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Rare copy-number variants (rCNVs) include deletions and duplications that occur infrequently in the global human population and can confer substantial risk for disease. In this study, we aimed to quantify the prop-erties of haploinsufficiency (i.e., deletion intolerance) and triplosensitivity (i.e., duplication intolerance) throughout the human genome. We harmonized and meta-analyzed rCNVs from nearly one million individuals to construct a genome-wide catalog of dosage sensitivity across 54 disorders, which defined 163 dosage sensitive segments associated with at least one disorder. These segments were typically gene dense and often harbored dominant dosage sensitive driver genes, which we were able to prioritize using statistical fine-mapping. Finally, we designed an ensemble machine-learning model to predict probabilities of dosage sensitivity (pHaplo & pTriplo) for all autosomal genes, which identified 2,987 haploinsufficient and 1,559 trip-losensitive genes, including 648 that were uniquely triplosensitive. This dosage sensitivity resource will pro-vide broad utility for human disease research and clinical genetics.

OBJECTIVES: The Tuskegee Syphilis Study and HIV conspiracy beliefs have continuing effects on perceptions of medical research in the African American community. This study was designed to explore how knowledge and beliefs concerning the Tuskegee Study and HIV impact African Americans' willingness to partake in medical research, how research incentives may influence that willingness and what level of importance they believe medical research has in their lives.METHODS: Responses to medical research questionnaires were assessed for 100 participants. Outcome measures included accuracy of Tuskegee study knowledge, likelihood of participation in research based on incentives, level of importance of research and enrollment into a recruitment database. Data concerning knowledge and beliefs of the Tuskegee Study and HIV, likelihood of participation and level of importance were analyzed via two-way correlation tables and chi-square analysis. RESULTS: Analysis revealed a relatively high level of inaccuracy of Tuskegee study knowledge and HIV. Influences of these topics in relation to willingness to participate in research and overall perceptions of medical research were minimal. However, there were associations indicating that individuals with moderate or greater knowledge of the Tuskegee Study were less likely to participate in research if free medical care was offered when compared to individuals who knew little or nothing regarding the study. CONCLUSIONS: In order to improve the likelihood of minority participation, the medical research community should tailor their recruitment efforts to take into account common beliefs in the African American community concerning medical research.PUBLIC HEALTH SIGNIFICANCE: The data have implications related to the ability to garner trust between the African American and medical research communities, with the ultimate goal to improve likelihood of minority participation in medical research. With a significant degree of misconceptions conce