克氏综合征基因表达谱分析  

Gene expression profiling in Klinefelter syndrome

作　　者：赵玉霞[1] 李克秋[1] 景亚青 何晓波[1] 李光[1] 

机构地区：[1]天津医科大学基础医学院医用生物学教研室,300070

出　　处：《国际遗传学杂志》2014年第5期209-215,共7页International Journal of Genetics

基　　金：基金项目：国家自然科学基金（21177091）;天津市科技支撑重点项目（12ZCZDSY03400）

摘　　要：目的 对克氏综合征（Klinefelter syndrome）患者进行基因表达谱分析,探讨其基因差异表达与临床表型之间的关系.方法 采用第二代高通量测序方法对7例克氏综合征患者和7例对照男性外周血全基因组mRNA进行深度测序,运用定量RT-PCR方法对30例克氏综合征患者及30例对照男性进行验证.结果 测序结果根据FDR≤0.001和｜ log2 Ratio≥1 ｜的标准,两组比较存在差异表达基因216个,差异具有统计学意义.其中X染色体基因9个,占4％,与X染色体失活相关的XIST差异表达最明显;常染色体基因207个,占96％,其中NR4A3、ZKSCAN4、HBEGF、EREG、AREG、NR4A2、CCR5差异表达明显.NR4A3主要.与2型糖尿病有关,HBEGF主要参与促性腺激素分泌过程.Y染色体不存在显著差异表达基因.结论 克氏综合征患者不仅多余X染色体基因差异表达,还有大量常染色体基因差异表达,这可能是克氏综合征临床表型多样化的原因.Objective In our study, we measured RNA expression level in peripheral blood of Klinefeher＇ s syndrome patients and normal males to investigate the relationship between gene differential expression and the clinical phenotype of Klinefelter＇ s syndrome. Methods. In the present study, total mRNA from seven Klinefeher＇ s syndrome patients and seven normal males were analyzed by RNA-sequencing techniques, differentially expressed genes （DEGs） were partially validated by quantitative reverse transcription PCR （ qRT-PCR）. Results Based on the filter thresholds of FDR ≤0.001 and I log2 Ratio ≥11 , 216 differentially expression genes （ DEGs ） in Klinefeher＇ s syndrome group were detected compared with normal male controls, the difference is statistically significant. There were 9 X chromosome genes （4 % ） in the DEGs. And among them, XIST, a major regulator of the X-chromosome inactivation process; was the most significantly over-expressed gene, the remaining 207 DEGs were autosomal genes （96%）. The expression of NR 4 A 3. ZKSCAN 4 、 HBEGF . EREG . AREG 、 NR 4 A 2 、CCR 5 show the significant difference. NR4A3 is associated with the type 2 diabetes, HBEGF is mainly involved in gonadotropin secretion process, and no DGE identified from the Y chromosome. Conclusion In addition to the genes on the extra X chromosome, lots of autosomal genes were differentially expressed in Klinefeher＇ s syndrome patients,our findings may explain the reason for the clinical phenotype diversity of Klinefelter＇ s syndrome patients.

关 键 词：克氏综合征 表达谱 RNA-SEQ 

分 类 号：R596.1[医药卫生—内科学]