Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Candidate SNPs for carcass and meat traits in Nelore animals and in their crosses with Bos taurus

The objective of this work was to evaluate the effects of single-nucleotide polymorphisms (SNPs) in the genes IGF1 (AF_017143.1: g. 198C>T), MSTN (AF_320998.1:g. 433C>A), MYOD1 (NC_007313:g. 1274A>G) and MYF5 (NC_007303:g.1911A>G) on carcass and meat traits in Nelore (Bos indicus) and Nelore x B. taurus. A total of 300 animals were genotyped and phenotyped for rib eye area (REA), backfat thickness (BT), intramuscular fat (IF), shear force (SF) and myofibrillar fragmentation index (MFI). The effects of allele substitution for each SNP were estimated by regression of the evaluated phenotypes on the number of copies of a particular allele using the general linear model. The polymorphism at IGF1 was non-informative in Nelore animals. In crossbred animals, the IGF1 C allele was associated with greater REA. However, this relation was not significant after Bonferroni correction for multiple testing. The A allele of the MSTN polymorphism was absent in Nelore cattle and was only found in two crossbred animals. The polymorphisms of MYOD1 and MYF5 were little informative in Nelore animals with G allele frequency of 0.097 and A allele frequency of 0.031, respectively. These markers show no association with the analyzed traits in the total sample of evaluated animals

Current strategies for the assessment and evaluation of genetic diversity in chicken resources

Chicken genetic resources comprise a wide range of breeds and populations including red jungle fowl (the assumed progenitor of all domestic breeds), native and fancy breeds, middle level food producers, industrial stocks and specialised lines. Based on the suggestion that the more distant a breed or population is the more likely it is to carry unique genetic features, the assessment of genetic distances by means of molecular marker information may provide useful information for initial evaluation of chicken genetic resources. During the last two decades several molecular marker classes have become available. Variable numbers of tandem repeat loci, in particular microsatellites, have been successfully used in chicken diversity studies. Genetic diversity measures using the highly polymorphic variable number of tandem repeat lociyield reliable and accurate information for the study of genetic relationships between chicken populations. First results of the European project on chicken biodiversity (AVIANDIV) obtained from microsatellite typing in DNA pools of 51 diverse chicken breeds showed that jungle fowl populations, traditional unselected breeds and broiler lines appear to be widely heterogeneous populations that may include a large portion of the genetic diversity of the tested breeds. In contrast, highly selected strains (layers and experimental lines) are characterised by a lower polymorphism. They behave as outliers from the set of breeds sampled. Single nucleotide polymorphism is a new and very promising molecular marker system which offers opportunities to assess the genetic diversity in farm animal species differently by investigating the mode and extent of changes in certain positions in the genome

Establishing reference values for central blood pressure and its amplification in a general healthy population and according to cardiovascular risk factors

Estimated central systolic blood pressure (cSBP) and amplification (Brachial SBP-cSBP) are non-invasive measures potentially prognostic of cardiovascular (CV) disease. No worldwide, multiple-device reference values are available. We aimed to establish reference values for a worldwide general population standardizing between the different available methods of measurement. How these values were significantly altered by cardiovascular risk factors (CVRFs) was then investigated.AtCor Medical via an unrestricted gran