Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease

Congenital Heart Disease (CHD) affects approximately 7-9 children per 1000 live births. Numerous genetic studies have established a role for rare genomic variants at the copy number variation (CNV) and single nucleotide variant level. In particular, the role of de novo mutations (DNM) has been highlighted in syndromic and non-syndromic CHD. To identify novel haploinsufficient CHD disease genes we performed an integrative analysis of CNVs and DNMs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm (TAA). We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed mutation rate testing for DNMs identified in 2,489 parent-offspring trios. Our combined analysis revealed 21 genes which were significantly affected by rare genomic deletions and/or constrained non-synonymous de novo mutations in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in singletons and small cases series, or show new associations with CHD. In addition, a systems level analysis revealed shared contribution of CNV deletions and DNMs in CHD probands, affecting protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes

Torques from manual tools for directional tree felling

Motor-manual tree felling is commonly practiced in many regions of the world. Trees falling in unwanted directions cause severe accidents and extra work in motor-manual logging. Different kinds of manual tools can help force trees to fall in the desired direction, but their capacity are uncertain due to a lack of suitable evaluation methods. Reliable recommendations of felling tools’ limits could help reduce human injuries and damage to property. The objective of this study was, therefore, to develop and evaluate a realistic and convenient method for studying felling tools’ capacity in terms of the potential torque they can generate. A theoretical model of torque components was constructed and the mechanics of the falling tree and of the studied equipment were explained. The developed method uses real trees, which were cut at 1.65 m above stump height to create trial stems. Trial stems were anchored to a neighboring tree and then cut as if they were to be felled. Standardized forces were applied to a forestry jack, felling lever, and wedge, and their effects on the trial stem were recorded by a load cell in the anchoring line. The method proved suitable for the evaluation of forestry jacks, while it needs improvements to evaluate felling levers and wedges thoroughly. Methodological improvements are suggested and practical applications are discussed and demonstrated in terms of the forestry jack’s capacity to deal with trees with unfavorable angles of inclination