The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Recreational fishery as a conservation tool for endemic Dolly Varden Salvelinus malma miyabei in Lake Shikaribetsu, Japan

Recreational angling is a popular leisure activity globally and can be a threat or useful conservation tool depending on the management strategy. Miyabe charr Salvelinus malma miyabei is an endemic fish that inhabits Lake Shikaribetsu, and a management program was established to harmonise recreational fishery and conservation. To examine the suitability of this program, population assessment was conducted with the cooperation of anglers. The population size in 2014 as assessed by tag-and-release angling was estimated to be 105,300 [95% confidence interval (CI) 37,300-178,600], much higher than the reported estimate in 1995. Further, angling mortality was estimated to be quite low. Moreover, no decreasing population trend was detected on analysing 8 years of anglers' catch data. Consequently, angling has facilitated stock assessments of Miyabe charr under the current program. This case is a good example of recreational angling acting as a conservation tool under appropriate management

Long-term shifts in the growth and maturation size of Miyabe charr Salvelinus malma miyabei

Overfishing can affect life history traits, resulting in population collapse and oftentimes a decrease in length-at-age and maturation size in fish populations. However, little is known about the recovery mechanisms and time scales of these traits in exploited wild populations. In the study reported here, we documented long-term shifts in growth and mature size in Miyabe charr Salvelinus malma miyabei associated with a history of recreational fishing in Lake Shikaribetsu for approximately 80 years. Downsizing in the charr was observed when the charr population collapsed due to intensive recreational fishing. However, subsequent moratoriums and the introduction of fishing regulations, especially the implementation of a catch-and-release policy, during the following 10-30 years facilitated the recovery of population size, length-at-age and mature fish size. This study provides important insights into the biological changes and required recovery time scales of a heavily harvested population and supports management and conservation strategies.北海道然別湖に生息するミヤベイワナの成長解析を行い、約80年にわたる漁獲圧と成長や成熟魚サイズの変化の関係について検討した。その結果、過剰な遊漁による漁獲圧の上昇により、ミヤベイワナの成長が鈍化し成熟魚が小型化したと考えられた。しかし、禁漁や遊漁規制の導入により、現在は乱獲状態にあった時期と比べて資源が回復し、約10年から30年で個体の成長と成熟魚サイズが回復したことが示唆された

Species-specific relationship between angler catch and satisfaction among anglers targeting salmonid fishes in Hokkaido lakes, Japan

遊漁対象種の希少性や生物学的特性の違いに着目し，北海道然別湖，朱鞠内湖および洞爺湖における遊漁者を対象に，遊漁者の満足度と釣果の関係を比較した。その結果，1）希少魚の釣果は1尾の釣果が遊漁者の満足度を大きく高める，2）希少魚の釣果はその魚種が1番の狙いの魚種でなくとも遊漁者の満足度に影響を与えうる，3）大型に育つ遊漁対象種では釣獲尾数よりも体サイズに満足度の主眼がおかれる，4）遊漁対象種に食用としての価値が高い場合，遊漁者にとって満足といえる釣獲尾数はより多くなる，という傾向が明らかになった。Recreational angling is a dominant use of inland fish resources. Since recreational angling is a leisure-based activity, the stock manager must meet two objectives: 1) maintain fish stocks, and 2) maximize angler satisfaction with limited catch. To achieve these goals, it is important to evaluate the relationship between angler satisfaction and catch in order to construct a management strategy, because catch is one of the most important connections between fish stock and angler satisfaction. In this study, the relationships of four angling target species which have different biological and social traits were investigated. The results of a questionnaire survey of 639 anglers in total revealed four types of orientation: 1) the catch of endemic target fish strongly enhances angler satisfaction, 2) the existence of endemic fish increases angler satisfaction for all anglers, 3) fish size has a greater influence than number of fish for anglers who target fish that grow larger (i.e. trophy anglers), and 4) anglers desire more fish when the target fish has higher value as a food (i.e. consumption orientation). For the sustainable use of fish stocks for recreational angling, not only the biological traits of stocks but also anglers' orientation toward catch should be considered