A Preliminary Study of Whole Blood Transcriptome Analysis Using RNA Sequencing in Repetitive Low-Level Blast Exposure in Career Breacher. A Preliminary Study of Whole Blood Transcriptome Analysis Using RNA Sequencing in Repetitive Low-Level Blast Exposure in Career Breacher

Repetitive low-level blast exposure is one of the major occupational health concerns in the US mil-itary service members and law enforcement, and the underlying biological mechanisms remain controversial. Therefore, this study is to identify gene expression using RNA sequencing in the whole blood sample from experienced breachers and unexposed control. We performed experi-mental RNA sequencing using Illumina’s HiSeq 2500 Sequencing System in whole blood samples from 15 experienced breachers and 14 age, sex, race matched unexposed control. We identified 10 significantly dysregulated genes between experienced breacher and unexposed control with FDR corrected < 0.05. One upregulated gene included LINC00996 (long intergenic non-protein coding RNA 996) and 9 downregulated genes including IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin associ-ated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobu-lin heavy variable 4-34). Dysregulated of these genes’ expression are associated with nervous system development and organismal development. The dysregulated gene expression reported in our study is functionally associated with chronic inflammation and immune response in repeti-tive low-level blast exposure, which may have a negative influence on neurological health. Overall design: RNA-seq on blast vs. control

重复低强度爆炸暴露是美国军人与执法人员的主要职业健康隐患之一，其潜在生物学机制仍存在争议。为此，本研究通过RNA测序（RNA sequencing）对资深爆破作业人员与未暴露对照人群的全血样本进行基因表达分析。我们采用Illumina HiSeq 2500测序系统，对15名资深爆破作业人员及14名年龄、性别、种族匹配的未暴露对照人群的全血样本开展RNA测序实验。经错误发现率（FDR, False Discovery Rate）校正后P<0.05，本研究在两组间筛选得到10个显著差异表达基因：其中1个为上调基因LINC00996（长链基因间非编码RNA996，long intergenic non-protein coding RNA 996），剩余9个为下调基因，包括IGLV3-16（免疫球蛋白λ可变区3-16，immunoglobulin lambda variable 3-16）、CD200（CD200分子）、LILRB5（白细胞免疫球蛋白样受体B5，leukocyte immunoglobulin like receptor B5）、ZNF667-AS1（ZNF667反义RNA1，ZNF667 antisense RNA 1）、LMOD1（平滑肌肌动蛋白调节因子1，leiomodin 1）、CNTNAP2（接触蛋白关联蛋白2，contactin associated protein 2）、EVPL（包壳蛋白，envoplakin）、DPF3（双PHD指结构域蛋白3，double PHD fingers 3）以及IGHV4-34（免疫球蛋白重可变区4-34，immunoglobulin heavy variable 4-34）。上述差异表达基因的表达失调与神经系统发育及个体发育密切相关。本研究报道的差异表达基因功能上与重复低强度爆炸暴露引发的慢性炎症及免疫应答存在关联，可能对神经系统健康产生负面影响。整体实验设计：爆炸暴露组与对照组的RNA测序分析。