • Understanding genes and their functions in terms of the human organism becomes a critical skill for clinical geneticists. • Numerous patients will be diagnosed with unique (new) genetic conditions. Note that this is already happening for copy number variation. This calls for geneticists to participate and perhaps organize specialist clinics for (very) rare diseases. Geneticists should develop skills that allow them to feel comfortable in their role as the ultimate expert on a subset of these very rare conditions. • Clinical geneticists should consider setting up services for the public that deal with incidental and minor findings on exome analysis. This may well be in the shape of e-consults rather than of formal outpatient clinics. • The counseling element of clinical genetics (What am I to do with my life, given my genetic profile and risks?) remains essentially unchanged.


CCL6 Predictive diagnostics and targeted preventive measures as the cost-effective platform for personalised medicine Vincenzo Costigliola European Association for Predictive, Preventive and Personalised Medicine, Brussels, Belgium E-mail address: [email protected] Optimistic versus Pessimistic Prognosis depends much on diagnostic, preventive and treatment approaches which healthcare will preferably adopt in the near future. Without innovation in healthcare, for example in years around 2030 the prevalence of Diabetes mellitus will reach the dimension of a half of billion of affected people worldwide additionally burdened with a spectrum of secondary complications (cancer, cardiovascular and neurodegenerative diseases) and concomitant enormous economical burden linked to the treatment. In the same period of time, neurodegenerative pathologies (Alzheimer’s and Parkinson’s diseases, glaucoma and macular degeneration, etc.) can reach more than 30% of global disease burden. In contrast, effective utilisation of advanced early/predictive diagnostics, preventive and personalised medical approaches could enable a significant portion of population to reach the 100-year age limit remaining vibrant in excellent physical and mental health as actively contributing members of society. Global research and implementation programmes in biomedicine, communication among scientific societies, healthcare-providers, policy-makers, educators and organised patient groups and, finely, a consolidation of professional groups in the branch of personalised medicine will play a decisive role in driving the situation in favour of one of two scenarios (Optimistic versus Pessimistic Prognosis) over the next 5–10 years. doi:10.1016/j.copbio.2011.05.023



Nanobiotechnology for neurodegenerative and proteinmisfolding diseases


Ratnesh Lal, Fernando Teran Arce, Srinivasan Ramachandran, Laura Connelly, Ricardo Capone

Next-generation sequencing for rare genetic disorders

University of California San Diego, La Jolla, CA, USA

Mustafa Tekin

E-mail address: [email protected] (R. Lal)

John T Macdonald Foundation, Department of Human Genetics and John P Hussman Institute for Human Genomics, University of Miami Miller, School of Medicine, Miami, FL, USA

Application of nanotechnology in biology and medicine is emerging as a powerful field, as it provides means to measure, monitor and manipulate fundamental biological processes of both normal and abnormal states at their native length-scales relevant to the normal physiology and pathological human diseases. In particular, it has provided an important set of visualization and hypothesis-testing tools to the family of neurodegenerative and protein-misfolding diseases, including Alzheimer’s, Huntington’s, Parkinson’s diseases and bovine spongiform encephalopathy among its insidious members. Nanotechnological tools for the visualization of living biological systems, such as Atomic Force Microscope has provided three dimensional molecular scale images polymorphic structures adopted by amyloid peptides, believed to be at the core of Alzheimer’s disease (AD). The amyloid peptides make toxic ion channels that underlie the early key events in the pathology of AD, as well as in other neurodegenerative and protein-misfolding diseases. Integrated AFMs with nanopore devices and electrical recording and imaging tools will give us combined functional and structural information about these toxic

E-mail address: [email protected] DNA sequencing is considered the gold standard for the detection of disease-causing single nucleotide changes and small insertion/deletions that are present in a given gene. The nextgeneration sequencing technology is highly promising for the description of DNA variations either in previously described disease-associated genes or in making new pathogenetic associations. Entire genome or a region of interest, for instance the whole exome, can be sequenced with this technology. Recent developments in DNA sequencing technology heralds the opening of a new era in finding molecular basis of genetic disorders and in general medical applications of the genetic knowledge. doi:10.1016/j.copbio.2011.05.022