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Objectives Assessing public attitudes about genomic medicine is critical for anticipating patient receptivity to clinical applications of genomics. Although scholars have highlighted the importance of assessing stakeholder opinions and views regarding advances in clinical genomics, to date there has not been a robust tool for measuring these attitudes. We designed a study to evaluate the validity of an instrument we developed for measuring attitudes about genomic medicine. Methods We used psychometric methods to validate the Genomic Orientation Scale (GO Scale). Our goal was to create an easy-to-use tool for evaluating positive and negative attitudes about genomic medicine. Results We describe the validation testing of the GO Scale in a nationally representative sample of 1536 individuals residing in the United States. We report results from convergent and divergent validity testing and Rasch modeling analysis. The study produced a 26-item scale with 2 dimensions—optimism and pessimism. Conclusions The GO Scale may be used to characterize attitudinal perspectives among patients, clinicians, and the public. The GO Scale may also be useful in evaluating shifts in attitude over time, for example, following educational interventions, which has not been feasible to date.

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.

Circular RNAs (circRNAs) from back-spliced exon(s) are characterized by the covalently closed loop feature with neither 5′ to 3′ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of circRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors. In this mini-review, we discuss our current understanding of circRNA biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circRNA formation. Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon(s). RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circRNAs generated in a single gene locus.

The ability to rapidly survey and compare gene expression levels between reference and test samples is moving the drug discovery process towards a more genomic orientation. The success of the Human Genome Project and related private genomics initiatives, combined with new technologies to probe, image and access expression data, are responsible for this transformation. This article reviews the history, status and future direction of high-throughput gene expression analysis. It describes classical approaches, explains the development of methods such as differential display for discovering novel genes, and discusses how microarray technology is exploiting collections of known sequences to pinpoint drug targets.

Background The human chromosome 8p23.1 region contains a 3.8–4.5 Mb segment which can be found in different orientations (defined as genomic inversion) among individuals. The identification of single nucleotide polymorphisms (SNPs) tightly linked to the genomic orientation of a given region should be useful to indirectly evaluate the genotypes of large genomic orientations in the individuals. Results We have identified 16 SNPs, which are in linkage disequilibrium (LD) with the 8p23.1 inversion as detected by fluorescent in situ hybridization (FISH). The variability of the 8p23.1 orientation in 150 HapMap samples was predicted using this set of SNPs and was verified by FISH in a subset of samples. Four genes (NEIL2, MSRA, CTSB and BLK) were found differentially expressed (p

In this chapter we will describe what is known about the regulation of the carbonic anhydrase (CA) genes closely clustered on human chromosome 8 and mouse chromosome 3, CA1, CA2 and CA3.(Fig. 1). These genes encode the cytosolic proteins CAI, CAII and CAIII which show considerable homology in their primary structures but differences in the detail of their catalytic properties. For example CAII has a CO2 turnover number at least 100 fold greater than that of CAIII, while CAIII has been shown to possess a unique phosphatase activity and can efficiently dephosphorylate phosphotyrosine residues (Cabiscol and Levine, 1996). These three genes are also distinguished by their temporal and spatial patterns of expression and this is likely to have arisen by sequence divergence in their regulatory elements after gene duplication. The promoters of the CA2 and CA3 genes are both G + C rich and show some localized sequence homologies which signal a common ancestry for their promoters, however the CAI promoter is not G + C rich and shows no homology to those of CA2 and A3. The CA1 gene is inverted in its genomic orientation relative to the other two genes. An inversion event sometime in the genomic history of this gene cluster could have led to the aquisition of novel 5’ flanking sequence and discrete regulatory control. Open image in new window Fig. 1 Map of the carbonic anhydrase gene cluster (CA1, CA2, and CA3) on human chromosome 8 (8q22). Exons are indicated as blocks; transcription start sites determined by two promoters in CA1 and CA2, and one in CA3 are shown as arrows. The major sites of expression for each gene promoter are indicated below.

The genome of Mycobacterium tuberculosis was analyzed using recently developed computational approaches to infer protein function and protein linkages. We evaluated and employed a method to infer genes likely to belong to the same operon, as judged by the nucleotide distance between genes in the same genomic orientation, and combined this method with those of the Rosetta Stone, Phylogenetic Profile and conserved Gene Neighbor computational methods for the inference of protein function.