McKay J D, Patterson B, Craig J E, Russell-Eggitt I M, Wirth M G, Burdon K P, Hewitt A W, Cohn A C, Kerdraon Y, Mackey D A
Genome analysis team, International Agency for Research on Cancer, Lyons, France.
Br J Ophthalmol. 2005 Jul;89(7):831-4. doi: 10.1136/bjo.2004.058495.
Multiple genetic causes of congenital cataract have been identified, both as a component of syndromes and in families that present with isolated congenital cataract. Linkage analysis was used to map the genetic locus in a six generation Australian family presenting with total congenital cataract.
Microsatellite markers located across all known autosomal dominant congenital cataract loci were genotyped in all recruited family members of the Tasmanian family. Both two point and multipoint linkage analysis were used to assess each locus under an autosomal dominant model.
Significant linkage was detected at the telomere of the p arm of chromosome 1, with a maximum two point LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an estimated location score of 5.61 at marker D1S507. Haplotype analysis places the gene inside a critical region between D1S228 and D1S199, a distance of approximately 6 megabases. The candidate gene PAX7 residing within the critical interval was excluded by direct sequencing in affected individuals.
This is the third report of congenital cataract linkage to 1ptel. The critical region as defined by the shared haplotype in this family is clearly centromeric from the Volkmann cataract locus identified through study of a Danish family, indicating that two genes causing autosomal dominant congenital cataract map to the telomeric region of chromosome 1p.
已确定先天性白内障有多种遗传病因，既作为综合征的一部分，也存在于表现为孤立性先天性白内障的家族中。连锁分析被用于在一个患有完全先天性白内障的六代澳大利亚家族中定位遗传位点。
在塔斯马尼亚家族所有招募的家庭成员中，对位于所有已知常染色体显性先天性白内障位点的微卫星标记进行基因分型。采用两点和多点连锁分析在常染色体显性模型下评估每个位点。
在1号染色体p臂的端粒处检测到显著连锁，标记D1S507的最大两点对数优势（LOD）为4.21，最大多点精确LOD为5.44，标记D1S507处的估计定位分数为5.61。单倍型分析将该基因定位在D1S228和D1S199之间的关键区域内，距离约为6兆碱基。通过对受影响个体进行直接测序，排除了位于关键区间内的候选基因PAX7。
这是先天性白内障与1p端粒连锁的第三份报告。该家族共享单倍型所定义的关键区域明显位于通过对一个丹麦家族研究确定的福尔克曼白内障位点的着丝粒侧，表明两个导致常染色体显性先天性白内障的基因定位于1号染色体p臂的端粒区域。
