microsatellite

微卫星
  • 文章类型: Journal Article
    为了实现经济增强的突变,生产,和两个埃及cow豆品种的营养特征,Dokki331和Kaha1,采用不同剂量的γ辐射。此外,该方法有助于使用简单序列重复(SSR)分析区分这些突变.
    对两个不同的of豆品种进行了50至300Gy的不同剂量的γ辐射。为了分析辐射的影响,使用随机完全区组设计种植来自两个品种的未辐照和辐照种子。这个实验进行了六代,即M1、M2、M3、M4、M5和M6,从2017年4月开始,一直持续到2022年。在各种辐射剂量中,当暴露于150Gy的剂量时,品种Kaha1产生了有希望的性状,而品种Dokki331在暴露于300Gy剂量时表现出良好的性状。这些性状被进一步培养和研究直到M6代。
    在两个埃及cow豆品种中诱导突变,Kaha1和Dokki331经受不同剂量的γ辐射(0、50、100、150、200、250和300Gy)。观察到形态和遗传变异,Kaha1的剂量为150Gy,Dokki331的剂量为300Gy。Kaha1(光束1)中的突变导致侏儒症,改变的叶子形状,早期开花,增加了花梗,豆荚,和豆荚种子编号,最终提高种子产量和种植面积。在Dokki331中,突变主要影响豆荚的颜色,产生带有马赛克种子的绿棕色豆荚,将黑色和灰色种子与马赛克种子分开。这些突变导致种子的营养价值增加,包括较高的氮含量,总游离氨基酸,粗蛋白,总碳水化合物,和总糖。使用20个微卫星标记评估了七个the豆突变的遗传多样性。分析显示总共有60个等位基因,每个基因座平均有三个等位基因。等位基因频率范围为0.2857至1.0,平均为0.6036。基因多样性从0.0到0.8163不等,而杂合度大多为零,除了一个引物(VM37),平均0.0071。多态信息含量(PIC)范围为0.7913~0.0,平均为0.4323。标记指数值范围为0.36至0.0,平均值为0.152。总的来说,我们的研究结果表明,利用伽马射线成功地诱导了埃及cow豆品种的突变,从而提高了产量特性和营养价值。
    辐射作为物理诱变剂因其有效性而备受推崇,负担能力,速度,和诱导突变的安全性。利用伽马射线,我们成功地衍生出了一种名为beam1突变的新型of豆品种,已获得埃及农业部的批准。
    UNASSIGNED: In order to achieve mutations with enhanced economic, productive, and nutritional characteristics in the two Egyptian cowpea varieties, Dokki 331 and Kaha 1, the application of gamma irradiation at different doses is employed. Additionally, this method aids in distinguishing between these mutations using simple sequence repeat (SSR) analysis.
    UNASSIGNED: Two different cowpea cultivars were subjected to varying doses of gamma radiation ranging from 50 to 300 Gy. In order to analyze the effects of radiation, both unirradiated and irradiated seeds from both cultivars were planted using a randomized complete block design. This experiment was conducted over a span of six generations, namely M1, M2, M3, M4, M5, and M6, starting from April 2017 and continuing until 2022. Among the various radiation doses, the cultivar Kaha 1 produced promising traits when exposed to a dose of 150 Gy, while the cultivar Dokki 331 showed favorable traits when exposed to a dose of 300 Gy. These traits were further cultivated and studied until the M6 generation.
