唐氏综合征胎儿全基因组miRNA表达谱特征及其染色体分布

Characteristics of the whole-genome microRNA expression profiles and chromosome distribution in Down syndrome fetus

目的研究唐氏综合征(DS)胎儿全基因组miRNA表达谱及其编码基因的染色体分布特征。方法采用Illumina深度测序技术对6例DS胎儿(DS组)和6例正常胎儿脐带血(对照组)单个核细胞小RNA测序比对分析,确定DS全基因组miRNA表达谱及其编码基因的染色体分布特征。结果两组共检测到395种miRNA,编码于316个miRNA基因。其中149种miRNA在两组中的表达具有显著性差异(DS组中6种上调,143种下调),有51种miRNA特异性表达于对照组。21号染色体编码的14个miRNA基因在DS组中有1个(miR-802)高表达,4个(let-7c、miR-99a、miR-125b和miR-155)低表达,余下9个在两组样本中均未表达。两组样本miRNA基因表达的染色体分布趋于一致,但miRNA基因表达丰度的分布却不尽相同:DS组主要分布于8、16、17和21号染色体,对照组主要分布于3、8、14、16、17和22号染色体。结论 DS胎儿脐带血单个核细胞具有其特定的miRNA表达谱和染色体分布特征,表达丰度差异分布的染色体编码miRNA可能在DS各临床性状的形成过程中具有重要作用。

Objective To investigate the expression profiles and chromosome distribution characteristics of the whole-genome miRNAs in Down syndrome （DS） fetus. Methods Illumina deep sequencing technology was con- ducted to evaluate the miRNAs expression in 6 pairs of fetal cord blood mononuclear cells （CBMCs） samples from DS fetus （ DS group） and normal fetus （ control group）, the characteristics of miRNA expression and chromosome dis- tribution were confirmed by comparing with human genome. Results Of 395 identified miRNAs encoded by 316 miR- NA genes, 149 miRNAs were significantly differentially expressed （6 miRNAs up-regulated and 143 miRNAs down- regulated in DS group） ,51 miRNAs were specifically expressed in the control fetal CBMCs. For the 14 human chro- mosome 21 （Hsa21） derived miRNA genes, one miRNA （miR-802） was up-regulated in the DS group, and 4 miR- NAs （let-7c, miR-99a, miR-125b and miR-155 ） were down-regulated in the DS group, and other Hsa21-derived miRNA genes were not expressed in two groups. Although the chromosome distribution of expressed miRNA genes was similar in both samples, the chromosome distribution of miRNA expression abundance was different. DS group was major scattered in 8,16,17 and 21 chromosome, while the normal group was major scattered in 3,8,14,16,17 and 21 chromosome. Conclusions The DS fetal CBMCs has its own specific miRNA expression profiles and chromosome dis- tribution characteristics. The miRNAs encoded by the chromosome with differentially distribution of expression abun- dance may play an important role in the development of the DS clinical symptoms.