Nature Genetics
29, 453 - 458 (2001)
Published online: 19 November 2001; | doi:10.1038/ng769
A 11.7-kb deletion triggers intersexuality and polledness in goatsEric Pailhoux1, 4, Bernard Vigier1, Stéphane Chaffaux2, Nathalie Servel1, Sead Taourit2, Jean-Pierre Furet2, Marc Fellous3, François Grosclaude2, Edmond P. Cribiu2, Corinne Cotinot1
& Daniel Vaiman2, 41
Laboratoire de Biologie du Développement et Biotechnologies, Département de Physiologie Animale INRA, Centre de Recherches de Jouy-en-Josas, 78352 Jouy-en-Josas, Paris, France. 2
Laboratoire de Génétique biochimique et de Cytogénétique, Département de Génétique Animale, INRA, Centre de Recherches de Jouy-en-Josas, 78352 Jouy-en-Josas, Paris, France. 3
Laboratoire d'Immunogénétique Humaine, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France. 4
These authors contributed equally to the experimental part of this work.
Correspondence should be addressed to Daniel Vaiman vaiman@jouy.inra.frMammalian 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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