Japanese guidelines for atopic dermatitis 2020.

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice

マイクロサテライトDNAタケイジョウホウ ニ モトヅク ニホンケイ,トクニ ジトリ,ショウコク オヨビ ソノキンエンヒンシュ ノ イデンテキタヨウセイ ト シュウダンコウゾウ

地鶏や小国およびその近縁品種において,品種内に生じた遺伝的差異に関する研究は少ない。本研究はマイクロサテライトDNA多型情報を用いて地鶏,小国およびその近縁品種の遺伝的多様性および集団構造につき分析を行なった。供試鶏として7品種(会津地鶏,岐阜地鶏,土佐地鶏,小国,尾長鶏,東天紅,唐丸)136羽を用い,マイクロサテライト28座位の分析を行なった。その結果,小国系品種(小国,尾長鶏,東天紅)は地鶏や唐丸と比べて高い遺伝的多様性を示した。また,同じ長鳴鶏でも東天紅の遺伝的多様性は高く,唐丸は低い多様性を示した。地鶏は会津地鶏を除き,小国系品種よりも低い多様性を示した。一方,小国系品種はヘテロ接合体率の観察値と期待値の差が大きく,有意な正のF_IS値が得られた。これは,各品種の採取地間で近親交配による遺伝的差異が生じているためと考えられた。各品種間のペアワイズF_STは有意な値を示した。D_AおよびD_AS系統樹において,小国,尾長鶏,東天紅の3品種は1つのクラスターを形成した。一方,地鶏3品種および唐丸は両系統樹で各品種が明確に分かれる結果となった。Structure解析もD_AS系統樹の樹形を支持するものであり,小国,尾長鶏,東天紅は採取地間で遺伝的差異が生じていることが明らかとなった。The genetic relationships between the Jidori, Shokoku and their related breeds, and their genetic population structure are unclear. In this study, microsatellite DNA polymorphisms were used to analyze the genetic relationships and structure among Jidori, Shokoku, and related breeds. A total of 136 individuals of seven breeds, Aizu-Jidori, Gifu-Jidori, Tosa-Jidori, Shokoku, Onagadori, Totenko, and Tomaru, were used in the analyses of the 28 microsatellite loci. High genetic diversity was observed in Shokoku and related breeds. In contrast, low genetic diversity was observed in the Tomaru and Jidori breeds, except in the Aizu-Jidori. A high and positive F_IS value indicating high inbreeding was also detected in Shokoku-related breeds. Among long-crowing breeds, Totenko showed high genetic diversity, but Tomaru showed low genetic diversity. The pairwise F_ST values estimated among breeds were high and significant. In the phylogenetic tree analysis, Shokoku, Onagadori, and Totenko were located in the same cluster in the D_A and D_AS trees. In contrast, three Jidori breeds and Tomaru were clearly separated in each tree. The structure analysis supports the topology of D_AS tree and reveals genetic differentiation among sampling locations in the Shokoku-related breeds as Shokoku, Onagadori and Totenko

マイクロサテライトDNAタガタジョウホウ ニ モトヅク ニホンケイ,トク ニ シャモ オヨビ ソノ キンエンヒンシュ ノ イデンテキタヨウセイ ト シュウダンコウゾウ

軍鶏は多くの日本鶏品種の作出に広く用いられてきたが,それら軍鶏およびその近縁品種間の遺伝的類縁関係や品種内に生じた遺伝的差異については現在でも不明な点が多い。そこで本研究はマイクロサテライトDNA多型情報を用いて軍鶏およびその近縁品種につき分析を行なった。供試鶏として6品種9集団122羽を用い,マイクロサテライト28座位の分析を行なった。その結果,交雑により作出された品種であっても,選抜や品種を維持する過程で遺伝的多様性が低下したと考えられる品種も認められた。特に声良は12座位で多型が認められず,もっとも低い遺伝的多様性を示した。品種間の遺伝的類縁関係は書誌学的,形態学的研究にもとづく説をおおむね支持するものであった。品種間の遺伝的分化の程度は高かった一方,同一品種の別地域集団は系統樹においてクラスターを形成した。軍鶏,薩摩鶏,矮鶏において,品種内に生じた遺伝的差異の程度は異なるものであった。軍鶏は地域集団間で明確な遺伝的差異が認められた一方,矮鶏は地域集団間や内種間で明確な差異は認められなかった。薩摩鶏は地域集団間で差異が認められ,さらに内種によっても遺伝的差異が生じていた。本研究結果より,軍鶏およびその近縁品種間の遺伝的類縁関係は従来説をおおむね支持する一方,品種内に生じる遺伝的差異は品種の維持形態やそれを取り巻く人側の要因により,程度や分集団の単位が異なることが明らかとなった。Shamo is a breed of Japanese native chicken that has been used to establish various modern Japanese native breeds. However, genetic relationships among the breeds derived from the Shamo and their genetic population structure is unclear. In this study, microsatellite DNA polymorphisms were used to analyze the genetic relationship among Shamo and its related breeds. A total of 122 individuals of six breeds (nine populations), Shamo, Ko-Shamo, Hinai-dori, Koeyoshi, Satsuma-dori, and Chabo, were used for the analyses of the 28 loci recommended by ISAG/FAO. In the results, low genetic diversity was observed even in the breeds established by crossbreeding, because of artificial selection and maintenance of these breeds. In particular, the Koeyoshi, which had 12 monomorphic loci, demonstrated the lowest diversity amongst the six breeds. Genetic relationships of these populations were supported by the established theories of their genetic histories. In the phylogenetic tree analysis, local populations of the same breeds were located in the same cluster. However, the star-like topology of the DA tree showed a high and significant genetic differentiation in each population with the exception of two local populations of the Chabo. The degree of genetic differentiation was estimated from local populations of Shamo, Satsuma-dori, and Chabo. A high and significant genetic differentiation was observed in two local populations of the Shamo. In addition, in the Chabo, no genetic differentiation was observed, not only between local populations but also amongst plumage variations. In the Satsuma-dori, differentiations were observed among local populations and plumage variation. In conclusion, the results of this study showed that the degree of genetic differentiation and the unit of population segmentation were influenced by the manner in which the breeds are managed and human factors

