Stambolian Dwight, Ciner Elise B, Reider Lauren C, Moy Chris, Dana Debra, Owens Robert, Schlifka Melissa, Holmes Taura, Ibay Grace, Bailey-Wilson Joan E
Department of Ophthalmology, Stellar Chance Laboratories Rm. 313, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Am J Ophthalmol. 2005 Sep;140(3):469-76. doi: 10.1016/j.ajo.2005.04.014.
To identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well-defined founder population.
A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia.
Extended 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).
Under 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.
The locus on chromosome 8p23 independently confirms a report by Hammond and associates mapping a myopia quantitative trait loci (QTL) to this region.
在34个旧秩序阿米什人家庭（一个基因定义明确的创始人群体）中鉴定影响常见近视的近视易感基因。
对至少有两名近视患者的近视家庭进行前瞻性研究。
确定至少有两名患近视的兄弟姐妹的大家庭。遗传性疾病研究中心（CIDR）使用387个标记进行全基因组连锁扫描。采用参数法（常染色体显性，固定外显率模型）和非参数法进行连锁分析。还进行了无模型连锁分析，使外显率和显性最大化（即拟合广泛的显性和隐性模型）。
在固定外显率模型下，D20S451处的最大两点异质性LOD分数（HLOD）为1.59，D6S1021处的最大多点HLOD为1.92。D3S2427处的非参数最大多点（NPL）的P值为0.0005。在无模型分析中，在8号染色体（在D8S1130和D8S1106之间的隐性模型下）和X染色体（在DXS6800和DXS6789之间的隐性模型下）上均观察到多点异质性LOD分数为2.03。使用最佳外显率模型对3号、6号、8号、20号和X染色体进行重新分析，结果显示D3S3053处的最大多点HLOD为1.84；D3S2427处为1.84；D8S1130处为2.04；DXS6800处为2.34。
8号染色体p23位点独立证实了哈蒙德及其同事的一份报告，该报告将一个近视数量性状位点（QTL）定位到该区域。
