Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Validation of the Residual Feed Intake Model in Brangus Heifers: Determination of the Optimal Days on Feed Interval to Estimate Dry Matter Intake and Average Daily Gain

Brangus cattle are gaining popularity in the Southeast U.S. due to the desirable heat tolerance from their Brahman influence combined with the superior carcass merit aspects of Angus genetics. However, little is known about the optimal evaluation conditions for this hybrid breed when placed on test for Residual Feed Intake (RFI), a heritable measure of feed efficiency that allows improvement in performance without altering carcass traits. To address this, dry matter intake (DMI) was measured on Brangus heifers for 70-d to determine the optimal days on feed required to estimate feed intake and ADG and assess if inclusion of ultrasound measures of carcass merit into the model impact RFI rankings for this breed. The 56-d test period had a regression coefficient of 0.96 (p 2 = 0.94, rp = 0.97 (p p < 0.0001), indicating little change in rank of cattle for DMI compared to a 70-d test. ADG was the limiting factor in determining test duration. Based upon examining only heifers that calved, ultrasound backfat measures should be included in the RFI model to normalize for differences in heifer maturity. Results from this study indicate that a test duration of 56-d is sufficient to accurately estimate DMI in this population. This data indicates on-test duration can be shortened, enhancing the rate of genetic change by reducing cost and increasing the number of animals that can be tested annually

Prehospital use of a modified HEART Pathway and point-of-care troponin to predict cardiovascular events.

Clinical trial registrationclinicaltrials.gov (NCT02709135)