Belmouden A, Adam M F, Dupont de Dinechin S, Brézin A P, Rigault P, Chumakov I, Bach J F, Garchon H J
INSERM U25, Hôpital Necker, 161, Paris, France.
Genomics. 1997 Feb 1;39(3):348-58. doi: 10.1006/geno.1996.4491.
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness in industrialized countries. A locus for juvenile-onset POAG, GLC1A, has been mapped to 1q21-q31 in a 9-cM interval. With recombinant haplotypes, we have now reduced the GLC1A interval to a maximum of 3 cM, between the D1S452/NGA1/D1S210 and NGA5 loci. These loci are 2.8 Mb apart on a 4.7-Mb contig that we have completed between the D1S2851 and D1S218 loci and that includes 96 YAC clones and 48 STSs. The new GLC1A interval itself is now covered by 25 YACs, 30 STSs, and 16 restriction enzyme site landmarks. The lack of a NotI site suggests that the region has few CpG islands and a low gene content. This is compatible with its predominant cytogenetic location on the 1q24 G-band. Finally, we have excluded important candidate genes, including genes coding for three ATPases (ATP1B1, ATP2B4, ATP1A2), an ion channel (VDAC4), antithrombine III (AT3), and prostaglandin synthase (PTGS2). Our results provide a basis to identify the GLC1A gene.
原发性开角型青光眼（POAG）是工业化国家不可逆性失明的主要原因。青少年型POAG的一个基因座GLC1A已被定位到1q21 - q31区间，跨度为9厘摩（cM）。通过重组单倍型，我们现已将GLC1A区间缩小至最大3 cM，位于D1S452/NGA1/D1S210和NGA5基因座之间。这些基因座在我们完成的一个4.7兆碱基（Mb）重叠群上相距2.8 Mb，该重叠群位于D1S2851和D1S218基因座之间，包含96个酵母人工染色体（YAC）克隆和48个序列标签位点（STS）。新的GLC1A区间本身现在由25个YAC、30个STS和16个限制性酶切位点标记覆盖。缺乏NotI位点表明该区域几乎没有CpG岛且基因含量较低。这与其在1q24 G带的主要细胞遗传学定位相符。最后，我们排除了重要的候选基因，包括编码三种ATP酶（ATP1B1、ATP2B4、ATP1A2）、一种离子通道（VDAC4）、抗凝血酶III（AT3）和前列腺素合酶（PTGS2）的基因。我们的结果为鉴定GLC1A基因提供了基础。
