在一个澳大利亚家族中确认成年发病的原发性开角型青光眼基因座GLC1B位于2cen-q13。

Confirmation of the adult-onset primary open angle glaucoma locus GLC1B at 2cen-q13 in an Australian family.

作者信息

Charlesworth Jac C, Stankovich James M, Mackey David A, Craig Jamie E, Haybittel Michael, Westmore Rodney N, Sale Michèle M

机构信息

Menzies Research Institute, Hobart, Tasmania, Australia.

出版信息

Ophthalmologica. 2006;220(1):23-30. doi: 10.1159/000089271.

DOI:10.1159/000089271

PMID:16374045

Abstract

Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin (MYOC) and optineurin (OPTN) identified at 2 of the loci. Using penetrance-model-free methods, we screened the POAG loci GLC1A-F in an extended Australian pedigree, using 3-5 markers within each locus. p values of less than 0.05 were obtained empirically using SimWalk2 and exactly using Genehunter for 2 markers within the GLC1B region on chromosome 2. Fine mapping of this region produced p values of 0.01 or less at 5 markers flanked by D2S1897 and D2S2269. The 9 cM haplotype of interest overlaps the original GLC1B region. These results provide supportive evidence for the GLC1B locus on chromosome 2cen-q13 and verify the existence of POAG susceptibility gene in this region, increasing the likelihood of gene identification.

摘要

原发性开角型青光眼（POAG）具有遗传异质性，已定位了6个命名的POAG基因座GLC1A - F，并在其中2个基因座上鉴定出了肌纤蛋白（MYOC）和视紫质（OPTN）基因。我们采用无外显率模型的方法，在一个澳大利亚扩展家系中对POAG基因座GLC1A - F进行筛查，每个基因座使用3至5个标记。使用SimWalk2通过经验法获得p值小于0.05，对于2号染色体上GLC1B区域内的2个标记，使用Genehunter精确计算p值。对该区域进行精细定位，在D2S1897和D2S2269侧翼的5个标记处产生了0.01或更小的p值。感兴趣的9厘摩单倍型与原始GLC1B区域重叠。这些结果为2号染色体cen - q13上的GLC1B基因座提供了支持性证据，并证实了该区域存在POAG易感基因，增加了基因鉴定的可能性。