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Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal.

Publication ,  Journal Article
Munger, SC; Aylor, DL; Syed, HA; Magwene, PM; Threadgill, DW; Capel, B
Published in: Genes Dev
November 1, 2009

Despite the identification of some key genes that regulate sex determination, most cases of disorders of sexual development remain unexplained. Evidence suggests that the sexual fate decision in the developing gonad depends on a complex network of interacting factors that converge on a critical threshold. To elucidate the transcriptional network underlying sex determination, we took the first expression quantitative trait loci (eQTL) approach in a developing organ. We identified reproducible differences in the transcriptome of the embryonic day 11.5 (E11.5) XY gonad between C57BL/6J (B6) and 129S1/SvImJ (129S1), indicating that the reported sensitivity of B6 to sex reversal is consistent with a higher expression of a female-like transcriptome in B6. Gene expression is highly variable in F2 XY gonads from B6 and 129S1 intercrosses, yet strong correlations emerged. We estimated the F2 coexpression network and predicted roles for genes of unknown function based on their connectivity and position within the network. A genetic analysis of the F2 population detected autosomal regions that control the expression of many sex-related genes, including Sry (sex-determining region of the Y chromosome) and Sox9 (Sry-box containing gene 9), the key regulators of male sex determination. Our results reveal the complex transcription architecture underlying sex determination, and provide a mechanism by which individuals may be sensitized for sex reversal.

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Published In

Genes Dev

DOI

EISSN

1549-5477

Publication Date

November 1, 2009

Volume

23

Issue

21

Start / End Page

2521 / 2536

Location

United States

Related Subject Headings

  • Y Chromosome
  • X Chromosome
  • Sex Determination Processes
  • SOX9 Transcription Factor
  • Quantitative Trait Loci
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Gonads
  • Genetic Variation
 

Citation

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Munger, S. C., Aylor, D. L., Syed, H. A., Magwene, P. M., Threadgill, D. W., & Capel, B. (2009). Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal. Genes Dev, 23(21), 2521–2536. https://doi.org/10.1101/gad.1835809
Munger, Steven C., David L. Aylor, Haider Ali Syed, Paul M. Magwene, David W. Threadgill, and Blanche Capel. “Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal.Genes Dev 23, no. 21 (November 1, 2009): 2521–36. https://doi.org/10.1101/gad.1835809.
Munger SC, Aylor DL, Syed HA, Magwene PM, Threadgill DW, Capel B. Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal. Genes Dev. 2009 Nov 1;23(21):2521–36.
Munger, Steven C., et al. “Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal.Genes Dev, vol. 23, no. 21, Nov. 2009, pp. 2521–36. Pubmed, doi:10.1101/gad.1835809.
Munger SC, Aylor DL, Syed HA, Magwene PM, Threadgill DW, Capel B. Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal. Genes Dev. 2009 Nov 1;23(21):2521–2536.

Published In

Genes Dev

DOI

EISSN

1549-5477

Publication Date

November 1, 2009

Volume

23

Issue

21

Start / End Page

2521 / 2536

Location

United States

Related Subject Headings

  • Y Chromosome
  • X Chromosome
  • Sex Determination Processes
  • SOX9 Transcription Factor
  • Quantitative Trait Loci
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Gonads
  • Genetic Variation