We established a general genetic counseling clinic (GCC) to help reduce long wait times for new patient appointments and to enhance services for a subset of patients. Genetic counselors, who are licensed in Tennessee, were the primary providers and MD geneticists served as medical advisors. This article describes the clinic referral sources, reasons for referral and patient dispositions following their GCC visit(s). We obtained patients by triaging referrals made to our medical genetics division. Over 24 months, our GCC provided timely visits for 321 patients, allowing the MD geneticists to focus on patients needing a clinical exam and/or complex medical management. Following their GCC visit(s), over 80 % of patients did not need additional appointments with an MD geneticist. The GCC allowed the genetic counselor to spend more time with patients than is possible in our traditional medical genetics clinic. Patient satisfaction surveys (n = 30) were very positive overall concerning the care provided. Added benefits for the genetic counselors were increased professional responsibility, autonomy and visibility as health care providers. We conclude that genetic counselors are accepted as health care providers by patients and referring providers for a subset of clinical genetics cases. A GCC can expand genetic services, complement more traditional genetic clinic models and utilize the strengths of the genetic counselor health care provider.

We sought evidence of publication bias to explain conflicting findings in studies of angiotensin-converting enzyme deletion polymorphism (ACE D) and glycoprotein IIIa PlA2 (PLA2) polymorphism and the risk of myocardial infarction. Factor 5 Leiden (F5L), a well-established thrombotic risk factor, served as an internal comparison. We conducted systematic reviews of published studies involving ACE D, PLA2, F5L and relevant outcomes, searching medline (January 1990 through February, 2001), bibliographies, and meta-analyses. Random effects pooled odds ratios (95% confidence interval) for cardiovascular outcomes were as follows: PLA2 (n = 13,167 subjects): 1.13 (1.02, 1.26); ACE D (n = 42,140 subjects): 1.22 (1.11, 1.35); and F5L (n = 27,277 subjects): 4.43 (3.65, 5.38). However, funnel plots of ACE D and PLA2, but not F5L, showed an inverse relationship between sample size and odds ratios for ACE D (p = 0.02) and PLA2 (p = 0.04) but not F5L (p = 0.65) by Egger's test for potential publication bias. Despite research-based genotyping of over 50,000 subjects, the overall risk for myocardial infarction as a result of PLA2 and ACE D remains doubtful. Our study provides a clear example of how publication of underpowered studies can spuriously implicate polymorphisms as genetic risk factors.

High throughput molecular and functional profiling of patients is a key driver of precision medicine. DNA and RNA characterization has been enabled at unprecedented cost and scale through rapid, disruptive progress in sequencing technology, but challenges persist in data management and interpretation. We analyze the state-of-the-art of large-scale unbiased sequencing in drug discovery and development, including technology, application, ethical, regulatory, policy and commercial considerations, and discuss issues of LUS implementation in clinical and regulatory practice.