Another Week | Another Tool - A Digital Humanities Barnraising

The Roy Rosenzweig Center for History and New Media (CHNM) at George Mason University proposes a reprise of One Week | One Tool for summer 2013. Another Week | Another Tool: A Digital Humanities Barnraising will once again bring together a group of twelve digital scholars, students, librarians, and museum professionals of diverse disciplinary backgrounds and practical experience to CHNM to build something useful and useable in seven days. Not for the faint of heart, a one-day course of training in the principles of open source software development will be followed by an intense six days of doing and a year of continued community engagement, development, testing, dissemination, and evaluation. Comprised of designers and programmers as well as project managers and outreach specialists, the group will conceive a tool, outline a roadmap, develop and disseminate a modest prototype, lay the ground work for building an open source community, and make first steps toward securing the project's long-term sustainability

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Counselees’ Perspectives of Genomic Counseling Following Online Receipt of Multiple Actionable Complex Disease and Pharmacogenomic Results: a Qualitative Research Study

Genomic applications raise multiple challenges including the optimization of genomic counseling (GC) services as part of the results delivery process. More information on patients’ motivations, preferences, and informational needs are essential to guide the development of new, more efficient practice delivery models that capitalize on the existing strengths of a limited genetic counseling workforce. Semi‐structured telephone interviews were conducted with a subset of counselees from the Coriell Personalized Medicine Collaborative following online receipt of multiple personalized genomic test reports. Participants previously had either in‐person GC (chronic disease cohort, n = 20; mean age 60 years) or telephone GC (community cohort, n = 31; mean age 46.8 years). Transcripts were analyzed using a Grounded Theory framework. Major themes that emerged from the interviews include 1) primary reasons for seeking GC were to clarify results, put results into perspective relative to other health‐related concerns, and to receive personalized recommendations; 2) there is need for a more participant driven approach in terms of mode of GC communication (in‐person, phone, video), and refining the counseling agenda pre‐session; and 3) there was strong interest in the option of follow up GC. By clarifying counselees’ expectations, views and desired outcomes, we have uncovered a need for a more participant‐driven GC model when potentially actionable genomic results are received online.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146805/1/jgc40738.pd

Operationalizing the Reciprocal Engagement Model of Genetic Counseling Practice: a Framework for the Scalable Delivery of Genomic Counseling and Testing

With the advent of widespread genomic testing for diagnostic indications and disease risk assessment, there is increased need to optimize genetic counseling services to support the scalable delivery of precision medicine. Here, we describe how we operationalized the reciprocal engagement model of genetic counseling practice to develop a framework of counseling components and strategies for the delivery of genomic results. This framework was constructed based upon qualitative research with patients receiving genomic counseling following online receipt of potentially actionable complex disease and pharmacogenomics reports. Consultation with a transdisciplinary group of investigators, including practicing genetic counselors, was sought to ensure broad scope and applicability of these strategies for use with any large‐scale genomic testing effort. We preserve the provision of pre‐test education and informed consent as established in Mendelian/single‐gene disease genetic counseling practice. Following receipt of genomic results, patients are afforded the opportunity to tailor the counseling agenda by selecting the specific test results they wish to discuss, specifying questions for discussion, and indicating their preference for counseling modality. The genetic counselor uses these patient preferences to set the genomic counseling session and to personalize result communication and risk reduction recommendations. Tailored visual aids and result summary reports divide areas of risk (genetic variant, family history, lifestyle) for each disease to facilitate discussion of multiple disease risks. Post‐counseling, session summary reports are actively routed to both the patient and their physician team to encourage review and follow‐up. Given the breadth of genomic information potentially resulting from genomic testing, this framework is put forth as a starting point to meet the need for scalable genetic counseling services in the delivery of precision medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/1/jgc41111.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147027/2/jgc41111-sup-0001.pd

Mendelian breeding units versus standard sampling strategies: Mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling

Outcomes of a Randomized Controlled Trial of Genomic Counseling for Patients Receiving Personalized and Actionable Complex Disease Reports

There has been very limited study of patients with chronic disease receiving potentially actionable genomic based results or the utilization of genetic counselors in the online result delivery process. We conducted a randomized controlled trial on 199 patients with chronic disease each receiving eight personalized and actionable complex disease reports online. Primary study aims were to assess the impact of in‐person genomic counseling on 1) causal attribution of disease risk, 2) personal awareness of disease risk, and 3) perceived risk of developing a particular disease. Of 98 intervention arm participants (mean age = 57.8; 39% female) randomized for in‐person genomic counseling, 76 (78%) were seen. In contrast, control arm participants (n = 101; mean age = 58.5; 54% female) were initially not offered genomic counseling as part of the study protocol but were able to access in‐person genomic counseling, if they requested it, 3‐months post viewing of at least one test report and post‐completion of the study‐specific follow‐up survey. A total of 64 intervention arm and 59 control arm participants completed follow‐up survey measures. We found that participants receiving in‐person genomic counseling had enhanced objective understanding of the genetic variant risk contribution for multiple complex diseases. Genomic counseling was associated with lowered participant causal beliefs in genetic influence across all eight diseases, compared to control participants. Our findings also illustrate that for the majority of diseases under study, intervention arm participants believed they knew their genetic risk status better than control arm subjects. Disease risk was modified for the majority during genomic counseling, due to the assessment of more comprehensive family history. In conclusion, for patients receiving personalized and actionable genomic results through a web portal, genomic counseling enhanced their objective understanding of the genetic variant risk contribution to multiple common diseases. These results support the development of additional genomic counseling interventions to ensure a high level of patient comprehension and improve patient‐centered health outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147048/1/jgc40980.pd