    UNASSIGNED: Induced mutations in two Egyptian cowpea varieties, Kaha 1 and Dokki 331, are subjected to varying doses of gamma radiation (0, 50, 100, 150, 200, 250, and 300 Gy). Morphological and genetic variations were observed, with mutations being induced at doses of 150 Gy for Kaha 1 and 300 Gy for Dokki 331. The mutation in Kaha 1 (beam 1) resulted in dwarfism, altered leaf shape, early flowering, increased peduncles, pods, and pod seed numbers, ultimately leading to enhanced seed production and acreage productivity. In Dokki 331, the mutations primarily affected pod color, resulting in greenish-brown pods with mosaic seeds, segregating black and gray seeds from the mosaic ones. These mutations led to an increase in the nutritional value of the seeds, including higher nitrogen content, total free amino acids, crude protein, total carbohydrates, and total sugars. The genetic diversity of the seven cowpea mutations was assessed using 20 microsatellite markers. The analysis revealed a total of 60 alleles, with an average of three alleles per locus. The allele frequency ranged from 0.2857 to 1.0, with an average of 0.6036. Gene diversity varied from 0.0 to 0.8163, while the heterozygosity was mostly zero, except for one primer (VM 37) with an average of 0.0071. The polymorphic information content (PIC) ranged from 0.7913 to 0.0, with an average of 0.4323. The Marker Index value ranged from 0.36 to 0.0, with an average of 0.152. Overall, our findings demonstrate the successful induction of mutations in Egyptian cowpea varieties using gamma rays, resulting in improved yield characteristics and nutritional value.
    UNASSIGNED: Radiation as a physical mutagen is highly regarded for its effectiveness, affordability, speed, and safety in inducing mutations. Utilizing gamma rays, we successfully derived a novel cowpea variety called beam 1 mutation, which has gained approval from the Egyptian Ministry of Agriculture.
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  • 文章类型: Journal Article
    金子花是春季短命金子花属中亚热带地区唯一分布的物种。人类的广泛开发和栖息地的破坏导致了G.kiangnanense种群的迅速减少。本研究利用微卫星标记分析了江西现存种群的遗传多样性和结构,并推导了历史种群事件。
    共有来自8个现存G.kiangnanense种群的143个人,包括安徽省的两个人口和浙江省的六个人口,使用21对微卫星标记进行了分析。使用Cervus计算遗传多样性指数,GENEPOP,GenaLEX.利用遗传距离(UPGMA)评估种群结构,主坐标分析(PCoA),贝叶斯聚类方法(结构),和分子变异方差分析(AMOVA)。使用DIYABC推断种群历史事件。
    所研究的G.kiangnanense种群表现出低水平的遗传多样性(He=0.179,I=0.286),但遗传分化程度高(FST=0.521)。种群间基因流(Nm)的平均值为1.082,表明通过花粉扩散进行的基因交换普遍存在。系统地理学分析表明,江南菜的种群分为两个谱系,浙江(ZJ)和安徽(AH)。这两个谱系被黄山-天目山山脉隔开。AMOVA分析显示,总遗传变异的36.59%发生在两组之间。ZJ谱系进一步分为杭州(ZJH)和诸暨(ZJZ)谱系,被龙门山和富春河隔开。DIYABC分析表明,ZJ和AH谱系在5.592ka分离,可能是由于全新世气候变化和人类活动的影响。随后,ZJZ谱系在2.112ka左右与ZJH谱系不同。考虑到kiangnanense的有限分布及其谱系之间的显著遗传分化,应实施原位和异地保护策略,以保护G.kiangnanense的种质资源。
    UNASSIGNED: Gymnospermium kiangnanense is the only species distributed in the subtropical region within the spring ephemeral genus Gymnospermium. Extensive human exploitation and habitat destruction have resulted in a rapid shrink of G. kiangnanense populations. This study utilizes microsatellite markers to analyze the genetic diversity and structure and to deduce historical population events of extant populations of G. kiangnanense.
    UNASSIGNED: A total of 143 individuals from eight extant populations of G. kiangnanense, including two populations from Anhui Province and six populations from Zhejiang Province, were analyzed with using 21 pairs of microsatellite markers. Genetic diversity indices were calculated using Cervus, GENEPOP, GenALEX. Population structure was assessed using genetic distance (UPGMA), principal coordinate analysis (PCoA), Bayesian clustering method (STRUCTURE), and molecular variation analysis of variance (AMOVA). Population history events were inferred using DIYABC.
