A Self-Guided Tour of One’s Genome

see Self-guided management of exome and whole-genome sequencing results: changing the results return model

Debate within the clinical genetics community about how to return whole-genome and whole-exome data to individuals has tended to focus on genomic data as “results.” In this issue, a research team from the University of Washington proposes shifting the emphasis from returning results to providing a kind of atlas that can be accessed over time as health and life circumstances warrant. This genomic atlas would, in their view, allow a self-directed tour that could be as short or as long a journey as desired. Reframing the debate to focus on self-guided management rather than return of results would allow individuals to determine whether and when they receive results. It would also, the authors argue, “reduce the practical burden of forcing providers to act as gatekeepers of the broad scope of results with ever-changing implications for the health of their patients.” In such a system, the roles of genetic counselors and clinical geneticists would, over time, shift to providing an interpretive safety net for recipients. Return of results would no longer be a one-time interaction but an ongoing process. Genetic counseling would become a long-term relationship at a pace driven by recipients. The authors suggest that this platform would relieve some of the ethical burden currently felt by clinicians while also conforming to standards of bioethics. However, the question of who should bear the responsibility of maintaining sequence data remains. Within the proposed framework, the authors propose that researchers focus on “how, by what mechanisms, to what extent, in what contexts, and with what outcomes results will be offered and returned.” —Karyn Hede, News Editor

The Hereditary Ataxias: a Review

see page Hereditary ataxias: overview

The hereditary ataxias often present with an array of overlapping symptoms that require molecular genetic testing to discriminate between them. All individuals with ataxia have problems with gross motor coordination due to defects in the nervous system that affect movement and balance. In addition, they may develop problems with eye movement, spasticity, neuropathy, and cognitive/behavioral difficulties. Establishing the specific molecular cause of hereditary ataxia for any given individual generally requires obtaining medical and family history, physical and neurologic examinations, and neuroimaging, in addition to molecular genetic testing. In this issue, Jayadev and Bird present the current understanding of these diverse disorders, including both the autosomal dominant and recessive forms, and review accepted steps for differential diagnosis. The authors review evaluation strategies, including non-DNA and DNA testing methods, as well as available prenatal testing for some forms of the disorder. Progress in identifying causative genes has enabled diagnosis of an estimated 50–60% of the dominant hereditary ataxias via a battery of genetic tests. Many laboratories first test for the genes associated with the more common ataxias (SCA1, SCA2, SCA3, SCA6, and SCA7), offering a second tier of tests only if the first group yields no positive diagnosis. Challenges and approaches to genetic counseling and disease management are also briefly covered. —Karyn Hede, News Editor