Owczarek C M, Portbury K J, Hardy M P, O'Leary D A, Kudoh J, Shibuya K, Shimizu N, Kola I, Hertzog P J
Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia.
Gene. 2004 Jan 7;324:65-77. doi: 10.1016/j.gene.2003.09.047.
We have carried out a detailed annotation of 550 kb of genomic DNA on human chromosome 21 containing the ERG and ETS2 genes. Comparative genomic analysis between this region and the interval of conserved synteny on mouse chromosome 16 indicated that the order and orientation of the ERG and ETS2 genes were conserved and revealed several regions containing potential conserved noncoding sequences. Four pseudogenes including those for small protein G, laminin receptor, human transposase protein and meningioma-expressed antigen were identified. A potentially novel gene (C21orf24) with alternative mRNA transcripts, consensus splice donor and acceptor sites, but no coding potential nor murine orthologue, was identified and found to be expressed in a range of human cell lines. We have identified four novel splice variants that arise from a previously undescribed 5' exon of the human ERG gene. Comparison of the cDNA sequences enabled us to determine the complete exon-intron structure of the ERG gene. We have also identified the presence of noncoding RNAs in the first and second introns of the ETS2 gene. Our studies have important implications for Down syndrome as this region contains multiple mRNA transcripts, both coding and potentially noncoding, that may play as yet undescribed roles in the pathogenesis of this disorder.
我们对人类21号染色体上包含ERG和ETS2基因的550 kb基因组DNA进行了详细注释。该区域与小鼠16号染色体上保守同线性区间的比较基因组分析表明，ERG和ETS2基因的顺序和方向是保守的，并揭示了几个包含潜在保守非编码序列的区域。鉴定出四个假基因，包括小蛋白G、层粘连蛋白受体、人类转座酶蛋白和脑膜瘤表达抗原的假基因。鉴定出一个潜在的新基因（C21orf24），它具有可变的mRNA转录本、共有剪接供体和受体位点，但没有编码潜力，也没有小鼠直系同源物，并且发现在一系列人类细胞系中表达。我们鉴定出了四种新的剪接变体，它们来自人类ERG基因一个先前未描述的5'外显子。通过比较cDNA序列，我们能够确定ERG基因完整的外显子-内含子结构。我们还在ETS2基因的第一和第二内含子中鉴定出了非编码RNA的存在。我们的研究对唐氏综合征具有重要意义，因为该区域包含多种mRNA转录本，既有编码的，也有潜在非编码的，它们可能在这种疾病的发病机制中发挥尚未描述的作用。