    UNASSIGNED: The studied populations of G. kiangnanense exhibited a low level of genetic diversity (He = 0.179, I = 0.286), but a high degree of genetic differentiation (FST = 0.521). The mean value of gene flow (Nm ) among populations was 1.082, indicating prevalent gene exchange via pollen dispersal. Phylogeographic analyses suggested that the populations of G. kiangnanense were divided into two lineages, Zhejiang (ZJ) and Anhui (AH). These two lineages were separated by the Huangshan-Tianmu Mountain Range. AMOVA analysis revealed that 36.59% of total genetic variation occurred between the two groups. The ZJ lineage was further divided into the Hangzhou (ZJH) and Zhuji (ZJZ) lineages, separated by the Longmen Mountain and Fuchun River. DIYABC analyses suggested that the ZJ and AH lineages were separated at 5.592 ka, likely due to the impact of Holocene climate change and human activities. Subsequently, the ZJZ lineage diverged from the ZJH lineage around 2.112 ka. Given the limited distribution of G. kiangnanense and the significant genetic differentiation among its lineages, both in-situ and ex-situ conservation strategies should be implemented to protect the germplasm resources of G. kiangnanense.
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  • 文章类型: Journal Article
    在这项工作中,我们分析了小麦的形态和遗传结构,T.capitatum及其杂种T.×rohlenae来自三个同位种群。形态计量学研究表明,亲本及其杂种表现出连续的形态变异,杂种恰好位于父母之间。遗传分析显示,在形态上鉴定为T.×rohlenae的植物是可育的杂种,产生以后代杂种为主的杂种群。这表明渗入,而不是物种形成,是这些植物物种之间杂交的更可能的结果。两个物种之间的基因流的程度和方向在三个同位位置之间显着不同。在Trilj地区,这显然是单向的,以T.Capetatum发挥主导作用。在西奇沃地区,基因流稍微不对称,有利于头花T.的遗传背景,而在Sliven现场,它在相反的方向上是完全不对称的。在Trilj地区观察到了单向基因流动的极端情况,在该地区,在形态上鉴定为T.montanum的植物无法在遗传上与T.capetatum区分开。这表明种间杂交发生在很久以前,导致渗入和神秘杂交,物种边界模糊并产生进化噪声。
    In this work, we analyzed the morphology and genetic structure of Teucrium montanum, T. capitatum and their hybrid T. × rohlenae from three syntopic populations. A morphometric study showed that the parents and their hybrids exhibited continuous morphological variation, with the hybrid positioned exactly between the parents. Genetic analysis revealed that plants morphologically identified as T. × rohlenae are fertile hybrids that produce hybrid swarms dominated by later-generation hybrids. This suggests that introgression, rather than speciation, is the more likely outcome of hybridization between these plant species. The extent and direction of gene flow between the two species differed markedly between the three syntopic localities. At the Trilj locality, it was clearly unidirectional, with T. capitatum playing the dominant role. At the Sićevo locality, gene flow was slightly asymmetric, favoring the genetic background of T. capitatum, while at the Sliven site, it was completely asymmetric in the opposite direction. The extreme case of unidirectional gene flow was observed at the Trilj locality where plants morphologically identified as T. montanum could not be genetically distinguished from T. capitatum. This suggests that interspecific hybridization occurred long ago, leading to introgression and cryptic hybrids, blurring of species boundaries and generating evolutionary noise.
