【作者】 赵玉霞； 李克秋； 刘沙沙； 何晓波； 景亚青； 李光；

【Author】 Yuxia Zhao~1,Keqiu Li~l,Shasha Liu~2,Xiaobo He~1,Yaqing Jing~1,Guang Li~(1,*) 1 Department of Medical Biology,Basic Medical college,Tianjin Medical University 2 Tianjin Central Hospital of Gynecology Obstetrics + These authors contributed equally to this work Department of Medical Biology,Basic Medical college,Tianjin Medical University,300070,China.

【机构】 天津医科大学基础医学院医用生物学教研室； 天津市中心妇产科医院；

【摘要】 目的:探讨Klinefelter syndrome(KS)基因差异表达与临床表型多样化之间的关系。方法:采用RNA-seq方法对KS患者和正常对照(男、女)全基因组mRNA进行测序,运用RT-PCR验证测序结果。结果:KS与男性对照组比较,显著差异表达基因(DGEs)216个,X染色体9个,其中XIST与TSC22D3差异表达显著,XIST与X染色体失活及乳腺癌有关,TSC22D3对类固醇及趋化因子的免疫抑制起关键作用;常染色体上基因207个,其中NR4A3与2型糖尿病有关,而AREG与精子发生或隐睾症有关;Y染色体无差异表达基因。KS与女性对照组比较,X染色体、常染色体、Y染色体上均有基因差异表达,共243个。结论:不仅KS患者额外X染色体基因表达使患者表型发生改变,同时体内常染色体基因差异表达也可导致患者临床表型多样化现象。更多还原

【Abstract】 Aim:Explore the relationship between gene differential expression and the considerable phenotype variation of Klinefelter syndrome(KS).Method:In the present study,total mRNA in KS patients,normal males and females were analyzed by RNA-sequencing techniques, differentially expressed genes(DEGs) were validated by quantitative reverse transcriptase PCR (qRT-PCR).Result:Compared with the normal male controls,in the KS group,there were 216 differentially DEGs including nine genes in X chromosome.In nine X-linked gene,the changes in the expression of XIST and TSC22D3 were significant.Gene XIST,which produces a long noncoding RNA involved in X-chromosome inactivation.Over-expression of gene XIST represent important factors in tumorgenesis.The protein encoded by gene TSC22D3 appears to play a key role in the anti-inflammatory and immunosuppressive effects of this steroid and chemokine.The remaining 207 DEGs were autosomal genes,the expression of NR4A3 and AREG showed the significant differences.NR4A3 is mainly related to type 2 diabetes.The AREG may affects spermatogenesis and cryptorchidism.No DEGs were found on the Y chromosome.Compared with normal female controls,in KS group,there were 243 DEGs including six X-linked genes,226 autosomal genes,and 11 Y-linked genes.Conclusion:Not only expression changes of X-linked genes can affect the phenotype of the KS,but also some autosomal gene expression are related the varied phenotype in KS patients.更多还原