No abstract

Viñas, J., Pérez-Serra, A., Vidal, O., Alvarado Bremer, J. R., and Pla, C. 2010. Genetic differentiation between eastern and western Mediterranean swordfish revealed by phylogeographic analysis of the mitochondrial DNA control region. – ICES Journal of Marine Science, 67: 1222–1229. Despite there being evidence of several discrete breeding grounds, Mediterranean populations of swordfish have been considered a single panmictic unit with no genetic substructure. Sequence analysis of the mitochondrial DNA (mtDNA) control region of five Mediterranean locations (n = 251) reveals for the first time a clear genetic differentiation between eastern and western Mediterranean populations. This differentiation was detected only after conducting separate phylogeographic analyses on two previously described mtDNA clades. Although the frequencies of these clades are similar throughout the Mediterranean Sea, the levels of intra-clade genetic variation drop substantially towards the eastern end. This, together with clear differences in past demographic history and uneven migration rates between Mediterranean basins, suggests that the two populations experienced different effects during the Pleistocene. Subsequently, the mtDNA distinctiveness of eastern and western Mediterranean swordfish populations has been maintained probably by homing towards breeding areas.

BackgroundSudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases.Methods and FindingsOur cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively.ConclusionsCardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).