An international collaborative family-based whole-genome linkage scan for high-grade myopia.
An international collaborative family-based whole-genome linkage scan for high-grade myopia.
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DOI：
10.1167/iovs.08-2781
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发表时间：
2009-07
影响因子：
4.4
通讯作者：
Young TL
中科院分区：
文献类型：
--
作者：
Li YJ;Guggenheim JA;Bulusu A;Metlapally R;Abbott D;Malecaze F;Calvas P;Rosenberg T;Paget S;Creer RC;Kirov G;Owen MJ;Zhao B;White T;Mackey DA;Young TL
几个非综合征性高度近视位点主要通过微卫星标记和有限数量的家系进行定位。在这项研究中，全基因组连锁扫描进行了高度近视，使用单核苷酸多态性（SNP）在254个家庭从5个独立的网站。对来自1411名受试者的基因组DNA样品进行基因分型（连锁组IVb; Illumina，San Diego，CA）。对来自10个亚洲人、12个非洲裔美国人和221个高加索人家庭的1201个样本进行连锁分析，在排除质量控制后筛选5744个SNP。分析了两种疾病状态，分别由球面（SPH）和球面等效（SE;球面+柱面/2）定义。使用FASTLINK、HOMOG和MERLIN程序进行参数和非参数两点和多点连锁分析。检查了多个分层数据集，包括总体、中心特异性和人种特异性。如果连锁区域的峰值LOD评分≥ 1.5，则将其视为提示性连锁区域。复制MYP 1、MYP 3、MYP 6、MYP 11、MYP 12和MYP 14基因座。鉴定了9号染色体上的新区域q34.11（rs 913275处的最大NPL= 2.07）。12号染色体区域q21.2-24.12（36.59 cM，MYP 3基因座）在SPH的总体数据集中rs337663处显示出显著的连锁（峰值HLOD = 3.48），并且也被杜克、亚洲人和高加索人子集检测到。潜在的共享区间是种族依赖性的，9.4-cM区域（rs 163016-rs 1520724）由亚洲亚群驱动，1343-cM区域（rs 163016-rs 1520724）由高加索亚群驱动。本研究是迄今为止对家族性高度近视进行的最大规模的连锁扫描。这些结果将有助于识别与近视屈光不正发展和眼生长有关的基因。
Several nonsyndromic high-grade myopia loci have been mapped primarily by microsatellite markers and a limited number of pedigrees. In this study, whole-genome linkage scans were performed for high-grade myopia, using single nucleotide polymorphisms (SNPs) in 254 families from five independent sites. Genomic DNA samples from 1411 subjects were genotyped (Linkage Panel IVb; Illumina, San Diego, CA). Linkage analyses were performed on 1201 samples from 10 Asian, 12 African-American, and 221 Caucasian families, screening for 5744 SNPs after quality-control exclusions. Two disease states defined by sphere (SPH) and spherical equivalence (SE; sphere+cylinder/2) were analyzed. Parametric and nonparametric two-point and multipoint linkage analyses were performed using the FASTLINK, HOMOG, and MERLIN programs. Multiple stratified datasets were examined, including overall, center-specific, and race-specific. Linkage regions were declared suggestive if they had a peak LOD score ≥ 1.5. The MYP1, MYP3, MYP6, MYP11, MYP12, and MYP14 loci were replicated. The novel region q34.11 on chromosome 9 (max NPL= 2.07 at rs913275) was identified. Chromosome 12, region q21.2-24.12 (36.59 cM, MYP3 locus) showed significant linkage (peak HLOD = 3.48) at rs337663 in the overall dataset by SPH and was detected by the Duke, Asian, and Caucasian subsets as well. Potential shared interval was race dependent—a 9.4-cM region (rs163016–rs1520724) driven by the Asian subset and a 1343-cM region (rs163016–rs1520724) driven by the Caucasian subset. The present study is the largest linkage scan to date for familial high-grade myopia. The outcomes will facilitate the identification of genes implicated in myopic refractive error development and ocular growth.
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影响因子：
9.8
作者：
Hammond, CJ;Andrew, T;Spector, TD
通讯作者：
Spector, TD
影响因子：
4.1
作者：
GHAFOUR, IM;ALLAN, D;FOULDS, WS
通讯作者：
FOULDS, WS
影响因子：
4.4
作者：
Lam, Ching Yan;Tam, Pancy O. S.;Lam, Dennis S. C.
通讯作者：
Lam, Dennis S. C.
影响因子：
4.4
作者：
Farbrother, JE;Kirov, G;Guggenheim, JA
通讯作者：
Guggenheim, JA
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR