Chen H, Antonarakis S E
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Hum Genet. 1997 Feb;99(2):262-5. doi: 10.1007/s004390050350.
Exon trapping was used to identify portions of human chromosome 21-encoded genes. More than 600 potential exons on the chromosome have been cloned and characterised to date. A BLAST search of databases revealed that three of these trapped "exons", hmc18a08, hmc18f10 and hmc27g09, showed strong homology to different regions of the Drosophila mnb (Genbank X70794) and rat Dyrk (Genbank X79769) genes, indicating that these three exons may be portions of a human homologue of these genes (we termed this gene MNB for minibrain). With amplification by the polymerase chain reaction and hybridisation analysis we have mapped the human MNB gene on overlapping yeast artificial chromosomes 336G11 and 806A11 of chromosome 21q22.2 between markers D21S65 and ERG. The Drosophila mnb (minibrain) gene, which encodes a member of the protein kinase family, is involved in postembryonic neurogenesis. The Dyrk gene, which encodes a dual specificity protein kinase, is a rat homologue of the Drosophila mnb gene. The kinase activity is dependent on tyrosine residues in the catalytic domain, and it has been speculated that the protein is involved in control of the cell cycle. Altered expression of the human MNB gene may be involved in the pathogenesis of certain phenotypes of Down syndrome, including mental retardation.
外显子捕获技术被用于鉴定人类21号染色体编码基因的部分序列。到目前为止,该染色体上600多个潜在外显子已被克隆和表征。对数据库进行BLAST搜索发现,其中三个捕获的“外显子”hmc18a08、hmc18f10和hmc27g09与果蝇mnb(基因库X70794)和大鼠Dyrk(基因库X79769)基因的不同区域具有高度同源性,表明这三个外显子可能是这些基因人类同源物的部分序列(我们将该基因命名为MNB,即小脑症基因)。通过聚合酶链反应扩增和杂交分析,我们已将人类MNB基因定位在21号染色体q22.2区的重叠酵母人工染色体336G11和806A11上,位于标记D21S65和ERG之间。果蝇mnb(小脑症)基因编码蛋白激酶家族的一个成员,参与胚胎后期神经发生。Dyrk基因编码双特异性蛋白激酶,是果蝇mnb基因的大鼠同源物。该激酶活性依赖于催化结构域中的酪氨酸残基,据推测该蛋白参与细胞周期调控。人类MNB基因表达的改变可能与唐氏综合征某些表型的发病机制有关,包括智力迟钝。