Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia.
Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia.
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DOI：
10.3389/fgene.2021.737741
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发表时间：
2021
影响因子：
3.7
通讯作者：
Meller R
中科院分区：
文献类型：
--
作者：
Gee BE;Pearson A;Buchanan-Perry I;Simon RP;Archer DR;Meller R
通过全转录组 RNA 测序来量化从稳态镰状细胞性贫血 (SCA) 和对照受试者收集的全血样本中 RNA 表达的变化。儿科 SCA 和对照受试者是从亚特兰大 (GA) 的医院系统招募的，并同意进行 RNA 测序。 RNA 测序是在 Ion Torrent S5 测序仪上使用 Ion Total RNA-seq v2 协议进行的。数据与 hg19 参考基因组进行比对，并在 Partek Genomics studio 软件包 (v7.0) 中进行分析。 SCA 和对照之间有 223 个基因存在差异表达（± 1.5 倍变化 FDR p < 0.001），441 个基因显示差异转录表达（± 1.5 倍 FDR p < 0.001）。差异表达的 RNA 富含血红蛋白相关基因和泛素-蛋白酶体途径基因。进一步分析显示，SCA 中的 γ 珠蛋白基因表达较高（HBG1 的 33 倍和 HBG2 的 49 倍，FDR p < 0.05），这与血红蛋白 F 蛋白水平无关。 eQTL 分析发现新型非编码 RNA RYR2 基因中的 SNP 对 HBG1 和 HBG2 表达水平具有潜在的调节作用。基因表达相关性鉴定出 JHDM1D-AS1(KDM7A-DT)（一种与血管生成相关的非编码 RNA），增强了 GATA1 并降低了 JAK-STAT 信号传导，从而与 HBG1 和 HBG2 mRNA 水平相关。这些数据表明了胎儿血红蛋白调节的新调节机制，这可能为 SCA 提供创新的治疗方法。
Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.
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影响因子：
2.7
作者：
Raghavachari N;Barb J;Yang Y;Liu P;Woodhouse K;Levy D;O'Donnell CJ;Munson PJ;Kato GJ
通讯作者：
Kato GJ
长的非编码RNA JHDM1D-AS1通过调节养分饥饿而调节血管生成来促进肿瘤的生长。
影响因子：
5.3
作者：
Kondo A;Nonaka A;Shimamura T;Yamamoto S;Yoshida T;Kodama T;Aburatani H;Osawa T
通讯作者：
Osawa T
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
11.2
作者：
Jickling, Glen C.;Stamova, Boryana;Ander, Bradley P.;Zhan, Xinhua;Tian, Yingfang;Liu, Dazhi;Xu, Huichun;Johnston, S. Claiborne;Verro, Piero;Sharp, Frank R.
通讯作者：
Sharp, Frank R.
影响因子：
3.7
作者：
Robert F;Pelletier J
通讯作者：
Pelletier J