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  • 文章类型: Journal Article
    这项研究是表征Rhodusuyekii基因组并研究微卫星标记及其应用于野生种群遗传结构的开发的第一份报告。基因组组装基于PacBioHiFi和IlluminaHiSeq配对末端测序,导致了R.uyekii的基因组组装草案。将草图基因组组装成2652个重叠群。组件的完整性评估表明草案组件的质量很高,Verbrata数据库中有3259个完整的BUSCOs(97.2%)。在蛋白质数据库中注释了总共31,166个预测的蛋白质编码基因。系统发育树显示,杜氏毛虫是巨毛甲虫的近亲但不同的亲戚。在10个鱼类基因组中,有显著的基因家族扩增(8-2387)和收缩(16-2886)。通过21个多态性标记扩增的等位基因的平均数量为6至23个,平均PIC值为0.753,这将对进化和遗传分析有用。利用群体遗传分析,我们分析了来自6个种群的120个个体的遗传多样性和遗传结构。每个群体的平均等位基因数在7.6到9.9之间,观察到的杂合性在0.496到0.642之间,预期杂合性在0.587到0.783之间。主成分的判别分析根据分析方法,人口分为三个群体(BS与DCvs.GG,GC,MS,DC)。总之,我们的研究为比较基因组学提供了有用的资源,系统发育,和未来的人口研究。
    This study is the first report to characterize the Rhodus uyekii genome and study the development of microsatellite markers and their markers applied to the genetic structure of the wild population. Genome assembly was based on PacBio HiFi and Illumina HiSeq paired-end sequencing, resulting in a draft genome assembly of R. uyekii. The draft genome was assembled into 2652 contigs. The integrity assessment of the assemblies indicates that the quality of the draft assemblies is high, with 3259 complete BUSCOs (97.2%) in the database of Verbrata. A total of 31,166 predicted protein-coding genes were annotated in the protein database. The phylogenetic tree showed that R. uyekii is a close but distinct relative of Onychostoma macrolepis. Among the 10 fish genomes, there were significant gene family expansions (8-2387) and contractions (16-2886). The average number of alleles amplified by the 21 polymorphic markers ranged from 6 to 23, and the average PIC value was 0.753, which will be useful for evolutionary and genetic analysis. Using population genetic analysis, we analyzed genetic diversity and the genetic structures of 120 individuals from 6 populations. The average number of alleles per population ranged from 7.6 to 9.9, observed heterozygosity ranged from 0.496 to 0.642, and expected heterozygosity ranged from 0.587 to 0.783. Discriminant analysis of principal components According to the analysis method, the population was divided into three populations (BS vs. DC vs. GG, GC, MS, DC). In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of R. uyekii.
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  • 文章类型: Editorial
    冷杉属广泛分布于世界各地,对林业具有重要意义。由于叶绿体通常是单亲遗传的,它们是解决基因流动等特定科学问题的重要工具,亲子关系,迁移和,总的来说,进化分析。在针叶树中建立的细胞器遗传标记相当限于RFLP标记,更多的劳动力和时间密集,与SSR标记相比。使用QUIAGENCLCWorkbench23.03,我们将来自不同冷杉物种的两个叶绿体基因组(NCBI种质:NC_039581,NC_042778,NC_039582,NC_042410,NC_035067,NC_062889,NC_042775,NC_057314,NC_041464,MH706244,MH047653潜在使用NCBI引物Blast服务器应用程序进行正向和反向引物的进一步选择和开发。在这篇文章中,我们为各种冷杉物种引入了一个非常多态的SSR标记集,这对其他针叶树属可能有用,比如Cedrus,松树,Pseudotsuga或Picea。总的来说,17个cpSSRs显示出可靠的扩增和多态性,总共检测到68个单倍型。在测试的冷杉属中扩增了所有17个cpSSR。在其他测试物种中,除了Taxusbaccata,至少一个引物是多态的。
    The genus Abies is widely distributed across the world and is of high importance for forestry. Since chloroplasts are usually uniparentally inherited, they are an important tool for specific scientific issues like gene flow, parentage, migration and, in general, evolutionary analysis. Established genetic markers for organelles in conifers are rather limited to RFLP markers, which are more labour and time intensive, compared with SSR markers. Using QUIAGEN CLC Workbench 23.03, we aligned two chloroplast genomes from different Abies species (NCBI accessions: NC_039581, NC_042778, NC_039582, NC_042410, NC_035067, NC_062889, NC_042775, NC_057314, NC_041464, MH706706, MH047653 and MH510244) to identify potential SSR candidates. Further selection and development of forward and reverse primers was performed using the NCBI Primer Blast Server application. In this article, we introduce a remarkably polymorphic SSR marker set for various Abies species, which can be useful for other conifer genera, such as Cedrus, Pinus, Pseudotsuga or Picea. In total, 17 cpSSRs showed reliable amplification and polymorphisms in A. grandis with a total of 68 haplotypes detected. All 17 cpSSRs amplified in the tested Abies spp. In the other tested species, except for Taxus baccata, at least one primer was polymorphic.