マイクロサテライト DNA タケイジョウホウ ニ モトヅク ニホンケイ ジツヨウヒンシュ オヨビ オウベイショウヨウヒンシュ ノ イデンテキタヨウセイ ト シュウダンコウゾウ

日本鶏実用品種3集団(名古屋種,熊本種,天草大王)と欧米商用品種5集団(白色レグホン2集団,ブロイラー[チャンキー],横斑プリマスロック,ロードアイランドレッド)のマイクロサテライトDNA多型情報から各品種内の遺伝的多様性および品種間の類縁関係を明らかにすることを目的とした。名古屋種,熊本種,天草大王を比較すると,天草大王は多様性が高い一方,有意な近親交配が認められた。これは天草大王の復元には3つの品種が用いられ,選抜の過程で近親交配が生じたためと考えられた。名古屋種や熊本種は天草大王と比べて少羽数から回復してからの時間が長く,大規模飼育で維持されているために,近親交配は認められなかったものと考えられた。欧米商用品種は用途や飼育規模,系統により遺伝的多様性や近親交配の程度に差がみられた。白色レグホンを除く6品種の成立にコーチンが関与しているが,それらの品種はDA系統樹において明確なクラスターを形成しなかった 。このことから日本鶏実用品種および欧米商用品種は,その遺伝的背景により大きく2群に分かれ,さらに品種成立後の選抜や維持の過程で遺伝的分化が生じたものと考えられた。Microsatellite DNA polymorphisms of three populations of Japanese meat- type chicken breed (Nagoya, Kumamoto, and Amakusa-Daiou) and five populations of foreign commercial breeds (two populations of White Leghorn, broiler [Chunky], Barred Plymouth Rock, and Rhode Island Red) were analyzed to determine their genetic diversity within populations and relationships among populations. Although high genetic diversity was observed in Amakusa-Daiou, significant inbreeding (positive FIS value) was also observed. The current breed of Amakusa- Daiou was reconstructed from three breeds. Therefore, it is considered that their high genetic diversity was derived from those breeds. However, inbreeding also occurred during the process of reconstruction of Amakusa-Daiou. In contrast, inbreeding was not detected in Nagoya and Kumamoto, which have been maintained for a long time as a large-size population after reconstruction. Foreign commercial breeds showed different degrees of genetic diversity and inbreeding according to their purpose (ex. egg, meat and dual purpose), population size and strain. However, Cochin (traditional meat-type breed originally from China) contributed to most of the current meat-type chicken breeds including Japanese and foreign breeds (six breeds except White Leghorn analyzed in this study). These breeds were not included in the same cluster in phylogenetic tree analysis. The topology of this phylogenetic tree demonstrated two major genetic backgrounds and high genetic differentiation with artificial selection and process of maintaining populations subsequent to construction and reconstruction of breeds

