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        Immune correlates of protection for dengue: State of the art and research agenda

        Katzelnick, Leah C.,Harris, Eva,Baric, Ralph,Coller, Beth-Ann,Coloma, Josefina,Crowe Jr., James E.,Cummings Jr., Derek A.T.,Dean Jr., Hansi,de Silva Jr., Aravinda,Diamond Jr., Michael S.,Durbin Jr., A Elsevier 2017 Vaccine Vol.35 No.36

        <P><B>Abstract</B></P> <P>Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the “<I>Summit on Dengue Immune Correlates of Protection</I>”, held in Annecy, France, on March 8–9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.</P>

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        Characterization of Large Structural Genetic Mosaicism in Human Autosomes

        Machiela, Mitchell J.,Zhou, W.,Sampson, Joshua N.,Dean, Michael C.,Jacobs, Kevin B.,Black, A.,Brinton, Louise A.,Chang, I.S.,Chen, C.,Chen, C.,Chen, K.,Cook, Linda S.,Crous Bou, M.,De Vivo, I.,Doherty University of Chicago Press [etc.] 2015 American journal of human genetics Vol.96 No.3

        Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10<SUP>-31</SUP>) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

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