Hawkins J R, Taylor A, Berta P, Levilliers J, Van der Auwera B, Goodfellow P N
Imperial Cancer Research Fund, London, UK.
Hum Genet. 1992 Feb;88(4):471-4. doi: 10.1007/BF00215684.
XY females (n = 17) were analysed for mutations in SRY (sex-determining region Y gene), a gene that has recently been equated with the testis determining factor (TDF). SRY sequences were amplified by the polymerase chain reaction (PCR) and analysed by both the single strand conformational polymorphism assay (SSCP) and DNA sequencing. The DNA from two individuals gave altered SSCP patterns; only these two individuals showed any DNA sequence variation. In both cases, a single base change was found, one altering a tryptophan codon to a stop codon, the other causing a glycine to arginine amino acid substitution. These substitutions lie in the high mobility group (HMG)-related box of the SRY protein, a potential DNA-binding domain. The corresponding regions of DNA from the father of one individual and the paternal uncle of the other, were sequenced and found to be normal. Thus, in both cases, sex reversal is associated with de novo mutations in SRY. Combining this data with two previously published reports, a total of 40 XY females have now been analysed for mutations in SRY. The number of de novo mutations in SRY is now doubled to four, adding further strength to the argument that SRY is TDF.
对17名XY女性进行了分析，以检测SRY（性别决定区Y基因）的突变情况，该基因最近被认为等同于睾丸决定因子（TDF）。通过聚合酶链反应（PCR）扩增SRY序列，并采用单链构象多态性分析（SSCP）和DNA测序进行分析。两名个体的DNA呈现出改变的SSCP模式；只有这两名个体显示出任何DNA序列变异。在这两种情况下，均发现了单个碱基变化，一个将色氨酸密码子改变为终止密码子，另一个导致甘氨酸到精氨酸的氨基酸替换。这些替换位于SRY蛋白的高迁移率族（HMG）相关盒中，这是一个潜在的DNA结合结构域。对其中一名个体的父亲和另一名个体的叔祖父的相应DNA区域进行测序，发现是正常的。因此，在这两种情况下，性反转都与SRY的新发突变有关。将这些数据与之前发表的两篇报告相结合，现在总共对40名XY女性进行了SRY突变分析。SRY的新发突变数量现已翻倍至4个，进一步支持了SRY就是TDF这一观点。