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  • 文章类型: Journal Article
    背景:串联重复是基因组DNA中串联重复的特定序列,存在于所有生物体中。在TR的子类别中,我们有卫星重复,它分为宏观卫星,小型卫星,和微型卫星,是最后两个特别感兴趣的,因为它们可以由于生物体的不稳定性而识别生物体之间的多态性。目前,大多数挖掘工具专注于简单序列重复(SSR)挖掘,只有少数可以识别编码区的SSR。
    结果:我们基于用C和Python编写的新滑动窗口算法,开发了一种名为SATIN(Micro和MiniSATelliteIdentifatioN工具)的微卫星采矿软件。通过解决现有工具的局限性,它代表了一种新的SSR挖掘方法,特别是在编码区SSR挖掘中。SATIN可在https://github.com/labgm/SATIN获得。git.它被证明是完美和复合SSR采矿的第二快。它可以识别来自编码区的SSR加上基序大小大于6的SSR。除了SSR采矿,SATIN还可以分析来自预定组的编码区的SSRs多态性,并在每个基因的基础上鉴定它们之间差异丰富的SSR。要验证,我们分析了来自两组大肠杆菌(K12和O157)的SSR,并将结果与来自编码区的5个已知SSR进行了比较。SATIN从237个基因中鉴定出所有5个SSR,其中至少有一个SSR。
    结论:SATIN是一种新颖的微卫星搜索软件,它利用基于数字列表的创新滑动窗口技术进行重复区域搜索,以识别完美的,和复合SSR,同时产生可理解和可分析的输出。它是一种能够使用fasta或GenBank格式的文件作为微型卫星采矿的输入的工具,还能够识别GenBank文件的编码区中存在的SSR。总之,我们希望SATIN能够帮助识别潜在的SSR用作遗传标记。
    BACKGROUND: Tandem repeats are specific sequences in genomic DNA repeated in tandem that are present in all organisms. Among the subcategories of TRs we have Satellite repeats, that is divided into macrosatellites, minisatellites, and microsatellites, being the last two of specific interest because they can identify polymorphisms between organisms due to their instability. Currently, most mining tools focus on Simple Sequence Repeats (SSR) mining, and only a few can identify SSRs in the coding regions.
    RESULTS: We developed a microsatellite mining software called SATIN (Micro and Mini SATellite IdentificatioN tool) based on a new sliding window algorithm written in C and Python. It represents a new approach to SSR mining by addressing the limitations of existing tools, particularly in coding region SSR mining. SATIN is available at https://github.com/labgm/SATIN.git . It was shown to be the second fastest for perfect and compound SSR mining. It can identify SSRs from coding regions plus SSRs with motif sizes bigger than 6. Besides the SSR mining, SATIN can also analyze SSRs polymorphism on coding-regions from pre-determined groups, and identify SSRs differentially abundant among them on a per-gene basis. To validate, we analyzed SSRs from two groups of Escherichia coli (K12 and O157) and compared the results with 5 known SSRs from coding regions. SATIN identified all 5 SSRs from 237 genes with at least one SSR on it.
    CONCLUSIONS: The SATIN is a novel microsatellite search software that utilizes an innovative sliding window technique based on a numerical list for repeat region search to identify perfect, and composite SSRs while generating comprehensible and analyzable outputs. It is a tool capable of using files in fasta or GenBank format as input for microsatellite mining, also being able to identify SSRs present in coding regions for GenBank files. In conclusion, we expect SATIN to help identify potential SSRs to be used as genetic markers.
