Clinical OMICs - Issue 7 - (Page 5)

Clinical OMICs NEWS DO Manage Patient Expectations Counseling patients and their families about what to expect is essential, but challenging because they may be disappointed if extensive and expensive tests yield results that are inconclusive or indicated that no treatment is available. Most of the time, identifying a genetic cause won't lead to a cure. But even in these cases, exome sequencing may still be useful because it can end an expensive and potentially invasive and stressful diagnostic odyssey. DON'T Ignore the Limitations of the Sequencing Technologies Whole-genome sequencing. Whole-exome sequencing. They sound comprehensive, don't they? But so-called wholegenome sequencing doesn't cover 100% of the genome, any more than whole-exome sequencing covers 100% of the exome. Because of the way the target DNA sequences are gathered and assembled, not all of the DNA can be sequenced. Sequencing may not pick up longer variations or repetitions of sequences, or long deletions that are responsible for some genetic disorders. Rather, it is best at detecting single-nucleotide variants, or alterations in sequences www.clinicalomics.com of no more than 8-10 base pairs. Exome sequencing may not provide a diagnosis. On average, about 25% of such tests identify a gene variant that causes disease; most tests come up empty. Because of the technology's gaps, however, a negative result doesn't necessarily rule out a genetic cause for the disease. DON'T Overlook Incidental Findings Analysis of the results may produce incidental findings-discovery of a gene variant that is unrelated to the patient's primary disorder but that could cause disease and require medical surveillance or treatment for a separate condition. DO Explore Family Histories and Conduct Literature Searches A little homework can reveal which patients are most likely to benefit from clinical sequencing. For example, patients for whom the technology is most promising are those with rare disorders that seem to be the result of variants in a single gene. Physicians should explore family history-the presence and pattern of similar disorders among relatives. In addition, physicians should carry out an extensive literature search before ordering exome sequencing. Informed consent is essential. Image: Jane Ades, NHGRI The items in this list reflect the authors' decision to confine their overview to the analysis of germline sequence variants for diagnostic purposes. This decision reflects how most sequencing tests still serve to establish "diagnoses for rare, clinically unrecognizable, or puzzling disorders that are suspected to be genetic in origin." The authors acknowledged that sequencing has been hailed as an (continued on p. 21) July 16, 2014 Clinical OMICs 5 http://www.clinicalomics.com

Table of Contents for the Digital Edition of Clinical OMICs - Issue 7

Contents

Clinical OMICs - Issue 7