Afshari Natalie A, Li Yi-Ju, Pericak-Vance Margaret A, Gregory Simon, Klintworth Gordon K
Duke University Eye Center and the.
Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1093-7. doi: 10.1167/iovs.08-1839. Epub 2008 May 23.
To perform a genome-wide linkage screen with a single-nucleotide polymorphism (SNP) linkage panel to identify regions of genetic linkage in Fuchs endothelial corneal dystrophy (FECD) and to analyze affected individuals for mutations in the COL8A2 gene.
Ninety-two individuals from 22 families with FECD were identified from our multiplex FECD family cohort. A genome-wide linkage scan was performed using an SNP linkage panel. Parametric two-point linkage analyses were calculated and nonparametric multipoint linkage analyses were performed on chromosomes with two-point LOD scores (HLOD) > 1.0. All affected individuals were analyzed for the two previously reported FECD mutations in the COL8A2 gene (L450W and Q455K).
The genome-wide analysis identified five regions with linkage signals from all analyses on chromosomes 1, 7, 15, 17, and X. The highest two-point HLODs were found on the long arm of chromosome 15 with an HLOD of 3.26 for the recessive model and 2.48 for the dominant model. Multipoint linkage analysis also identified a linkage peak on the long arm of chromosome 15 with a LOD > 1. The region of linkage on chromosome 1p, driven by two multigenerational FECD families with a two-point LOD > 2, was adjacent to the previously identified COL8A2 gene; however, the two reported mutations in COL8A2 were not identified in any of the 56 affected individuals in the 92 samples tested.
Genome-wide linkage analysis was used to identify potential linkage regions on chromosomes 1, 7, 15, 17, and X for FECD. The previously reported mutations in the COL8A2 gene were not found in the 92 samples tested.
使用单核苷酸多态性（SNP）连锁分析板进行全基因组连锁筛查，以确定富克斯角膜内皮营养不良（FECD）的遗传连锁区域，并分析受累个体的COL8A2基因突变情况。
从我们的多重FECD家系队列中鉴定出22个FECD家系的92名个体。使用SNP连锁分析板进行全基因组连锁扫描。计算参数化两点连锁分析，并对两点对数优势分数（HLOD）>1.0的染色体进行非参数多点连锁分析。对所有受累个体分析COL8A2基因中两个先前报道的FECD突变（L450W和Q455K）。
全基因组分析在1号、7号、15号、17号和X染色体上的所有分析中均鉴定出五个具有连锁信号的区域。在15号染色体长臂上发现最高的两点HLOD，隐性模型的HLOD为3.26，显性模型的HLOD为2.48。多点连锁分析也在15号染色体长臂上鉴定出一个LOD>1的连锁峰。由两个两点LOD>2的多代FECD家系驱动的1号染色体上的连锁区域与先前鉴定的COL8A2基因相邻；然而，在所检测的92个样本中的56名受累个体中均未鉴定出COL8A2基因中报道的两个突变。
全基因组连锁分析用于鉴定FECD在1号、7号、15号、17号和X染色体上的潜在连锁区域。在所检测的92个样本中未发现COL8A2基因先前报道的突变。