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  • 文章类型: Journal Article
    起源于泰国,泰国脊背犬以其独特的毛皮脊而闻名,该毛皮脊沿着其背部向相反的方向生长。泰国的选择性育种和有限的种群导致相关个体之间的紧密近亲繁殖。假定当前的泰国脊背种群经历了遗传多样性的丧失和瓶颈事件。此外,对泰国脊背犬遗传多样性和结构的研究有限。因此,这项研究的目的是评估泰国脊背犬的遗传多样性。微卫星基因分型和线粒体DNAD环序列用于评估来自泰国各个农场的105只泰国脊背犬的遗传多样性。在当前的泰国脊背犬种群中观察到显着的遗传多样性和最少的近亲繁殖。没有观察到瓶颈的迹象,因为泰国脊背所有者之间的遗传物质交换有效地保留了遗传多样性。此外,这项研究中的遗传参数支持动物的主人与主人交换交配计划.为了维持泰国脊背犬的遗传多样性,使用遗传参数来管理遗传亲密关系,同时保持品种特征是必不可少的。这些数据对于确保人口稳定至关重要,这对于长期保护和有效的人口管理至关重要。
    Originating in Thailand, the Thai Ridgeback dog is known for its unique fur ridge that grows in the opposite direction along its back. Selective breeding and a limited populations in Thailand have led to significant close inbreeding among related individuals. The current Thai Ridgeback population is assumed to have experienced a loss of genetic diversity and bottleneck events. Furthermore, studies on the genetic diversity and structure of Thai Ridgeback dogs are limited. Therefore, the aim of this study was to assess the genetic diversity in Thai Ridgeback dogs. Microsatellite genotyping and mitochondrial DNA D-loop sequences were used to assess genetic diversity in 105 Thai Ridgeback dogs from various farms throughout Thailand. Significant genetic diversity and minimal inbreeding were observed in the current Thai Ridgeback population. Signs of bottlenecks were not observed because the exchange of genetic material among Thai Ridgeback owners effectively preserved the genetic diversity. Moreover, the genetic parameters in this study supported owner-to-owner exchanges animals for mating programs. To sustain the genetic diversity of Thai Ridgeback dogs, the use of genetic parameters to manage genetic closeness while preserving breed characteristics is essential. These data are crucial for ensuring demographic stability, which is pivotal for long-term conservation and effective population management.
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  • 文章类型: Journal Article
    微卫星,称为简单序列重复(SSR),是在所有基因组中发现的1到6个核苷酸基序的短串联重复,尤其是真核生物。它们被广泛用作遗传分析和分子育种中的共显性标记。小麦,一个部落的草,包括主要的谷类作物,如面包小麦,大麦,还有黑麦,以及丰富的牧草和草坪草,在全球粮食生产和农业中发挥着至关重要的作用。为了加强遗传工作,加快小麦作物的改良,我们开发了TriticeaeSSRdb,一个集成和用户友好的数据库。它包含来自21个物种的3,891,705个SSR,并提供基于基因组区域的浏览选项,染色体,主题类型,和重复基序序列。高级搜索功能允许基于SSR的染色体位置和长度的个性化搜索。用户还可以探索与SSR相关的基因,设计用于PCR验证的定制引物对,并利用实用工具进行全基因组浏览,序列比对,以及从局部序列进行计算机SSR预测。我们不断更新TriticeaeSSRdb与其他物种和实用工具。我们预计该数据库将极大地促进小麦作物的性状遗传分析并增强分子育种策略。研究人员可以自由访问数据库http://triticeaessrdb.com/。
    Microsatellites, known as simple sequence repeats (SSRs), are short tandem repeats of 1 to 6 nucleotide motifs found in all genomes, particularly eukaryotes. They are widely used as co-dominant markers in genetic analyses and molecular breeding. Triticeae, a tribe of grasses, includes major cereal crops such as bread wheat, barley, and rye, as well as abundant forage and lawn grasses, playing a crucial role in global food production and agriculture. To enhance genetic work and expedite the improvement of Triticeae crops, we have developed TriticeaeSSRdb, an integrated and user-friendly database. It contains 3,891,705 SSRs from 21 species and offers browsing options based on genomic regions, chromosomes, motif types, and repeat motif sequences. Advanced search functions allow personalized searches based on chromosome location and length of SSR. Users can also explore the genes associated with SSRs, design customized primer pairs for PCR validation, and utilize practical tools for whole-genome browsing, sequence alignment, and in silico SSR prediction from local sequences. We continually update TriticeaeSSRdb with additional species and practical utilities. We anticipate that this database will greatly facilitate trait genetic analyses and enhance molecular breeding strategies for Triticeae crops. Researchers can freely access the database at http://triticeaessrdb.com/.
