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The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings., (Copyright © 2018 American Society of Human Genetics. All rights reserved.)

Background: Recent changes to regulatory guidance in the US and Europe have complicated oversight of secondary research by rendering most uses of de-identified data exempt from human subjects oversight. To identify the implications of such guidelines for harms to participants and communities, this paper explores the secondary uses of one de-identified DNA sample collection with limited oversight: the Human Genome Diversity Project (HGDP)-Centre d'Etude du Polymorphisme Humain, Fondation Jean Dausset (CEPH) Human Genome Diversity Panel., Methods: Using a combination of keyword and cited reference search, we identified English-language scientific articles published between 2002 and 2009 that reported analysis of HGDP Diversity Panel samples and/or data. We then reviewed each article to identify the specific research use to which the samples and/or data was applied. Secondary uses were categorized according to the type and kind of research supported by the collection., Results: A wide variety of secondary uses were identified from 148 peer-reviewed articles. While the vast majority of these uses were consistent with the original intent of the collection, a minority of published reports described research whose primary findings could be regarded as controversial, objectionable, or potentially stigmatizing in their interpretation., Conclusions: We conclude that potential risks to participants and communities cannot be wholly eliminated by anonymization of individual data and suggest that explicit review of proposed secondary uses, by a Data Access Committee or similar internal oversight body with suitable stakeholder representation, should be a required component of the trustworthy governance of any repository of data or specimens.

A 3-kb region encompassing the beta-globin gene has been analyzed for allelic sequence polymorphism in nine populations from Africa, Asia, and Europe. A unique gene tree was constructed from 326 sequences of 349 in the total sample. New maximum-likelihood methods for analyzing gene trees on the basis of coalescence theory have been used. The most recent common ancestor of the beta-globin gene tree is a sequence found only in Africa and estimated to have arisen approximately 800,000 years ago. There is no evidence for an exponential expansion out of a bottlenecked founding population, and an effective population size of approximately 10,000 has been maintained. Modest differences in levels of beta-globin diversity between Africa and Asia are better explained by greater African effective population size than by greater time depth. There may have been a reduction of Asian effective population size in recent evolutionary history. Characteristically Asian ancestry is estimated to be older than 200,000 years, suggesting that the ancestral hominid population at this time was widely dispersed across Africa and Asia. Patterns of beta-globin diversity suggest extensive worldwide late Pleistocene gene flow and are not easily reconciled with a unidirectional migration out of Africa 100,000 years ago and total replacement of archaic populations in Asia.