Grzymski, J. | bioRxiv Science

bioRxiv2019

Population Health Genetic Screening for Tier 1 Inherited Diseases in Northern Nevada: 90% of At-Risk Carriers are Missed

In an unselected population of 23,713 participants who underwent clinical exome sequencing as a part of the Healthy Nevada Project (HNP) in Northern Nevada (Renown Health, Reno, Nevada) from March 15, 2018, to Sept 30, 2018 (Table S1) we find a 1.26% carrier rate for expected pathogenic and likely pathogenic genetic variants in (FH: LDLR, PCSK9, APOB), Hereditary Breast and Ovarian Cancer (HBOC: BRCA1, BRCA2) and Lynch Syndrome (LS: MLH1, MSH2, MSH6, PSM2) with over 90% of carriers undetected under current medical practice. 26% of carriers were found to have advanced disease with 70% first diagnosed before the age of 65. Less than 20% of all carriers had any documented suspicion for inherited genetic disease in the medical record and upon direct follow-up survey under 40% of carriers had family history of relevant disease. A population preventative genetic screening approach for patients under 45 may improve outcomes.\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@1eb1896org.highwire.dtl.DTLVardef@19b2a11org.highwire.dtl.DTLVardef@1e6da81org.highwire.dtl.DTLVardef@1138699org.highwire.dtl.DTLVardef@e9c415_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1:C_FLOATNO O_TABLECAPTIONDemographic Profile of Healthy Nevada Project Participants.\n\nC_TABLECAPTION C_TBL

genetics↗

bioRxiv2019

A real-time multiplexed microbial growth intervalometer for capturing high resolution growth curves

Batch cultures are a low maintenance and routine culturing method used in anaerobic microbiology. Automated tools that measure growth curves from anaerobic microorganisms grown in traditional laboratory glassware, such as Balch-type tubes, are not commercially available. Here we present a new MicrobiAl Growth Intervalometer (MAGI) that captures microbial growth curves through photo conductivity of the medium using a diffused light pattern of specified frequency, rather than photo-attenuation of collimated light used in traditional systems, and is configured with an offset photodetector/emitter to minimize direct impingement of light from the source to improve the resolution of the solutions density. MAGI is operated by software-driven automation and offers investigators a low noise/high gain instrument with capabilities for remote visualization and data acquisition. MAGI is a low maintenance, low cost, and robust platform primarily for anaerobic cultivation and growth monitoring. We demonstrate the utility of this device by first showing that growth rates and generation times in Escherichia coli K-12 are reproducible to previously published results. We then tested MAGI to measure growth curves of an environmental organism, Intrasporangium calvum, under various media compositions. Our results demonstrate that MAGI is a versatile platform to measure growth curves in media under various redox conditions (microaerobic and anaerobic), complex mediums such as Luria-Bertani (LB) broth and minimal media, and for resolving diauxic growth curves when I. calvum is grown on a disaccharide. Lastly, we demonstrate that the device can resolve growth curves for M concentrations of resources that yield low biomass. This research advances the tools available to microbiologist aiming to monitor growth curves in a variety of disciplines, such as environmental microbiology, clinical microbiology, and food sciences.

microbiology↗