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

Stethopristes Gilbert 1905

<i>Stethopristes</i> Gilbert, 1905 <p>[New standard Japanese name: Kagaribi-matodai-zoku]</p>Published as part of <i>Koeda, Keita, Sado, Tetsuya, Hata, Harutaka & Fujiwara, Yoshihiro, 2024, Redescription and first Japanese seamount record of Stethopristes eos (Zeiformes; Parazenidae), pp. 579-586 in Zootaxa 5399 (5)</i> on page 580, DOI: 10.11646/zootaxa.5399.5.7, <a href="http://zenodo.org/record/10517572">http://zenodo.org/record/10517572</a&gt

Stethopristes eos Gilbert 1905

<i>Stethopristes eos</i> Gilbert, 1905 <p>[New standard Japanese name: Kagaribi-matodai]</p> <p>Figures 1–3; Table 1</p> <p> <i>Stethopristes eos</i> Gilbert, 1905: 622, fig. 241 (original description; type locality: Pailolo Channel, between Molokai Island and Maui Island, Hawaiian Islands); Pequeño 1989:54 (Chile); Parin 1991: 673; Tyler <i>et al.</i> 2003:15; Mundy 2005: 315 (Hawaiian Islands); Sáez & Lamilla 2017: 97 (Chile).</p> <p> <i>Stethopristes</i> sp.: Koeda <i>et al.</i> 2021: 17, fig. 6A (Ritto Seamount, incorrect depth on p. 17).</p> <p> <b>Material examined.</b> JAMSTEC 106802, 124.2 mm SL, Ritto Seamount (21°37’ N – 21°57’ N, 141°53’ E – 142°13’ E), 519 m depth, 8 Dec. 2020, slurp-gun on <i>KM-ROV</i>, operating from <i>R / V Kaimei</i>; USNM 51626, holotype of <i>Stethopristes eos</i>, 104.1 mm SL, Hawaiian Islands, Pailolo Channel, between Molokai and Maui Islands, and northeast approach, Mokuhooniki Islet, 519–530 m depth, 10 Apr. 1902, <i>R / V Albatross</i>, beam trawl; USNM 51685, paratype, 111.9 mm SL, Hawaiian Islands, vicinity of Kauai Island, Hanamaulu Warehouse, 411–593 m depth, 1 Aug. 1902, <i>R / V Albatross</i>, beam trawl.</p> <p> <b>Description.</b> Counts and measurements of the Japanese specimen and types are given in Table 1.</p> <p>Body oval, strongly compressed laterally. Body depth greatest at dorsal fin origin, least at middle of caudal peduncle. Caudal peduncle depth 1/7.4–7.8 of body depth. Dorsal outline of body generally rounded from snout to dorsal-fin origin, thereafter lowering gradually to middle of caudal peduncle. Ventral outline of head straight, descending obliquely, that of abdomen nearly horizontal, of posterior part of body gradually rising towards middle of caudal peduncle.</p> <p>Head large, bony, with thin skin. Snout short, rounded. Eyes large, diameter greater than half head length. Orbital margin not protruding above dorsal outline of head. Interorbital space smooth. Anterior nostril round. Posterior nostril slit-like, located on dorsal surface just before eye. Dorsal outline of orbit serrate. Mouth terminal, large, strongly oblique ventrally. Posterior end of upper jaw reaching just below anteriormost point of eye. Gill openings large, with membranes on each side fusing mid-ventrally. Lower end of opercular bone with slight posteriorlydirected taper. Premaxillary with wide band of tiny conical teeth; lower jaw teeth of similar size, forming a narrow band. Tongue slightly flattened, long, rounded at tip. Gill rakers shorter than gill filaments, some of former knoblike.</p> <p>...Continued on the next page</p> <p>Body covered with small cycloid scales, except for cheek, top of head, and fins. Ten (nine in USNM 51685) large ridged scutes along midline of abdomen, with continuous sharp ridges centrally. Lateral line elevated from upper end of gill opening, running parallel to dorsal outline of body to just below 3rd dorsal-fin spine, thereafter lowering and becoming parallel to body axis on caudal peduncle. Anus located just before anal-fin origin.