Malagó Wilson, Sommer César A, Del Cistia Andrade Camillo, Soares-Costa Andrea, Abrao Possik Patricia, Cassago Alexandre, Santejo Silveira Henrique C, Henrique-Silva Flavio
Department of Genetics and Evolution, Federal University of Sao Carlos, Rodovia Washington Luis, Km 235, CEP 13565-905, Sao Carlos, SP, Brazil.
Croat Med J. 2005 Aug;46(4):647-56.
Identification of differences in the gene expression patterns of Down syndrome and normal leukocytes.
We constructed the first Down syndrome leukocyte serial analysis of gene expression (SAGE) library from a 28 year-old patient. This library was analyzed and compared with a normal leukocyte SAGE library using the eSAGE software. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to validate the results.
We found that a large number of unidentified transcripts were overexpressed in Down syndrome leukocytes and some transcripts coding for growth factors (e.g. interleukin 8, IL-8), ribosomaproteins (e.g. L13a, L29, and L37), and transcription factors (e.g., Jun B, Jun D, and C/EBP beta) were underexpressed. The SAGE data were successfully validated for the genes IL-8, CXCR4, BCL2A1, L13a, L29, L37, and GTF3A using RT-PCR.
Our analysis identified significant changes in the expression pattern of Down syndrome leukocytes compared with normal ones, including key regulators of growth and proliferation, ribosomal proteins, and a large number of overexpressed transcripts that were not matched in UniGene clusters and that may represent novel genes related to Down syndrome. This study offers a new insight into transcriptional changes in Down syndrome leukocytes and indicates candidate genes for further investigations into the molecular mechanism of Down syndrome pathology.
鉴定唐氏综合征与正常白细胞基因表达模式的差异。
我们构建了一名28岁患者的首个唐氏综合征白细胞基因表达序列分析（SAGE）文库。使用eSAGE软件对该文库进行分析，并与正常白细胞SAGE文库进行比较。采用逆转录聚合酶链反应（RT-PCR）验证结果。
我们发现大量未鉴定的转录本在唐氏综合征白细胞中过度表达，而一些编码生长因子（如白细胞介素8，IL-8）、核糖体蛋白（如L13a、L29和L37）以及转录因子（如Jun B、Jun D和C/EBPβ）的转录本表达不足。使用RT-PCR成功验证了IL-8、CXCR4、BCL2A1、L13a、L29、L37和GTF3A基因的SAGE数据。
我们的分析确定了唐氏综合征白细胞与正常白细胞相比，其表达模式有显著变化，包括生长和增殖的关键调节因子、核糖体蛋白，以及大量在UniGene簇中未匹配且可能代表与唐氏综合征相关新基因的过度表达转录本。本研究为唐氏综合征白细胞的转录变化提供了新的见解，并指出了用于进一步研究唐氏综合征病理分子机制的候选基因。
