IDENTIFICATION OF THE GENE(S) RESPONSIBLE FOR ALAGILLE SYNDROME

Alagille综合征是一种影响肝脏的常染色体显性遗传疾病， 心脏，脊椎，眼睛和脸AGS的基因位点已经被定位 到由STS D20 S189和D20 S162在20 p12处定义的1，300 kb间隔。我们 构建了由BAC和PAC组成的细菌克隆重叠群 AGS区域的克隆。我们努力构建一个 这一区域导致了两个转录本的鉴定。基于 在与CpG岛的序列同源性上，大鼠基因的同源物具有 被识别。已分离全长cDNA（6 kb）， 包括约2.5kb的5 ′启动子区。此外，本发明还提供了一种方法， 我们从总共38个定位的EST中鉴定出两个位于AGS区域的EST， 20号染色体上其中一个是一个很好表征的神经元的一部分 特异性基因（SNAP 25）。目前正在努力查明所有 AGS间期的转录本。将使用来自重叠群的克隆 来鉴定亚显微缺失以缩小AGS区域。的 SNAP 25，大鼠基因和所有其他基因的人类同源物 将通过Southern， 北方，SSCP/ddF方法，以确定基因负责 对于AGS。

Alagille syndrome is an autosomal dominant disorder affecting liver, heart, vertebrae, eyes and faces. The locus for the AGS has been mapped to a 1,300 kb interval defined by STSs D20S189 and D20S162 at 20p12. We have constructed a bacterial clone contig consisting of BAC and PAC clones for the AGS region. Our efforts to construct a transcript map of this region have resulted in the identification of two transcripts. Based on the sequence homology to a CpG island, a homologue of a rat gene has been identified. The full length cDNA (6 kb) has been isolated and sequenced including a 5' promoter region of about 2.5 kb. In addition, we identified two ESTs in the AGS region from a total of 38 ESTs mapped to chromosome 20. One of them is part of a well characterized neuron specific gene (SNAP25). Efforts are being made to identify all the transcripts in the AGS interval. The clones from the contig will be used to identify submicroscopic deletions to narrow the AGS region. The SNAP25, the human homolog of the rat gene and all the other genes identified will be subjected to mutational analysis by Southern, Northern, SSCP/ddF methods in order to identify the gene(s) responsible for AGS.