Genetic evidence equating SRY and the testis-determining factor

Abstract

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.

Sex redefined

“…In 1990, researchers made headlines when they uncovered the identity of this gene 3,4 , which they called SRY. Just by itself, this gene can switch the gonad from ovarian to testicular development.…”

Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population

“…The sex-determining region of Y chromosome (SRY) is the PY53.2 section on the Yp, about 2.1 kb, nears the pseudoautosomal region. Sinclair et al discovered the SRY in 1990 and they considered that SRY is the best candidate gene for the TDF [14]. Lots of studies have shown that the proteins encoded by the SRY gene play a crucial role in sex determination and differentiation [15][16][17].…”

Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development

“…The entire open reading frame of the sexdetermining region Y (SRY) gene was amplified and directly sequenced as described (2,3).…”

“…Normal sexual differentiation in 46,XY individuals relies on a complex cascade of numerous genes, many of which have yet to be identified (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Defects in these genes can cause disorders of sexual development of varying severity.…”