Nathans J, Maumenee I H, Zrenner E, Sadowski B, Sharpe L T, Lewis R A, Hansen E, Rosenberg T, Schwartz M, Heckenlively J R
Howard Hughes Medical Institute, Department of Molecular Biology, Baltimore, MD.
Am J Hum Genet. 1993 Nov;53(5):987-1000.
Thirty-three unrelated subjects with blue-cone monochromacy or closely related variants of blue-cone monochromacy were examined for rearrangements in the tandem array of genes encoding the red- and green-cone pigments. In 24 subjects, eight genotypes were found that would be predicted to eliminate the function of all of the genes within the array. As observed in an earlier study, the rearrangements involve either deletion of a locus control region adjacent to the gene array or loss of function via homologous recombination and point mutation. One inactivating mutation, Cys203-to-Arg, was found in 15 probands who carry single genes and in both visual pigment genes in one subject whose array has two genes. This mutation was also found in at least one of the visual pigment genes in 1 subject whose array has multiple genes and in 2 of 321 control subjects, suggesting that preexisting Cys203-to-Arg mutations constitute a reservoir of chromosomes that are predisposed to generate blue-cone-monochromat genotypes by unequal homologous recombination and/or gene conversion. Two other point mutations were identified: (a) Arg247-to-Ter in one subject with a single red-pigment gene and (b) Pro307-to-Leu in one subject with a single 5' red-3' green hybrid gene. The observed heterogeneity of genotypes points to the existence of multiple one- and two-step mutational pathways to blue-cone monochromacy.
对33名患有蓝锥单色视或蓝锥单色视密切相关变体的无关受试者进行了检查，以确定编码红锥和绿锥色素的基因串联阵列中的重排情况。在24名受试者中，发现了8种基因型，预计这些基因型会消除阵列中所有基因的功能。正如早期研究中所观察到的，重排涉及与基因阵列相邻的基因座控制区的缺失，或通过同源重组和点突变导致功能丧失。在15名携带单个基因的先证者以及1名阵列中有两个基因的受试者的两个视色素基因中，均发现了一种失活突变，即Cys203突变为Arg。在1名阵列中有多个基因的受试者的至少一个视色素基因中以及321名对照受试者中的2名中也发现了这种突变，这表明预先存在的Cys203突变为Arg的突变构成了一个染色体库，这些染色体易于通过不等位同源重组和/或基因转换产生蓝锥单色视基因型。还鉴定出另外两个点突变：（a）一名携带单个红色素基因的受试者中Arg247突变为Ter；（b）一名携带单个5'红-3'绿杂交基因的受试者中Pro307突变为Leu。观察到的基因型异质性表明存在多种导致蓝锥单色视的单步和两步突变途径。
