Summary
Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function.
CARD11
encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used a “cloning-free” saturation genome editing approach in a diploid cell line to simultaneously score 2,542 variants for decreased or increased function in the region of
CARD11
associated with immunodeficiency. We also described an exon-skipping mechanism for CARD11 dominant-negative activity. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.
Monilinia vaccinii-corymbosi (Mvc) is the causal agent of mummy berry in highbush blueberries. The primary inoculum of Mvc consists of ascospores that are discharged from apothecia on overwintered mummified blueberry fruits on the ground below blueberry bushes. Models currently exist in southern climates to predict the emergence of apothecia and ascospore discharge based on growing degree days. In order to better understand the release of primary inoculum in northern climates, apothecial emergence and ascospore discharge was studied in relation to weather variables. A Burkard spore trap was used to collect ascospores in blueberry fields with a history of the disease in 2002, 2003, 2004, and 2009. Peak ascospore discharge was inversely correlated with daily relative humidity, and the majority of ascospores were initially discharged between 61 and 291 growing degree-days (using 5.5°C base) and after 1549 to 1924 chill-hours (above freezing) were attained. The chilling requirement of pseudosclerotia was studied by removing them at different times during the winter months and allowing them to germinate in the laboratory. Additionally, the optimal average apothecial cup diameter in the field was investigated in relationship to ascospore discharge (between 3-7 mm). Finally, we proposed a simplified degree-day model to predict apothecia emergence and ascospore discharge with apothecia emergence timings at several locations from 2007-2010. The information in the study may be used to predict mummy berry apothecium emergence and ascospore discharge and could be incorporated into web-based risk modeling applications with the aim of providing growers useful tools to improve fungicide spray timing.
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