The endless quest for sex determination genes

  title={The endless quest for sex determination genes},
  author={Alice Fleming and Eric Vilain},
  journal={Clinical Genetics},
Disorders in human sex determination cause defects in gonadal function and can result in a spectrum of abnormalities in the internal and external genitalia, ranging from relatively mild sexual ambiguities to complete sex reversal. Several genes involved in sex determination have been validated in humans, and activities of their gene products are being elucidated, particularly in mouse models. However, how these genes interact in an overall process remains far from clear, and it is probable that… 
[Genetic background of sex determination and gonadal development disorders].
  • R. Piprek
  • Biology, Medicine
    Endokrynologia Polska
  • 2008
Comparing data in humans and mice is compared, revealing the existence of many sex-determining genes in both, which should be taken into consideration during the diagnosis of intersexual disorders.
Genetics of Ovarian Differentiation: Rspo1, a Major Player
By generating the corresponding mouse model, it is shown that Rspo1 is so far the earliest known gene controlling the female genetic developmental program and activates the canonical β-catenin signaling pathway required for female somatic cell differentiation and germ cell commitment into meiosis.
DAX1 a sex determining gene in fish
The European sea bass is worked with, which is a fish species that lack heterogametic sex chromosomes, but posess a sex determining mechanism that is strongly influenced by temperature (TSD), and the isolation of the full length sequence and gene structure of DAX1 in the European seabass (sbDAX1).
Loss of Fgfr2 leads to partial XY sex reversal.
Molecular Studies in Horses with SRY-Positive XY Sex Reversal
Investigation of five horses affected with SRY-positive XY sex reversal syndrome found Sequencing of the coding exon region of the SRY gene showed 99-100% alignment with the sequences of normal males, and two statistically significant SNPs were identified in a ~16 Mb region on the long arm of horse chromosome 3 (ECA3q).
Genetic mechanisms underlying male sex determination in mammals
Surprisingly, splicing, nuclear transport, and extramatrix proteins may be involved in sex determination.


ATRX and sex differentiation
Turning on the male – SRY, SOX9 and sex determination in mammals
The current knowledge of SRY and SOX9 structure and function is described and one has proven of central importance to mammals and vertebrates,SOX9.
Mammalian sex determination: from gonads to brain.
A regulatory cascade hypothesis for mammalian sex determination, proposing that SRY represses a negative regulator of male development, was recently supported by observation of mice that expressed a DAX1 transgene and developed as XY sex-reversed females.
Dax1 antagonizes Sry action in mammalian sex determination
Results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.
The genetic basis of murine and human sex determination: a review
Breeding the Y chromosome from certain Mus musculus domesticus strains into the laboratory mouse strain C57BL/6J results in XY male-to-female sex reversal, which suggests both allelic variation of the Sry gene and the presence of autosomal sex determining genes.
Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds
It is found that Sox9 expression closely follows differentiation of Sertoli cells in the mouse testis, in experimental sex reversal when fetal ovaries are grafted to adult kidneys and in the chick where there is no evidence for a Sry gene.
A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779.
Conventional and molecular cytogenetic analyses of metaphase chromosomes from each patient suggest that the smallest region of overlap (SRO) of deletions involves a very small region of distal band 9p24, significantly narrow the putative sex-determining gene to the very terminal region of the short arm of chromosome 9.
Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene
Cloning of a translocation chromosome breakpoint from a sex-reversed patient with campomelic dysplasia, followed by mutation analysis of an adjacent gene, indicates that SOX9, an SRY-related gene, is involved in both bone formation and control of testis development.
Autosomal XX sex reversal caused by duplication of SOX9.
It is suggested that extra dose of SOX9 is sufficient to initiate testis differentiation in the absence of SRY, and other SRY-negative XX sex-reversed individuals deserve thorough investigation of SoX9 gene.
A 11.7-kb deletion triggers intersexuality and polledness in goats
It is demonstrated that the mutation underlying polled intersex syndrome is the deletion of a critical 11.7-kb DNA element containing mainly repetitive sequences, which affects the transcription of at least two genes: PISRT1, encoding a 1.5-kb mRNA devoid of open reading frame (ORF), and FOXL2, recently shown to be responsible for blepharophimosis ptosis epicanthus inversus syndrome (BPES) in humans.