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A 11.7-kb deletion triggers intersexuality and polledness in goats

Nature Genetics volume 29, pages 453–458 (2001)Cite this article

Abstract

Mammalian sex determination is governed by the presence of the sex determining region Y gene (SRY) on the Y chromosome1. Familial cases of SRY-negative XX sex reversal are rare in humans, often hampering the discovery of new sex-determining genes2,3. The mouse model is also insufficient to correctly apprehend the sex-determination cascade, as the human pathway is much more sensitive to gene dosage4,5,6. Other species might therefore be considered in this respect7. In goats, the polled intersex syndrome (PIS) mutation associates polledness and intersexuality8,9. The sex reversal affects exclusively the XX individuals in a recessive manner, whereas the absence of horns is dominant in both sexes. The syndrome is caused by an autosomal gene located at chromosome band 1q43 (ref. 9), shown to be homologous to human chromosome band 3q23 (ref. 10). Through a positional cloning approach, we demonstrate that the mutation underlying PIS is the deletion of a critical 11.7-kb DNA element containing mainly repetitive sequences. This deletion 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 humans11. These two genes are located 20 and 200 kb telomeric from the deletion, respectively.

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Figure 1: Genomic description of the PIS locus.
Figure 2: FOXL2 and PISRT1 tissue expression at different developmental stages.
Figure 3: A 'cloth-peg' model of gene transcription regulation by SRY.

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References

  1. Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P. & Lovell-Badge, R. Male development of chromosomally female mice transgenic for Sry. Nature 351, 117–121 (1991).

    Article  CAS  Google Scholar 

  2. Krob, G., Braun, A. & Kuhnle, U. True hermaphroditism: geographical distribution, clinical findings, chromosomes and gonadal histology. Eur. J. Pediatr. 153, 2–10 (1994).

    Article  CAS  Google Scholar 

  3. McElreavey, K., Vilain, E., Abbas, N., Herskowitz, I. & Fellous, M. A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc. Natl Acad. Sci. USA 90, 3368–3372 (1993).

    Article  CAS  Google Scholar 

  4. Swain, A., Narvaez, V., Burgoyne, P., Camerino, G. & Lovell-Badge, R. Dax1 antagonizes Sry action in mammalian sex determination. Nature 391, 761–767 (1998).

    Article  CAS  Google Scholar 

  5. Luo, X., Ikeda, Y. & Parker, K.L. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77, 481–490 (1994).

    Article  CAS  Google Scholar 

  6. Kreidberg, J.A. et al. WT-1 is required for early kidney development. Cell 74, 679–691 (1993).

    Article  CAS  Google Scholar 

  7. Vaiman, D. & Pailhoux, E. Mammalian sex reversal and intersexuality: deciphering the sex-determination cascade. Trends Genet. 16, 488–494 (2000).

    Article  CAS  Google Scholar 

  8. Asdell, S.A. The genetic sex on intersexual goats and a probable linkage with the gene for hornlessness. Science 99, 124 (1944).

    Article  CAS  Google Scholar 

  9. Vaiman, D. et al. Genetic mapping of the autosomal region involved in XX sex-reversal and horn development in goats. Mamm. Genome 7, 133–137 (1996).

    Article  CAS  Google Scholar 

  10. Vaiman, D. et al. High-resolution human/goat comparative map of the goat polled/intersex syndrome (PIS): the human homologue is contained in a human YAC from HSA3q23. Genomics 56, 31–39 (1999).

    Article  CAS  Google Scholar 

  11. Crisponi, L. et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nature Genet. 27, 159–166 (2001).

    Article  CAS  Google Scholar 

  12. Schibler, L., Cribiu, E.P., Oustry-Vaiman, A., Furet, J.P. & Vaiman, D. Fine mapping suggests that the goat Polled Intersex Syndrome and the human Blepharophimosis Ptosis Epicanthus Syndrome map to a 100-kb homologous region. Genome Res. 10, 311–318 (2000).

    Article  CAS  Google Scholar 

  13. Smale, S.T. & Baltimore, D. The “initiator” as a transcription control element. Cell 57, 103–113 (1989).

    Article  CAS  Google Scholar 

  14. Lawson, C.T. et al. Definition of the blepharophimosis, ptosis, epicanthus inversus syndrome critical region at chromosome 3q23 based on the analysis of chromosomal anomalies. Hum. Mol. Genet. 4, 963–967 (1995).

    Article  CAS  Google Scholar 

  15. De Baere, E. et al. Identification of BPESC1, a novel gene disrupted by a balanced chromosomal translocation, t(3;4)(q23;p15.2), in a patient with BPES. Genomics 68, 296–304 (2000).

    Article  CAS  Google Scholar 

  16. Praphanphoj, V. et al. Molecular cytogenetic evaluation in a patient with a translocation (3;21) associated with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES). Genomics 65, 67–69 (2000).

    Article  CAS  Google Scholar 

  17. Koopman, P. Sry and Sox9: mammalian testis-determining genes. Cell Mol. Life Sci. 55, 839–856 (1999).

    CAS  PubMed  Google Scholar 

  18. Arango, N.A., Lovell-Badge, R. & Behringer, R.R. Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell 99, 409–419 (1999).

    Article  CAS  Google Scholar 

  19. Giese, K., Cox, J. & Grosschedl, R. The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures. Cell 69, 185–195 (1992).

    Article  CAS  Google Scholar 

  20. Giese, K., Pagel, J. & Grosschedl, R. Distinct DNA-binding properties of the high mobility group domain of murine and human SRY sex-determining factors. Proc. Natl Acad. Sci. USA 91, 3368–3372 (1994).

    Article  CAS  Google Scholar 

  21. Aasen, E. & Medrano, J.F. Amplification of the ZFY and ZFX genes for sex identification in humans, cattle, sheep and goats. Biotechnology 8, 1279–1281 (1990).

    CAS  PubMed  Google Scholar 

  22. Vaiman, D. et al. A genetic linkage map of the male goat genome. Genetics 144, 279–305 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors wish to acknowledge the work of R. Faugeras for sequencing and the excellent technical assistance of B. Jego. We thank J. Hervieu and J.F. Alkombre for help with goat breeding and management. We wish to acknowledge J.L. Vilotte for critical reading of the manuscript. This work was carried out with INRA AIP grants “Sex autosomal determination in goats and pigs” and “Genome and function”.

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Author notes

  1. Eric Pailhoux and Daniel Vaiman: These authors contributed equally to the experimental part of this work.

Authors and Affiliations

  1. Département de Physiologie Animale INRA, Laboratoire de Biologie du Développement et Biotechnologies, Centre de Recherches de Jouy-en-Josas, Jouy-en-Josas, 78352, Paris, France

    Eric Pailhoux, Bernard Vigier, Nathalie Servel & Corinne Cotinot

  2. Département de Génétique Animale, Laboratoire de Génétique biochimique et de Cytogénétique, INRA, Centre de Recherches de Jouy-en-Josas, Jouy-en-Josas, 78352, Paris, France

    Stéphane Chaffaux, Sead Taourit, Jean-Pierre Furet, François Grosclaude, Edmond P. Cribiu & Daniel Vaiman

  3. Laboratoire d'Immunogénétique Humaine, Institut Pasteur, 25 rue du Dr. Roux, 75015, Paris, France

    Marc Fellous

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  1. Eric Pailhoux
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Correspondence to Daniel Vaiman.

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Pailhoux, E., Vigier, B., Chaffaux, S. et al. A 11.7-kb deletion triggers intersexuality and polledness in goats. Nat Genet 29, 453–458 (2001). https://doi.org/10.1038/ng769

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