</p> <p>Origin of dorsal fin anterior to middle of body, slightly behind base of pectoral fin; spinous and soft-ray portions of dorsal fin low, with long bases; second spine longest in spinous portion; anterior rays of soft-rayed portion shorter than posterior rays; upper part of fin membrane of spinous portion slightly incised, anterior membrane extended slightly as flap; soft-rayed portion slightly incised. Anal-fin origin just below base of 6th dorsal-fin spine; spines short, weak, lacking fin membranes; soft-rayed portion higher and base longer than dorsal fin; anterior half of fin membrane deeply incised. Pectoral fin small, just behind gill opening, its length less than eye diameter. Pelvic fin very large, lacking spines, all rays divided near base; anteriormost point of base slightly anterior to pectoral-fin base; posterior tip of fin nearly reaching middle of anal-fin base when depressed. Caudal fin doubly truncated. Subcaudal rays small, spine-like, four each in upper and lower lobes.</p> <p>Color when alive—Body generally bright reddish-pink with golden reflections and scattered whitish patches. Iris silvery-white. Caudal and pelvic fins red.</p> <p>Color when fresh—Body generally bright red with silvery-white patches. Iris bright red. Dorsal fin red, except membranes of soft-rayed portion white. Anal and caudal fins with pink rays and white membranes. Pectoral fin with reddish translucent rays and translucent membranes. Pelvic fin with red rays and reddish-brown membranes.</p> <p>Color after long term preservation—Body generally pale brown, without prominent markings; ventral portion whitish. Snout, and dorsal and caudal fins brown.</p> <p> <b>Distribution.</b> <i>Stethopristes eos</i> has been recorded from the Hawaiian Islands and Salas y Gómez Ridge, Chile (Gilbert 1905; Sáez and Lamilla 2017). The species is newly recorded here from the Ritto Seamount, West Mariana Ridge (Western Pacific).</p> <p> <b>Habitat.</b> The Japanese specimen was collected near the ridge of Ritto Seamount. Although another individual was observed near the sampling site, the species was not seen in deeper water (to 700 m depth). Therefore, it is conjectured that <i>S. eos</i> occurs in waters near the top of the seamount and adjacent rocky slopes in ca. 500 m depth.</p> <p> <b>Remarks.</b> The genetic analysis of the mitochondrial 12S to 16S ribosome RNA region (1,057 bp) confirmed that the Japanese specimen reported herein clearly differed from all other known Japanese zeiform species, and has been assigned correctly to the family Parazenidae (Fig. 4). The specimen was identified as the rare monotypic species <i>Stethopristes eos</i> based on the following combination of morphological characters: six dorsal-fin spines, ten large ridged scales along the midline of the abdomen with continuous sharp central ridges, and small smooth cycloid scales covering the cheek and body lateral surface, which closely matched those of the types of the species. Previously recorded only from the Hawaiian Islands (type locality) and the Salas y Gómez Ridge, Chile (Gilbert 1905; Sáez & Lamilla 2017), the Japanese specimen represents the first record from the western Pacific Ocean, strongly indicating a much wider distribution of the species across the Pacific region than previously known. The new Japanese names “Kagaribi-matodai-zoku” and “Kagaribi-matodai” are proposed for the genus and species on the basis of the present specimen (JAMSTEC 106802), which exhibited a fiery red color when freshly collected. According to the genetic analysis in this study, the results indicated a monophyletic relationship between the species identified as <i>Parazen pacificus</i>, presently classified under Parazenidae, and instead in Zeniontidae. However, due to the low bootstrap values, indicating low reliability, further taxonomical study within the entire order of Zeniformes is required, encompassing an additional genetic region in future research.</p>Published as part of <i>Koeda, Keita, Sado, Tetsuya, Hata, Harutaka & Fujiwara, Yoshihiro, 2024, Redescription and first Japanese seamount record of Stethopristes eos (Zeiformes; Parazenidae), pp. 579-586 in Zootaxa 5399 (5)</i> on pages 580-584, DOI: 10.11646/zootaxa.5399.5.7, <a href="http://zenodo.org/record/10517572">http://zenodo.org/record/10517572</a&gt