Genome-wide scan for myopia in the Old Order Amish.
Genome-wide scan for myopia in the Old Order Amish.
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DOI：
10.1016/j.ajo.2005.04.014
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发表时间：
2005-09
影响因子：
4.2
通讯作者：
D. Stambolian;E. Ciner;Lauren Reider;Chris Moy;Debra Dana;R. Owens;Melissa Schlifka;Taura N. Holmes;G. Ibay;J. Bailey-Wilson
中科院分区：
文献类型：
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作者：
D. Stambolian;E. Ciner;Lauren Reider;Chris Moy;Debra Dana;R. Owens;Melissa Schlifka;Taura N. Holmes;G. Ibay;J. Bailey-Wilson
目的在34个Old Order Amish家族（遗传定义明确的创始人群）中确定影响常见近视的近视易感基因。设计一项对至少两名近视患者组成的近视家庭的前瞻性研究。方法确定至少有两个兄弟姐妹患有近视的大家庭。遗传疾病研究中心（CIDR）使用387个标记进行了全基因组连锁扫描。连锁分析采用参数（常染色体显性，固定外显率模型）和非参数方法进行。还进行了无模型连锁分析，以最大限度地提高外显率和显性（即，拟合广泛的显性和隐性模型）。结果在固定外显率模型下，D20S451的最大两点异质性LOD评分（HLOD）为1.59，D6S1021的最大多点异质性LOD评分为1.92。D3S2427处的非参数最大值多点（NPL）的p值为0.0005。在无模型分析中，8号染色体（D8S1130和D8S1106之间的隐性模型）和X号染色体（DXS6800和DXS6789之间的隐性模型）的多点异质性LOD评分均为2.03。使用最佳外显子模型对染色体3、6、8、20和X进行重新分析，结果显示，D3S3053位点的多点hlod最大值为1.84；1.84 at D3S2427；2.04 at D8S1130；和2.34在DXS6800。结论8p23染色体上的位点独立证实了Hammond等人在该区域定位近视数量性状位点（QTL）的报道。
PURPOSETo identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well-defined founder population.DESIGNA prospective study of families with myopia consisting of a minimum of two individuals affected with myopia.METHODSExtended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research (CIDR). Linkage analyses were conducted with parametric (autosomal dominant, fixed penetrance model) and nonparametric methods. Model-free linkage analysis was also performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models).RESULTSUnder the fixed penetrance model, the maximum two-point heterogeneity LOD score (HLOD) was 1.59 at D20S451 and the maximum multipoint HLOD was 1.92 at D6S1021. The nonparametric maximum multipoint (NPL) at D3S2427 had a P-value of .0005. Under the model-free analysis, multipoint heterogeneity LOD scores of 2.03 were observed on both chromosomes 8 (under a recessive model between D8S1130 and D8S1106) and X (under a recessive model between DXS6800 and DXS6789). Reanalyses of chromosomes 3, 6, 8, 20, and X using the best penetrance models resulted in maximum multipoint HLODs of 1.84 at D3S3053; 1.84 at D3S2427; 2.04 at D8S1130; and 2.34 at DXS6800.CONCLUSIONSThe locus on chromosome 8p23 independently confirms a report by Hammond and associates mapping a myopia quantitative trait loci (QTL) to this region.