DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Report on the survey of freshwater planarians and the water analysis in the Suyoshi River,

The Suyoshi River is a first-class river running from Suyoshi, the eastern hill side of Nagaoka city through the central aerea of the city to join the Shinano-gawa River. The creature having correlationship with the emvironmental factor such as water qualities are known as indicator organizms. Planarian is one of the indicator organisms in freshwater emvironment. This paper reports the survey about the distribution of aquatic indicator organizms, mainly planarians and the water qualities in the Suyoshi River. Cl-, Na+, K+ and Ca2+ at downstream sampling sites were higher than at upstream sites. NO3 -N was 0.19mg/L at sampling site No.4. Three spieces of freshwater planarians; Phagocata vivida, Dugesia japonica and Girardia tigrina were found in the Suyoshi River by different distribution. G. tigrina is the first foreign planarian spieces reported in Niigata Prefecture. This survey was conducted with pre-laboratorial (Prelab) students during May to October in 2016