Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115941/1/jlme12295.pd

A standardized necropsy protocol for health investigations of small cetaceansin southern Africa

Globally, the increasing need to conduct both research and surveillance of the health of wild animal populations has been recognized as an important tool in conservation and management. While such studies on terrestrial wildlife are frequent in the southern African sub-region, their counterparts in the marine environment seem to be largely lacking. Here we report on our experience in establishing and testing a standardized necropsy protocol for small cetaceans adapted for the local context, with the specific aim of sampling for health investigations and monitoring. The necessity, challenge and value of regional standardization in data collection specifically aimed at health investigations, inter-disciplinary collaboration, long-term data banking,and sample storage are discussed in addition to practical and safety considerations. The developed protocol, focusing on the necropsy technique and tissue sample collection, as well as a list of required equipment are available as online supplementary material.The National Research Foundation (DFG-NRF collaboration programme grant number 70714 and SEAChange grant number 74241, both awarded to S. Plön).http://www.sawma.co.zaam201

Gene-specific ACMG/AMP classification criteria for germline APC variants: recommendations from the ClinGen InSIGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel

Purpose The Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) was established by the International Society for Gastrointestinal Hereditary Tumours and the Clinical Genome Resource, who set out to develop recommendations for the interpretation of germline APC variants underlying Familial Adenomatous Polyposis, the most frequent hereditary polyposis syndrome. Methods Through a rigorous process of database analysis, literature review, and expert elicitation, the APC VCEP derived gene-specific modifications to the ACMG/AMP (American College of Medical Genetics and Genomics and Association for Molecular Pathology) variant classification guidelines and validated such criteria through the pilot classification of 58 variants. Results The APC-specific criteria represented gene- and disease-informed specifications, including a quantitative approach to allele frequency thresholds, a stepwise decision tool for truncating variants, and semiquantitative evaluations of experimental and clinical data. Using the APC-specific criteria, 47% (27/58) of pilot variants were reclassified including 14 previous variants of uncertain significance (VUS). Conclusion The APC-specific ACMG/AMP criteria preserved the classification of well-characterized variants on ClinVar while substantially reducing the number of VUS by 56% (14/25). Moving forward, the APC VCEP will continue to interpret prioritized lists of VUS, the results of which will represent the most authoritative variant classification for widespread clinical use

Indian Ocean humpback dolphin (Sousa plumbea) movement patterns along the South African coast

1. The Indian Ocean humpback dolphin was recently uplisted to ‘Endangered’ in the recent South African National Red List assessment. Abundance estimates are available from a number of localized study sites, but knowledge of movement patterns and population linkage between these sites is poor. A national research collaboration, the SouSA project, was established in 2016 to address this key knowledge gap. Twenty identification catalogues collected between 2000 and 2016 in 13 different locations were collated and compared. 2. Photographs of 526 humpback dolphins (all catalogues and photos) were reduced to 337 individuals from 12 locations after data selection. Of these, 90 matches were found for 61 individuals over multiple sites, resulting in 247 uniquely, well‐marked humpback dolphins identified in South Africa. 3. Movements were observed along most of the coastline studied. Ranging distances had a median value of 120 km and varied from 30 km up to 500 km. Long‐term site fidelity was also evident in the data. Dolphins ranging along the south coast of South Africa seem to form one single population at the western end of the species' global range. 4. Current available photo‐identification data suggested national abundance may be well below previous estimates of 1000 individuals, with numbers possibly closer to 500. Bearing in mind the poor conservation status of the species in the country, the development of a national Biodiversity Management Plan aimed at ensuring the long‐term survival of the species in South Africa is strongly recommended. At the same time, increased research efforts are essential, particularly to allow for an in‐depth assessment of population numbers and drivers of changes therein. 5. The present study clearly indicates the importance of scientific collaboration when investigating highly mobile and endangered species.This collaborative research project was funded by the South African Network for Coastal and Oceanic Research (SANCOR), the National Research Foundation (NRF), and the University of Pretoria.http://wileyonlinelibrary.com/journal/aqc2019-02-01hj2018Mammal Research Institut

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Sound Generating Structures of the Humpback Dolphin Sousa plumbea (Cuvier, 1829) and the Directionality in Dolphin Sounds

The macroscopic morphology of structures involved in sound generation in the Indian Ocean humpback dolphin (Sousa plumbea) were described for the first time using computed tomography imaging and standard gross dissection techniques. The Indian Ocean humpback dolphin may represent a useful comparative model to the bottlenose dolphin (Tursiops sp.) to provide insights into the functional anatomy of the sound production in dolphins, since these coastal dolphins exhibit similar body size and share similarities on acoustic behavior. The general arrangement of sound generating structures, that is, air sacs and muscles, was similar in both the bottlenose dolphin and the Indian Ocean humpback dolphin. The main difference between the two species existed in a small left posterior branch of the melon in the Indian Ocean humpback dolphin, which was not found in the bottlenose dolphin and might reflect an adaptation of directionality for high frequency communication sounds as seen in some other delphinids (e.g., Lagenorhynchus sp., Grampus griseus). Thus, this may be the main reason for the asymmetry of the sound production structures in dolphins. Additionally, the longer rostrum in Indian Ocean humpback dolphins might suggest a more directional echolocation beam compared to the Lahille's bottlenose dolphin. Anat Rec, 302:849-860, 2019. (c) 2018 Wiley Periodicals, Inc

Science alone won’t do it! South Africa’s endangered humpback dolphins Sousa plumbea face complex conservation challenges

The Indian Ocean humpback dolphin (Sousa plumbea) is “endangered” with likely less than 500 animals remaining in South African waters. Established in 2016, the SouSA Consortium is a formalised network of scientists and conservationists to combine knowledge and research efforts, and make coordinated decisions with the aim of conserving the species. The first collaborative project collated available photoidentification data in an attempt to refine a national population estimate and investigate movements between research sites. This work was able to identify 250 uniquely marked individuals, with the population divided into the south-coast (Agulhas bioregion) and east-coast (Natal bioregion) populations. Environmental factors almost certainly play a role in the declining numbers of the species in South African waters. However, individual threats and solutions are challenging to identify as the South African marine environment is undergoing significant natural and anthropogenic changes with major shifts in the distribution and numbers of some prey, competitor and predator species. Therefore, we believe that a continued investigation of potential contributing factors and their interaction will take too long, inevitably resulting in another case of documenting extinction. With this in mind, we present the results of a SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis in an effort to help us identify the next steps to take toward the conservation of humpback dolphins in South African waters. We unanimously conclude that no single cause for the rapid decline of humpback dolphins Frontiers in in South African waters can be identified, and that the cumulative effects of multiple stressors, which are difficult to pinpoint and mitigate, are impacting population numbers. While highlighting the need for continued research, we suggest a shift toward more action-focused conservation efforts, the first concrete steps being the development of a Conservation Management Plan with input from other stakeholders.Gesellschaft zur Rettung der Delphine, the Western Indian Ocean Marine Science Association (WIOMSA), a University of Stellenbosch Sub Committee B Postdoctoral Fellowship and the Marine and Coastal grant of the National Research Foundation (NRF).https://www.frontiersin.org/journals/marine-science#am2022Mammal Research Institut