Berta P, Hawkins J R, Sinclair A H, Taylor A, Griffiths B L, Goodfellow P N, Fellous M
Human Molecular Genetics, Imperial Cancer Research Fund, London, UK.
Nature. 1990 Nov 29;348(6300):448-50. doi: 10.1038/348448A0.
The testis-determining factor gene (TDF) lies on the Y chromosome and is responsible for initiating male sex determination. SRY is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for TDF. Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes or by other deletions. If SRY is TDF, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in SRY. We have tested human XY females and normal XY males for alterations in SRY using the single-strand conformation polymorphism assay and subsequent DNA sequencing. A de novo mutation was found in the SRY gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the SRY gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that SRY is required for male sex determination.
睾丸决定因子基因（TDF）位于Y染色体上，负责启动男性性别决定。SRY是位于人类和小鼠Y染色体性别决定区域的一个基因，具有TDF所预期的许多特性。XY女性的性反转是由于睾丸决定或分化途径的失败所致。一些患有性腺发育不全的XY女性，通过性染色体之间的末端交换或其他缺失，从Y染色体上丢失了性别决定区域。如果SRY是TDF，那么可以预测，一些没有Y染色体缺失的性反转XY女性，其SRY基因会发生突变。我们使用单链构象多态性分析及随后的DNA测序，检测了人类XY女性和正常XY男性的SRY基因改变。在一名XY女性的SRY基因中发现了一个新生突变：该突变在患者正常的父亲和兄弟中不存在。在另一名XY女性的SRY基因中发现了另一个变异，但在这种情况下，正常的父亲也有相同的改变。第二种情况中的变异可能偶然与性反转相关，或易导致性反转；与性反转相关的新生突变提供了令人信服的证据，表明SRY是男性性别决定所必需的。
