Purpose Examination of patients’ responses to direct-to-consumer genetic susceptibility tests is needed to inform clinical practice. This study examined patients’ recall and interpretation of, and responses to, genetic susceptibility test results provided directly by mail. Methods This observational study had 3 prospective assessments (before testing; 10 days after receiving results; 3 months later). Participants were 199 patients aged 25–40 who received free genetic susceptibility testing for 8 common health conditions. Results Over 80% correctly recalled their results for the 8 health conditions. Patients were unlikely to interpret genetic results as deterministic of health outcomes (mean=6.0, SD=0.8 on 1–7 scale, 1 indicating strongly deterministic). In multivariate analyses, patients with the least deterministic interpretations were White (p=.0098), more educated (p=.0093), and least confused by results (p=.001). Only 1% talked about their results with a provider. Conclusion Findings suggest that most patients will correctly recall their results and will not interpret genetics as the sole cause of diseases. The subset of those confused by results could benefit from consultation with a health care provider, which could emphasize that health habits currently are the best predictors of risk. Providers could leverage patients’ interest in genetic tests to encourage behavior changes to reduce disease risk.

The ribosome biogenesis pathway constitutes one of the major metabolic obligations for a dividing yeast cell and it depends upon the activity of hundreds of gene products to produce the necessary rRNA and ribosomal protein components. Previously, we reported that a set of 65 S. cerevisiae genes that function in the rRNA biosynthesis pathway are transcriptionally co-regulated as cells pass through a variety of physiological transitions. By analysing multiple microarray-based transcriptional datasets, we have extended that study and now suggest that the ribosomal and rRNA biosynthesis regulon contains over 200 genes. This regulon is distinct from the set of ribosomal protein genes, and the promoters of the expanded RRB gene set are highly enriched for the PAC and RRPE motifs. Since a similar pattern of organization and gene regulation can be recognized in C. albicans, the RRB regulon appears to be a conserved, extensive, and metabolically important group of genes.

In an effort to identify sets of yeast genes that are coregulated across various cellular transitions, gene expression data sets derived from yeast cells progressing through the cell cycle, sporulation, and diauxic shift were analyzed. A partitioning algorithm was used to divide each data set into 24 clusters of similar expression profiles, and the membership of the clusters was compared across the three experiments. A single cluster of 189 genes from the cell cycle experiment was found to share 65 genes with a cluster of 159 genes from the sporulation data set. Many of these genes were found to be clustered in the diauxic-shift experiment as well. The overlapping set was enriched for genes required for rRNA biosynthesis and included genes encoding RNA helicases, subunits of RNA polymerases I and III, and rRNA processing factors. A subset of the 65 genes was tested for expression by a quantitative-relative reverse transcriptase PCR technique, and they were found to be coregulated after release from alpha factor arrest, heat shock, and tunicamycin treatment. Promoter scanning analysis revealed that the 65 genes within this ribosome and rRNA biosynthesis (RRB) regulon were enriched for two motifs: the 13-base GCGATGAGATGAG and the 11-base TGAAAAATTTT consensus sequences. Both motifs were found to be important for promoting gene expression after release from alpha factor arrest in a test rRNA processing gene (EBP2), which suggests that these consensus sequences may function broadly in the regulation of a set of genes required for ribosome and rRNA biosynthesis.Ribosome biosynthesis is a complex and demanding process that depends directly upon multiple metabolic pathways, including the activities of three different RNA polymerases (reviewed in references 21 and 27). In Saccharomyces cerevisiae there are 137 ribosomal protein genes (RP genes), and they are transcribed by RNA polymerase II to yield 78 ribosomal proteins. Because the RP genes are transcribed at such a high level, together they account for nearly 50% of the total RNA polymerase II-mediated transcription initiation events (18). The 25S, 18S, and 5.8S rRNAs are synthesized by RNA polymerase I, first as a large 35S transcript that subsequently gets processed into the three smaller, mature species. Synthesis of the 5S rRNA is distinct from the other rRNAs and is carried out by RNA polymerase III. In order to achieve the high levels of rRNA production that are required during rapid cell division, yeast cells contain roughly 150 repeats of the rRNA genes in a tandem array on chromosome XII. Together, these repeats represent 10% of the genome, and rRNA production alone accounts for some 60% of the total cellular transcription.Ribosome biogenesis also depends upon the activities of a large number of protein and RNA molecules that are not themselves components of the final ribosome. The complex processing pathway that converts the 35S precursor rRNA into the mature 25S, 18S, and 5.8S rRNA species requires a multitude of factors, including RNA endonucleases, exon...

Purpose: As advances in research have made a growing number of genetic tests available, clinicians will increasingly be faced with making decisions about when offering genetic testing services to children is appropriate. A key factor in such decisions involves determining whether knowledge of genetic health risks might have an impact on children's psychosocial wellbeing. Methods: We conducted a systematic review of the literature using five online databases to identify studies that assessed the impact of communicating nondiagnostic carrier or presymptomatic genetic test results to children. Results: A total of 17 articles met the inclusion criteria for this review. These studies used a wide range of methodologies to explore carrier and predictive testing. Although there was little quantitative evidence that receiving genetic test results led to a significant impact on children's psychosocial wellbeing, it was found that methodological inconsistencies, small samples, and reliance on assessments most appropriate for psychopathology make any firm conclusions about the impact of genetic testing on children premature. Conclusion: Currently, there is insufficient evidence to inform a nuanced understanding of how children respond to genetic testing. This suggests a strong need for further research that uses rigorous approaches to address children's emotional states, self-perception, and social wellbeing. Genet Med 2010:12(6):317-326.