Ashley C T, Sutcliffe J S, Kunst C B, Leiner H A, Eichler E E, Nelson D L, Warren S T
Howard Hughes Medical Institute, Emory University School of Medicine, Atlanta, Georgia 30322.
Nat Genet. 1993 Jul;4(3):244-51. doi: 10.1038/ng0793-244.
Fragile X syndrome is associated with massive expansion of a CGG trinucleotide repeat within the FMR-1 gene and transcriptional silencing of the gene due to abnormal methylation. Partial cDNA sequence of the human FMR-1 has been reported. We report here the isolation and characterization of cDNA clones encoding the murine homologue, fmr-1, which exhibit marked sequence identity with the human gene, including the conservation of the CGG repeat. A conserved ATG downstream of the CGG repeat in human and mouse and an in-frame stop codon in other human 5' cDNA sequences demarcate the FMR-1 coding region and confine the CGG repeat to the 5' untranslated region. We also present evidence for alternative splicing of the FMR-1 gene in mouse and human brain and show that one of these splicing events alters the FMR-1 reading frame, predicting isoforms with novel carboxy termini.
脆性X综合征与FMR-1基因内CGG三核苷酸重复序列的大量扩增以及由于异常甲基化导致的该基因转录沉默有关。人类FMR-1的部分cDNA序列已有报道。我们在此报告编码小鼠同源物fmr-1的cDNA克隆的分离和特性，其与人类基因具有显著的序列同一性，包括CGG重复序列的保守性。人类和小鼠中CGG重复序列下游保守的ATG以及其他人类5' cDNA序列中的框内终止密码子划定了FMR-1编码区，并将CGG重复序列限制在5'非翻译区。我们还提供了小鼠和人类大脑中FMR-1基因可变剪接的证据，并表明这些剪接事件之一改变了FMR-1阅读框，预测了具有新羧基末端的异构体。