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  • 文章类型: Journal Article
    细胞因子巨噬细胞迁移抑制因子(MIF)基因的功能变体由4个核苷酸的启动子微卫星(-794CATT5-8,rs5844572)定义,并赋予自身免疫性风险,传染性,和肿瘤疾病。我们在这里描述了原型的发现,MIF转录的小分子抑制剂,具有高微卫星重复数的选择性和相应的高基因表达。利用高通量发光接近屏,我们鉴定了1-碳甲氧基-5-甲酰基-4,6,8-三羟基吩嗪(CMFT)以抑制转录因子ICBP90(也称为UHRF1)和MIF-794CATT5-8启动子微卫星之间的功能相互作用。CMFT以-794CATT5-8长度依赖性方式抑制MIFmRNA表达,IC50为470nM,并优先降低高基因型与低基因型MIF表达巨噬细胞中ICBP90依赖性MIFmRNA和蛋白质的表达。RNA表达分析还显示CMFT下调MIF依赖性,炎症基因表达,很少有脱靶代谢毒性的证据。这些发现为推进基于精确的MIF抑制剂用于多种自身免疫和炎性病症的药物基因组开发提供了概念验证。
    Functional variants of the gene for the cytokine macrophage migration inhibitory factor (MIF) are defined by a 4-nucleotide promoter microsatellite (-794 CATT5-8, rs5844572) and confer risk for autoimmune, infectious, and oncologic diseases. We describe herein the discovery of a prototypic, small molecule inhibitor of MIF transcription with selectivity for high microsatellite repeat number and correspondingly high gene expression. Utilizing a high-throughput luminescent proximity screen, we identify 1-carbomethoxy-5-formyl-4,6,8-trihydroxyphenazine (CMFT) to inhibit the functional interaction between the transcription factor ICBP90 (namely, UHRF1) and the MIF -794 CATT5-8 promoter microsatellite. CMFT inhibits MIF mRNA expression in a -794 CATT5-8 length-dependent manner with an IC50 of 470 nM, and preferentially reduces ICBP90-dependent MIF mRNA and protein expression in high-genotypic versus low-genotypic MIF-expressing macrophages. RNA expression analysis also showed CMFT to downregulate MIF-dependent, inflammatory gene expression with little evidence of off-target metabolic toxicity. These findings provide proof-of-concept for advancing the pharmacogenomic development of precision-based MIF inhibitors for diverse autoimmune and inflammatory conditions.
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  • 文章类型: Journal Article
    错配修复(MMR)缺陷继发的微卫星不稳定性(MSI)的特征在于整个基因组的短DNA序列中的插入和缺失(indel)。这些indel可以产生新抗原,是精确免疫拦截的理想目标。然而,当前的新抗原数据库缺乏编码微卫星产生的新抗原的信息。为了解决这个差距,我们介绍了微卫星新抗原发现工具(MONET)。
    MONET通过预测人类基因组编码微卫星序列中的移码突变来鉴定潜在的突变的肿瘤特异性新抗原(neoAgs)。然后,MONET用结合亲和力等关键特征注释这些neoAgs,稳定性,表达式,频率,和使用既定算法的潜在致病性,工具,和公共数据库。用户友好的Web界面(https://monet。mdanderson.org/)便于访问这些预测。
    MONET预测了超过400万和1500万I类和II类潜在移码新G,分别。与现有数据库相比,MONET显示出较高的覆盖率(>85%与<25%)使用一组实验验证的neoAg。
    MONET是免费提供的,用户友好的网络工具,利用公开可用的资源来识别源自微卫星基因座的neoAgs。这种系统生物学方法赋予了精确免疫拦截领域的研究人员权力。
    UNASSIGNED: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET).
    UNASSIGNED: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using established algorithms, tools, and public databases. A user-friendly web interface (https://monet.mdanderson.org/) facilitates access to these predictions.
    UNASSIGNED: MONET predicts over 4 million and 15 million Class I and Class II potential frameshift neoAgs, respectively. Compared to existing databases, MONET demonstrates superior coverage (>85% vs. <25%) using a set of experimentally validated neoAgs.
    UNASSIGNED: MONET is a freely available, user-friendly web tool that leverages publicly available resources to identify neoAgs derived from microsatellite loci. This systems biology approach empowers researchers in the field of precision immune interception.
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