Lesko J G, Lewis R A, Nussbaum R L
Am J Hum Genet. 1987 Apr;40(4):303-11.
Choroideremia (McK30310), an X-linked retinal dystrophy, causes progressive night blindness, visual field constriction, and eventual central blindness in affected males by the third to fourth decade of life. The biochemical basis of the disease is unknown, and prenatal diagnosis is not available. Subregional localization of the choroideremia locus to Xq13-22 was accomplished initially by linkage to two restriction-fragment-length polymorphisms (RFLPs), DXYS1 (Xq13-q21.1) and DXS3 (Xq21.3-22). We have now extended our linkage analysis to 12 families using nine RFLP markers between Xp11.3 and Xq26. Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22. The families were also used to measure recombination frequencies between RFLP loci to provide parameters for the program LINKMAP. Multipoint analysis with LINKMAP provided overwhelming evidence for placing the choroideremia locus within the region bounded by DXS1 (Xq11-13) and DXS17 (Xq21.3-q22). At a finer level of resolution, multipoint analysis suggested that the choroideremia locus was proximal to DXS3 (384:1 odds) rather than distal to it. Data were insufficient, however, to distinguish between a gene order that puts choroideremia between DXS3 and DXYS1 and one that places choroideremia proximal to both RFLP loci. These results provide linkage mapping of choroideremia and RFLP loci in this region that will be of use for further genetic studies as well as for clinical applications in this and other human diseases.
无脉络膜症（McK30310）是一种X连锁视网膜营养不良症，会导致患病男性在30到40岁时逐渐出现夜盲、视野缩小，最终导致中心性失明。该病的生化基础尚不清楚，目前也无法进行产前诊断。最初通过与两个限制性片段长度多态性（RFLP）标记DXYS1（Xq13 - q21.1）和DXS3（Xq21.3 - 22）连锁，将无脉络膜症基因座亚区域定位到Xq13 - 22。我们现在已将连锁分析扩展到12个家系，使用了位于Xp11.3和Xq26之间的9个RFLP标记。在无脉络膜症与位于Xq13 - 22的5个标记（PGK、DXS3、DXYS12、DXS72和DXYS1）之间发现重组频率为0% - 4%。这些家系还用于测量RFLP基因座之间的重组频率，为LINKMAP程序提供参数。使用LINKMAP进行的多点分析提供了压倒性证据，表明无脉络膜症基因座位于由DXS1（Xq11 - 13）和DXS17（Xq21.3 - q22）界定的区域内。在更高分辨率水平上，多点分析表明无脉络膜症基因座位于DXS3近端（优势比为384:1）而非远端。然而，数据不足以区分使无脉络膜症位于DXS3和DXYS1之间的基因顺序与使无脉络膜症位于两个RFLP基因座近端的基因顺序。这些结果提供了该区域无脉络膜症和RFLP基因座的连锁图谱，将用于进一步的遗传学研究以及该疾病和其他人类疾病的临床应用。