マイクロサテライトDNAタケイジョウホウ ニ モトヅク ニホンケイ,トクニ カンショウヨウヒンシュ ノ イデンテキタヨウセイ ト シュウダンコウゾウ

日本鶏はわが国の貴重な遺伝資源であるにもかかわらず,生産性が低く,その維持を個人愛好家に依存する品種も少なくない。それらの品種の保全においては,遺伝的多様性や集団構造を明らかにすることが必要となる。本研究はマイクロサテライトDNA多型情報から,観賞用品種を中心に解析をおこなった。供試鶏として7品種125羽を用い,マイクロサテライト28座位の分析をおこなった。その結果,愛好家に維持されている観賞用品種であっても,試験研究機関維持集団や銘柄鶏の素材鶏として系統的に維持されている集団と同程度の遺伝的多様性を示すことが明らかとなった。今回分析した7品種すべてに近親交配(正のFIS値)が認められる結果となった。特に蓑曳,蓑曳矮鶏,烏骨鶏は採取地間で遺伝的差異が生じており,DAS系統樹にてサブクラスターが認められた。一方,鶉矮鶏は採取地間の遺伝的差異は認められず,全個体がひとつのクラスターに含まれる結果となった。Japanese native chickens are valuable genetic resource in Japan ; however, their low productivity limits their industrial use and forces dependence on a personal breeder for their maintenance. To conserve these breeds, it is important to clarify their genetic diversity, relationships, and structure. In this study, microsatellite DNA polymorphisms were used to analyze the genetic relationships and structure among ornamental breeds of Japanese native chickens. A total of 125 individuals of seven breeds, Kurokashiwa, Minohiki, Minohiki-Chabo, Uzura-Chabo, Ukokkei, Chahn, and Issun-Chahn were used in analyses of 28 microsatellite loci recommended by ISAG/FAO. The results showed that ornamental breeds maintained by private breeders showed the same level of genetic diversity compared with populations maintained by institutes or breeding stations. Despite high genetic diversity, significant positive FIS values indicating high inbreeding were estimated for all seven breeds analyzed in this study. Furthermore, genetic differentiation among sampling locations was observed in Minohiki, Minohiki-Chabo, and Ukokkei. While sub-clustered structure was observed in the DAS tree for these three breeds, in Uzura-Chabo, genetic differentiation was not observed and all specimens (including those from different sampling locations) were included in the same cluster

マイクロサテライトDNAタケイジョウホウ ニ モトヅク リュウジンジドリ ノ イデンテキタヨウセイ

龍神地鶏は和歌山県の旧龍神村(現在の田辺市)で少数が維持されている集団であり,同地で古くから飼養されているものである。1994年には村内で30数羽が飼養されていたが,近年では個体数が減少し,遺伝的多様性の減少が懸念されている。そこで本研究では1994年および2007年に採血された龍神地鶏(1994年12羽,2007年2集団各18羽,7羽)について,ISAG/FAO推奨の30座位のマイクロサテライトマーカーを用いて遺伝的多様性の経時的な比較と他の日本鶏品種との遺伝的類縁関係を明らかにすることを目的とした。龍神地鶏3集団において30座位中12座位で多型が認められず,5座位で対立遺伝子の消失が認められた。さらに6座位においては遺伝子頻度0.5以上の主要な対立遺伝子が変化していた。その他の座位の対立遺伝子数は2から3の範囲であった。龍神地鶏各集団の平均対立遺伝子数およびヘテロ接合体率は既報の他の日本鶏品種よりも低い値を示した。次に,日本鶏品種内における龍神地鶏の遺伝的な位置を明確にするため,他品種の解析データを加えてD^A遺伝距離にもとづく近隣結合系統樹を作成した。その結果,龍神地鶏は比較に用いたどの品種ともクラスターを形成せず,高いブートストラップ値で他の品種から分かれる結果となった。以上の結果より,龍神地鶏は地域に固有の品種である一方,小集団で長く維持されてきたため近交がすすみ,遺伝的多様性が低くなった集団であると考えられた。今後この品種を維持するためには,現在残されている2つの集団のみならず,県の試験場等を含めて十分な集団サイズを確保し,集団間の系統的維持が必要であると考えられた。Ryujin-Jidori is one of the Japanese native chicken breeds kept in Ryujin village in Wakayama prefecture. Recently, a reduction in population size and in genetic diversity were detected in this breed. In this study, ISAG/FAO recommended 30 microsatellite markers be used to investigate temporal change in genetic diversity and phylogenetic relationships among Ryujin-Jidori and other Japanese native chicken breeds. The Ryujin-Jidori samples were collected in 1994 (n=12) and 2007 (two populations, n=18, 7), respectively. In this analysis, twelve monomorphic loci were observed. Allele loss at five loci and shift of major allele (allele frequency>0.5) at six loci were also observed. In other loci, number of alleles ranged from two to three. Mean number of alleles (MNA) and average expected heterozygosity (H^E) of Ryujin-Jidori populations were lower than previously reported in other Japanese native chicken breeds. No significant difference in MNA was observed between the two Ryujin-Jidori populations. However, a temporal decrease over time in H^E was observed. On the neighbor joining dendrogram based on D^A genetic distance, the Ryujin-Jidori populations were sepa- rated from all other breeds (Gifu-Jidori, Tosa-Jidori, Shokoku and Shamo) with robust bootstrap value. Therefore, it is suggested that Ryujin-Jidori is a unique and valuable genetic resource for Wakayama prefecture. However, to keep Ryujin-Jidori in small population could lead to an affect of genetic drift, intensify inbreeding and decrease genetic diversity

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

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

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