A genome-wide scan for primary open-angle glaucoma (POAG):: the Barbados Family Study of Open-Angle Glaucoma
A genome-wide scan for primary open-angle glaucoma (POAG):: the Barbados Family Study of Open-Angle Glaucoma
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DOI：
10.1007/s00439-003-0910-z
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发表时间：
2003-05-01
期刊：
影响因子：
5.3
通讯作者：
Hejtmancik, F
中科院分区：
文献类型：
--
作者：
Nemesure, B;Jiao, XD;Hejtmancik, F
原发性开角型青光眼（POAG）的特征是视神经损伤伴视力丧失。通过对大多数白种人家族的遗传连锁分析，已确定了6个命名的遗传位点与POAG易感性有关，并确定了6个致病基因中的2个。巴巴多斯开角型青光眼家族研究（BFSG）旨在评估非洲裔人群中POAG的遗传成分。对来自西印度群岛巴巴多斯146个家庭的1327名个体进行了全基因组扫描。连锁结果的基础上，模型和参数估计来自这些家庭的分离分析，和无模型分析。在染色体1、2、9、10、11和14上鉴定出两点LOD评分>1.0，在染色体2、10和14上发现多点LOD评分增加。随后进行了精细定位，并表明POAG可能与染色体2 q上D2 S2188和D2 S2178之间的间隔以及染色体10 p上D10 S1477和D10 S601之间的间隔连锁。异源性检测强烈支持青光眼与这些区域中的至少一个区域的联系，并提示可能与两者都有联系。虽然TIGR/myocilin和optineurin突变已被证明与其他人群中的POAG有因果关系，但本研究的结果不支持这些基因中的任何一个作为已知POAG发病率相对较高的非洲-加勒比人群的致病基因。
Primary open-angle glaucoma (POAG) is characterized by damage to the optic nerve with associated loss of vision. Six named genetic loci have been identified as contributing to POAG susceptibility by genetic linkage analysis of mostly Caucasian families, and two of the six causative genes have been identified. The Barbados Family Study of Open-Angle Glaucoma (BFSG) was designed to evaluate the genetic component of POAG in a population of African descent. A genome-wide scan was performed on 1327 individuals from 146 families in Barbados, West Indies. Linkage results were based on models and parameter estimates derived from a segregation analysis of these families, and on model-free analyses. Two-point LOD scores >1.0 were identified on chromosomes 1, 2, 9, 10, 11, and 14, with increased multipoint LOD scores being found on chromosomes 2, 10, and 14. Fine mapping was subsequently carried out and indicated that POAG may be linked to intervals on chromosome 2q between D2S2188 and D2S2178 and chromosome 10p between D10S1477 and D10S601. Heterogeneity testing strongly supports linkage for glaucoma to at least one of these regions and suggests possible linkages to both. Although TIGR/myocilin and optineurin mutations have been shown to be causally linked to POAG in other populations, findings from this study do not support either of these as causative genes in an Afro-Caribbean population known to have relatively high rates of POAG.