腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)是一种新近发现的自身炎症性疾病,由ADA2双等位基因功能缺失变异导致,属于单基因常染色体隐性遗传疾病。DADA2的临床表型主要包括血管炎及血管病变、低丙种球蛋白血症、...腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)是一种新近发现的自身炎症性疾病,由ADA2双等位基因功能缺失变异导致,属于单基因常染色体隐性遗传疾病。DADA2的临床表型主要包括血管炎及血管病变、低丙种球蛋白血症、淋巴细胞减少、纯红细胞再生障碍性贫血等。DADA2主要通过基因检测确诊,抗肿瘤坏死因子药物及造血干细胞移植是该疾病的主要治疗方案,其发病机制目前尚未完全阐明。本文将重点阐述腺苷脱氨酶2缺乏症的发病机制、诊断及治疗的研究进展。展开更多
目的分析中国人群腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)致病基因频率,为有效开展中国人群DADA2的防控和干预工作提供依据。方法回顾性分析2015年1月至2021年1月于北京智因东方转化医学研究中心有限公司进行全...目的分析中国人群腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)致病基因频率,为有效开展中国人群DADA2的防控和干预工作提供依据。方法回顾性分析2015年1月至2021年1月于北京智因东方转化医学研究中心有限公司进行全外显子组测序的11.1万例原始数据,对ADA2基因致病和可能致病性突变进行携带者筛查,分析ADA2基因杂合突变的类型和等位基因频率。结果发现29种ADA2基因致病和可能致病性杂合突变,其中6种[c.730G>T(p.E244X)、c.1049_c.1061 delAGCTGCCTTACTT(p.K350Tfs*14)、c.940A>T(p.K314X)、c.1239+2(IVS8)T>C、c.1240-1(IVS8)G>A、c.1087C>T(p.Q363X)]既往未见报道,等位基因累计频率为0.58%。人群基因频率最高的为p.F355L(0.5%),其次为p.Y453C(0.014%)和p.P193L(0.013%),其他26种位点均小于0.01%,为罕见突变位点。结论通过筛查丰富了ADA2基因突变谱,明确了中国地区人群的ADA2基因突变的携带率约1/171,推测中国人群的DADA2患病率约1/116964。展开更多
The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space gro...The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space group P21/n and crystal cell parameters:a=1.619 9（3）, b=0.680 5（1）, c=2.802 8（6） nm, β=94.15（3）°; V=3.082（1） nm 3, Z=4, Dc=1.289 g/cm3, Mr=589.22, μ（MoKα）=0.750 mm -1, F（000）=1 268. The structure was refined to R=0.057 8 and wR=0.158 1 for 4 447 observed reflections with I≥2σ（I）. The aquo complex is mononuclear with distorted square-pyramidal coordination.展开更多
The SAGA(Spt-Ada-Gcn5 acetyltransferase)complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation,gene expression,and various developmental processes in e...The SAGA(Spt-Ada-Gcn5 acetyltransferase)complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation,gene expression,and various developmental processes in eukaryotes.However,little is known about the composition and function of the SAGA complex in plants.In this study,we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits but also four plant-specific subunits:three functionally redundant paralogs,SCSI,SCS2A,and SCS2B(SCS1/2A/2B),and a TAF-like subunit,TAFL.Mutations in SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the genes encoding conserved SAGA subunits HAG1 and ADA2B,including delayed juvenile-to-adult phase transition,late flowering,and increased trichome density.Furthermore,we demonstrated that SCS1/2A/2B are required for the function of the SAGA complex in histone acetylation,thereby promoting the transcription of development-related genes.These results together suggest that SCS1/2A/2B are core subunits of the SAGA complex in Arabidopsis.Compared with SAGA complexes in other eukaryotes,the SAGA complexes in plants have evolved unique features that are necessary for normal growth and development.展开更多
文摘腺苷脱氨酶2缺乏症(deficiency of adenosine deaminase 2,DADA2)是一种新近发现的自身炎症性疾病,由ADA2双等位基因功能缺失变异导致,属于单基因常染色体隐性遗传疾病。DADA2的临床表型主要包括血管炎及血管病变、低丙种球蛋白血症、淋巴细胞减少、纯红细胞再生障碍性贫血等。DADA2主要通过基因检测确诊,抗肿瘤坏死因子药物及造血干细胞移植是该疾病的主要治疗方案,其发病机制目前尚未完全阐明。本文将重点阐述腺苷脱氨酶2缺乏症的发病机制、诊断及治疗的研究进展。
文摘The crystal and molecular structure of the title complex, Cu（ada）2（py）2（H2O）（ada=adamantanecarboxylic group, py=pyridine）, C 32H 42CuN2O5, were determined by XRD. It belongs to monoclinic system with space group P21/n and crystal cell parameters:a=1.619 9（3）, b=0.680 5（1）, c=2.802 8（6） nm, β=94.15（3）°; V=3.082（1） nm 3, Z=4, Dc=1.289 g/cm3, Mr=589.22, μ（MoKα）=0.750 mm -1, F（000）=1 268. The structure was refined to R=0.057 8 and wR=0.158 1 for 4 447 observed reflections with I≥2σ（I）. The aquo complex is mononuclear with distorted square-pyramidal coordination.
基金the National Natural Science Foundation of China(32025003)the National Key Research and Development Program of China(2016YFA0500801)from the Chinese Ministry of Science and Technology.
文摘The SAGA(Spt-Ada-Gcn5 acetyltransferase)complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation,gene expression,and various developmental processes in eukaryotes.However,little is known about the composition and function of the SAGA complex in plants.In this study,we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits but also four plant-specific subunits:three functionally redundant paralogs,SCSI,SCS2A,and SCS2B(SCS1/2A/2B),and a TAF-like subunit,TAFL.Mutations in SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the genes encoding conserved SAGA subunits HAG1 and ADA2B,including delayed juvenile-to-adult phase transition,late flowering,and increased trichome density.Furthermore,we demonstrated that SCS1/2A/2B are required for the function of the SAGA complex in histone acetylation,thereby promoting the transcription of development-related genes.These results together suggest that SCS1/2A/2B are core subunits of the SAGA complex in Arabidopsis.Compared with SAGA complexes in other eukaryotes,the SAGA complexes in plants have evolved unique features that are necessary for normal growth and development.
