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Genetic screening in patients of reproductive age. How do you advise prospective parents who want to know specific risks?

At times, determining the actual genetic condition occurring in a family can be very difficult. The most important steps in deciding when testing is appropriate are the patient's age and family history, with special attention to ethnic background. By identifying risk factors before pregnancy, prospective parents can be fully informed about their specific risk of having a child with a genetic condition. Furthermore, the pros and cons of invasive prenatal diagnostic procedures often can be fully discussed well in advance of an actual pregnancy. Clinical geneticists and genetic counselors can provide valuable assistance when difficult questions or problems arise.

Adult↗

A genetic screen targeting the tumor necrosis factor/Eiger signaling pathway: identification of Drosophila TAB2 as a functionally conserved component.

Signaling by tumor necrosis factors (TNFs) plays a prominent role in mammalian development and disease. To fully understand this complex signaling pathway it is important to identify all regulators and transduction components. A single TNF family member, Eiger, is encoded in the Drosophila genome, offering the possibility of applying genetic approaches for pursuing this goal. Here we present a screen for the isolation of novel genes involved in the TNF/Eiger pathway. On the basis of Eiger's ability to potently activate Jun-N-terminal kinase (JNK) and trigger apoptosis, we used the Drosophila eye to establish an assay for dominant suppressors of this activity. In a large-scale screen the Drosophila homolog of TAB2/3 (dTAB2) was identified as an essential component of the Eiger-JNK pathway. Genetic epistasis and biochemical protein-protein interaction assays assign an adaptor role to dTAB2, linking dTRAF1 to the JNKKK dTAK1, demonstrating a conserved mechanism of TNF signal transduction in mammals and Drosophila. Thus, in contrast to morphogenetic processes, such as dorsal closure of the embryo, in which the JNK pathway is activated by the JNKKK Slipper, Eiger uses the dTAB2-dTAK1 module to induce JNK signaling activity.

Adaptor Proteins, Signal Transducing↗

Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils.

This article examines evidence for the potential benefit of genetic testing for SSRI response, as well as potential ethical and practical implications of the implementation of this test into standard psychiatric practice. We reviewed three areas of the literature: the burden of treatment-resistant and treatment-intolerant major depressive disorders, the evidence for the value of genetic testing to predict drug response, and the ethical and practical issues of genetic testing in usual care. Treatment resistance and treatment intolerance are common for persons treated with selective serotonin reuptake inhibitors (SSRIs) and are associated with both financial and quality-of-life costs. There is strong evidence from association studies that some polymorphisms are associated with SSRI response. However, no randomized trials have yet tested the efficacy of genetic tests to improve outcome in those with treatment resistance or treatment intolerance to SSRIs. Given the nonspecific nature of the test proposed, several ethical concerns are also involved with administering the genetic tests to patients. A randomized trial comparing response in those treated with standard psychiatric care and in those treated with psychiatric care tailored as a result of genetic test results should be completed before the implementation of these tests can be considered. Additionally, the ethical and practical questions concerning the tests must be addressed now, so that the potential impact of these tests on patient care can be well understood prior to adoption in standard practice.

Antidepressive Agents, Second-Generation↗