Gould D B, Walter M A
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
Genomics. 2000 Sep 15;68(3):336-42. doi: 10.1006/geno.2000.6307.
The Bar subclass of homeodomain proteins was first identified for its role in Drosophila eye development. The Bar subclass homolog, Barx1, has since been cloned in mouse and in chick. The expression of Barx1 in developing teeth and craniofacial mesenchyme of neural crest origin makes it a strong candidate for the related human disorders of Axenfeld-Reiger syndrome (ARS) and iridogoniodysgenesis syndrome (IGDS). Here we report the cloning and characterization of a novel human Bar class gene, human BARX1. Screening of a human fetal craniofacial library resulted in the isolation of a 1.6-kb full-length transcript. Sequence analysis indicated that human BARX1, mouse Barx1, and chick Barx1 show 100% identity at the amino acid level within their homeodomains. Human BARX1 is expressed in a number of tissues including testis and heart by Northern analysis and in iris and craniofacial tissues by PCR of cDNA libraries. BARX1 chromosomal localization to 9q12 was determined by radiation hybrid mapping. Intron/exon boundaries were established, and primers were generated to PCR amplify all four exons. A mutation screen was conducted in 55 patients affected with ARS, IGDS, or related ocular malformations. While six sequence polymorphisms were detected, no disease-causing mutations of BARX1 were observed.
同源异型域蛋白的Bar亚类最初因其在果蝇眼睛发育中的作用而被鉴定出来。此后，Bar亚类的同源物Barx1已在小鼠和鸡中克隆出来。Barx1在源自神经嵴的发育中的牙齿和颅面间充质中的表达，使其成为阿克森费尔德-里格尔综合征（ARS）和虹膜房角发育异常综合征（IGDS）相关人类疾病的有力候选基因。在此，我们报告一种新型人类Bar类基因——人类BARX1的克隆和特征。对人类胎儿颅面文库的筛选导致分离出一个1.6 kb的全长转录本。序列分析表明，人类BARX1、小鼠Barx1和鸡Barx1在其同源异型域内的氨基酸水平上显示出100%的同一性。通过Northern分析，人类BARX1在包括睾丸和心脏在内的多种组织中表达，通过cDNA文库的PCR在虹膜和颅面组织中表达。通过辐射杂种图谱确定了BARX1在染色体上定位于9q12。确定了内含子/外显子边界，并生成引物以PCR扩增所有四个外显子。对55名患有ARS、IGDS或相关眼部畸形的患者进行了突变筛查。虽然检测到六个序列多态性，但未观察到BARX1的致病突变。
