Preti Jain

The impact of returning secondary results from exome sequencing (ES) on patients/participants is important to understand as ES is increasingly utilized in clinical care and research. Participants were recruited from studies using ES and were separated into two arms: 107 who had ES and were offered the choice to learn secondary results (ES group) and 85 who had not yet had ES (No ES group). Questionnaires were administered at baseline and 1 and 12 months, following results disclosure (ES group) or enrollment (No ES group). While the majority (65%) elected to learn all results following pre-test counseling, it was reduced from the 76% who indicated a desire for all results at baseline. Thirty-seven percent received results associated with an increased personal disease risk. There were no differences in changes in any of the psychological and social measures from baseline to post-results disclosure between the ES and No ES groups. Receiving a wide range of secondary findings appeared to have little measurable impact on most participants. The experience of learning secondary results may be related to participants' previous experiences with genetics, as well as the genetic counseling provided. Future research with a more diverse, genetically naïve group, as well as scalable methods of delivery, is needed.

BACKGROUND: Genome-wide maps of transcription factor binding sites in primary tissues can expand our understanding of genome function, transcriptional regulation, and genetic alterations that contribute to disease risk. However, almost all genome-wide studies of transcription factors have been in cell lines, and performing these experiments in tissues has been technically challenging and limited in throughput. RESULTS: Here we outline a simple strategy for mapping transcription factor binding sites in frozen tissues that utilizes dry pulverization of samples and is scalable for high-throughput analyses. We show that the method leads to accurate and reproducible chromatin immunoprecipitation next-generation sequencing (ChIP-seq) data, and is highly sensitive, identifying high-quality transcription factor binding sites from chromatin corresponding to only 5 mg of liver tissue. CONCLUSIONS: The enhanced reproducibility, robustness, and sensitivity of the dry pulverization method, in addition to the ease of implementation and scalability, makes ChIP-seq in primary tissues a widely accessible assay.