Linkage analysis of the genetic loci for high myopia on 18p, 12q, and 17q in 51 UK families
Linkage analysis of the genetic loci for high myopia on 18p, 12q, and 17q in 51 UK families
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DOI：
10.1167/iovs.03-1156
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Guggenheim, JA
中科院分区：
文献类型：
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作者：
Farbrother, JE;Kirov, G;Guggenheim, JA
目的。旨在确定 51 个英国家庭的高度近视在多大程度上可归因于目前确定的遗传位点。方法。这些家庭由 245 名受试者组成，具有可用的表型信息和 DNA，其中 170 人被归类为受影响者。对受试者进行了微卫星标记的基因分型，这些微卫星标记横跨 18p (MYP2)、12q (MYP3) 和 17q 上类似于 40cM 区域，以及 COL2A1、COL11A1 和 FBN1 侧翼的标记。使用与原始出版物中使用的相同的疾病基因分离模型进行两点连锁分析，然后使用Genehunter（纽约州洛克菲勒大学在公共领域提供的http://linkage.rockefeller.edu/soft/gh/）进行非参数和多点分析，并对参数α（连锁家族的比例）进行额外的最大化。结果。发现 12q 上 MYP3 基因座存在连锁证据（对于标记 D12S332，两点 Z(max) = 2.54，P = 0.0003 和多点 hLOD = 1.08，α = 0.24，P = 0.023；对于标记，非参数连锁 [NPL] = 1.49，P = 0.07 D12S1607）。对于 17q 位点，在隐性模型下存在过多等位基因共享和连锁的微弱证据（对于标记 D17S956，NPL = 1.34，P = 0.09；对于标记 D17S1795，在 alpha = 0.30 时两点 hLOD = 1.24；对于 alpha = 0.17 时的多点 hLOD = 1.24，对于位于 α = 0.17 的标记，P = 0.014 77.68 cM，标记 D17S956 和 D17S1853 之间）。未发现与 18p 上的 MYP2 基因座或与 COL2A1、COL11A1 和 FBN1 基因的显着连锁。结论。这些结果表明，12q 上的 MYP3 基因座可能是大约 25% 的英国家庭高度近视的原因，表现出明显的常染色体显性遗传，但 18p 和 17q 上的基因座不太常见。因此，高度近视的额外位点可能是英国大多数高度近视病例的原因。
PURPOSE. To determine the extent to which high myopia in a cohort of 51 U. K. families can be attributed to currently identified genetic loci.METHODS. The families comprised 245 subjects with phenotypic information and DNA available, of whom 170 were classified as affected. Subjects were genotyped for microsatellite markers spanning similar to40cM regions on 18p (MYP2), 12q (MYP3) and 17q, together with markers flanking COL2A1, COL11A1, and FBN1. Two-point linkage analyses were performed using the same disease gene segregation model as was used in the original publications, followed by nonparametric and multipoint analyses using Genehunter (http://linkage.rockefeller. edu/soft/gh/ provided in the public domain by Rockefeller University, New York, NY), with additional maximization over the parameter alpha, the proportion of linked families.RESULTS. Evidence of linkage was found for the MYP3 locus on 12q (two-point Z(max) = 2.54, P = 0.0003 and multipoint hLOD = 1.08 at alpha = 0.24, P = 0.023 for marker D12S332; nonparametric linkage [NPL] = 1.49, P = 0.07 for marker D12S1607). For the 17q locus there was weak evidence of excess allele sharing and linkage under a recessive model (NPL = 1.34, P = 0.09 for marker D17S956; two-point hLOD = 1.24 at alpha = 0.30 for marker D17S1795; multipoint hLOD = 1.24 at alpha = 0.17, P = 0.014 for marker at 77.68 cM, between markers D17S956 and D17S1853). No significant linkage was found to the MYP2 locus on 18p, or to the COL2A1, COL11A1, and FBN1 genes.CONCLUSIONS. These results suggest that the MYP3 locus on 12q could be responsible for high myopia in approximately 25% of the U.K. families showing apparent autosomal dominant transmission, but that the loci on 18p and 17q are less common causes. Thus, additional loci for high myopia are likely to be the cause of the majority of cases of high myopia in the United Kingdom.