Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.
Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.
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DOI：
10.1167/iovs.16-21271
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发表时间：
2017-07-01
影响因子：
4.4
通讯作者：
Bailey-Wilson JE
中科院分区：
文献类型：
--
作者：
Musolf AM;Simpson CL;Moiz BA;Long KA;Portas L;Murgia F;Ciner EB;Stambolian D;Bailey-Wilson JE
近视是一种常见的视力障碍，由眼睛过度生长引起，导致视力模糊。它影响了四分之一的美国人，并且其患病率正在增加。近视的遗传机制尚不完全清楚。在这里，我们使用基因型数据和连锁分析来识别与近视显着相关的高风险遗传位点。来自 56 个有近视史的白人家庭的个体在基于外显子组的芯片上进行了基因分型，并将单核苷酸多态性 (SNP) 数据与微卫星基因型数据合并。样本的屈光不正测量结果被转换为二元表型，包括受影响、未受影响或未知的近视状态。参数连锁分析假设常染色体显性模型具有 90% 外显率和 10% 表型率。单变异两点分析在 11p14.1 和 11p11.2 处产生了三个显着连锁的 SNP； 11p 时另外 45 个 SNP 被发现具有暗示性。没有其他染色体具有任何显着的 SNP 或超过 7 个暗示性连锁。其中两个重要的 SNP 位于 BBOX1-AS1 中，一个位于 ORA47 和 TRIM49B 之间的基因间区域。折叠单倍型模式两点分析和多点分析也在 11p 处产生了多个暗示性连锁基因。多点分析还发现了 20q13 上连锁的暗示性证据。我们在 11p 上发现了三个与白种人近视有关的全基因组显着连锁变异。尽管新的特异性信号仍需要复制，但 11p 是一个有前途的区域，已通过其他连锁研究与许多潜在有趣的候选基因一起鉴定。我们希望将 11p 上的这些区域确定为近视的潜在致病区域将导致更多地关注这些区域，并可能在其他研究中复制我们的特定连锁峰。我们进一步计划对连锁程度最高的家族进行 11p 的靶向测序，以更清楚地了解该区域连锁的来源。
Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
9.8
作者：
Hammond, CJ;Andrew, T;Spector, TD
通讯作者：
Spector, TD
影响因子：
4.4
作者：
Klein, Alison P.;Duggal, Priya;Klein, Barbara E. K.
通讯作者：
Klein, Barbara E. K.
DOI：
10.1002/ajmg.1566.abs
发表时间：
2001-11-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Mandal, DM;Wilson, AF;Bailey-Wilson, JE
通讯作者：
Bailey-Wilson, JE
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR