Genome-wide detection of alternative splicing in expressed sequences of human genes
Genome-wide detection of alternative splicing in expressed sequences of human genes
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DOI：
10.1093/nar/29.13.2850
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发表时间：
2001-07-01
影响因子：
14.9
通讯作者：
Lee, C
中科院分区：
文献类型：
--
作者：
Modrek, B;Resch, A;Lee, C
通过对表达序列标签（ESTs）进行全基因组分析，我们在人类基因中确定了6201种可变剪接关系。从约210万条人类mRNA和EST序列入手，我们将表达序列映射到人类基因组草图序列上，并且只接受符合标准剪接位点共有序列的剪接。其中很大一部分（47%）被多次观察到，这表明它们在mRNA种类中占相当大的比例。绝大多数检测到的可变形式似乎是新的，并且在已知和新的人类基因中对功能产生高度特异性、具有生物学意义的调控，例如从HLA - DMβ链中特异性去除溶酶体靶向信号，用不同的跨膜结构域和胞质尾替换Fc受体β链同源物中的C末端跨膜结构域和胞质尾，可能调节其信号转导活性。我们的数据表明，很大比例的人类基因，可能是42%或更多，存在可变剪接，但这似乎主要在某些类型的分子（例如细胞表面受体）和系统功能中被观察到，特别是免疫系统和神经系统。这些结果为理解可变剪接在人类基因组中的作用提供了一个全面的数据集，可在http://www.bioinformatics.ucla.edu/HASDB获取。
We have identified 6201 alternative splice relationships in human genes, through a genome-wide analysis of expressed sequence tags (ESTs), Starting with similar to2.1 million human mRNA and EST sequences, we mapped expressed sequences onto the draft human genome sequence and only accepted splices that obeyed the standard splice site consensus. A large fraction (47%) of these were observed multiple times, indicating that they comprise a substantial fraction of the mRNA species. The vast majority of the detected alternative forms appear to be novel, and produce highly specific, biologically meaningful control of function in both known and novel human genes, e.g. specific removal of the lysosomal targeting signal from HLA-DM beta chain, replacement of the C-terminal transmembrane domain and cytoplasmic tail in an FC receptor beta chain homolog with a different transmembrane domain and cytoplasmic tail, likely modulating its signal transduction activity. Our data indicate that a large proportion of human genes, probably 42% or more, are alternatively spliced, but that this appears to be observed mainly in certain types of molecules (e.g. cell surface receptors) and systemic functions, particularly the immune system and nervous system. These results provide a comprehensive dataset for understanding the role of alternative splicing in the human genome, accessible at http://www.bioinformatics.ucla.edu/HASDB.