OMIA 000483-9925 : Polled/Horns in Capra hircus

In other species: cattle , sheep , water buffalo , bighorn sheep , kouprey , domestic yak

Possibly relevant human trait(s) and/or gene(s) (MIM number): 110100

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2001

Cross-species summary: There is substantial variation in the extent of horn growth, making classification difficult. However, in general, the presence or absence of horns can be attributed to the action of two alleles at an autosomal locus. The type of gene action varies considerably between and among species.

Species-specific name: Polled/Intersex syndrome (PIS)

Species-specific symbol: PIS

Species-specific description: In goats, intersexuality is a recessive trait associated with the dominant allele for the absence of horns (polled). Some XY goats that are homozygous for the polled allele, are sterile. Most XX goats that are homozygous for the polled allele, show signs of intersexuality, ranging from almost normal female to almost male in external appearance and in development of reproductive tracts and organs. Paihoux et al. (1994) showed that three polled goats with ambiguous genitalia had a normal XX karyotype. These authors also showed an absence of Y-chromosome DNA in these animals, thus ruling out Y-X translocation as a cause of the intersexuality. Similar observations on seven intersex goats were made by Vaiman et al. (1997). (Information complied by Helena Axtoll, Uppsala, March 1998)

History: This appears to be the first published example of the application of the goat SNP50 bead chip.

Inheritance: As in other species, polledness in goats is a single-locus autosomal dominant trait. Unlike in other species, the same allele that confers polledness is autosomal recessive for intersexuality (see Summary above). This somewhat unusual situation was first reported by Asdell (1944).

Mapping: A linkage analysis by Vaiman et al. (1997) showed that the locus for polledness/intersex (PIS) is located in the distal region of chromosome 1. (Information compiled by Helena Axtoll, Uppsala, March 1998). The PIS region was narrowed to 1Mb within band 1q43 by Vaiman et al. (1999). Schibler et al. (2000) narrowed this to 100 kb contained within one BAC clone.

Using the goat SNP50 Bead Chip, Kijas et al. (2012) "collected and analysed genotypes from 52 088 SNPs in Boer, Cashmere and Rangeland goats that had both polled and horned individuals." In confirming the location of the polled locus on chromosome CHI1, they confirmed the mapping of this locus to a "769-kb critical interval . . . , confirming the genetic basis [of the polled intersex syndrome] in non-European animals is the same as identified previously in Saanen goats. Interestingly, analysis of the haplotypes carried by a small set of sex-reversed animals, known to be associated with polledness, revealed some animals carried the wild-type chromosome associated with the presence of horns. This suggests a more complex basis for the relationship between polledness and the intersex condition than initially thought".

Molecular basis: Exon-trapping and subsequent sequencing of the BAC clone that spanned the PIS locus enabled Pailhoux et al. (2001) to identify a gene they called PIS-regulated transcript 1 (PISRT1). The then showed that PIS is due to an 11.7 kb deletion of mainly repetitive DNA which affects the transcription of PISRT1 and a neighbouring gene FOXL2. As noted by the authors, "These two genes are located 20 and 200 kb telomeric from the deletion, respectively". Interestingly, a mutation of FOXL2 in humans gives rise to Blepharophimosis Ptosis Epicanthus inversus Syndrome (BPES; see MIM hyperlink above) which is a disorder somewhat similar to PIS.

Further investigations enabled Pailhoux et al. (2005) to conclude that the deletion "is composed for 80% of two copies of a partial ruminant LINE (2.2 and 2.6 kilobases), oriented head to head, 25 kilobases apart from PISRT1." They also reported that "FOXL2 may be an ovary-differentiating gene, and the non-coding RNA PISRT1, an anti-testis factor repressing SOX9, a key regulator of testis differentiation. Under this hypothesis, SRY, the testis-determining factor would inhibit these two genes in the gonads of XY males, to ensure testis differentiation."

Allais-Bonnet et al. (2013) established a link between polledness in goats and cattle when they discovered that a trait strongly associated with polledness in cattle, namely two rows of eyelashes (distichiasis; OMIA 001841-9913), is caused in humans by mutations in FOXC2, which is a paralogue of FOXL2. Subsequent gene expression studies of this gene in tissues from polled and horned cattle led these authors to conclude that in both species "FOXL2 is involved in the negative regulation of horn bud differentiation (perhaps to control the diameter of the horn bud or to prevent horn growth before birth)".

Boulanger et al. (2014) provided strong evidence that "FOXL2 [is] a bona fide female sex-determining gene in the goat", i.e. that loss of function of FOXL2 is a sufficient explanation for PIS.

Clinical features: Vaiman et al. (1997) reported that all seven XX intersexes had two inguinally-located udders. Half the intersexes appeared to be closer to the female phenotype, and the other half were closer to males.The gonads of all animals contained seminiferous tubules lined by Sertoli cells. No germ cells were present. (Information collated by Helen Axtoll, Uppsala, March 1998)

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
FOXL2 forkhead box L2 Capra hircus - no genomic information (-..-) FOXL2 Homologene, Ensembl, NCBI gene

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2014 Boulanger, L., Pannetier, M., Gall, L., Allais-Bonnet, A., Elzaiat, M., Le Bourhis, D., Daniel, N., Richard, C., Cotinot, C., Ghyselinck, N.B., Pailhoux, E. :
FOXL2 Is a Female Sex-Determining Gene in the Goat. Curr Biol :, 2014. Pubmed reference: 24485832. DOI: 10.1016/j.cub.2013.12.039.
Canisso, I., Coffee, L., Ortved, K., Fubini, S., Monteagudo, L., Schlafer, D., Gilbert, R. :
Bilateral Sertoli and Interstitial Cell Tumours in Abdominal Testes of a Goat with Polled Intersex Syndrome (PIS). Reprod Domest Anim :, 2014. Pubmed reference: 25219569. DOI: 10.1111/rda.12408.
2013 Allais-Bonnet, A., Grohs, C., Medugorac, I., Krebs, S., Djari, A., Graf, A., Fritz, S., Seichter, D., Baur, A., Russ, I., Bouet, S., Rothammer, S., Wahlberg, P., Esquerré, D., Hoze, C., Boussaha, M., Weiss, B., Thépot, D., Fouilloux, M.N., Rossignol, M.N., van Marle-Köster, E., Hreiðarsdóttir, G.E., Barbey, S., Dozias, D., Cobo, E., Reversé, P., Catros, O., Marchand, J.L., Soulas, P., Roy, P., Marquant-Leguienne, B., Le Bourhis, D., Clément, L., Salas-Cortes, L., Venot, E., Pannetier, M., Phocas, F., Klopp, C., Rocha, D., Fouchet, M., Journaux, L., Bernard-Capel, C., Ponsart, C., Eggen, A., Blum, H., Gallard, Y., Boichard, D., Pailhoux, E., Capitan, A. :
Novel insights into the bovine polled phenotype and horn ontogenesis in Bovidae. PLoS One 8:e63512, 2013. Pubmed reference: 23717440. DOI: 10.1371/journal.pone.0063512.
Szatkowska, I. , Jedrzejczak, M., Dybus, A., Wiszniewska, B., Udała, J., Zaborski, D., Wojcik, J., Stankiewicz, T. :
Histological, molecular and transcriptional analysis of PIS goats Small Ruminant Research :, 2013. DOI: 10.1016/j.smallrumres.2013.11.009.
2012 Kijas, J.W., Ortiz, J.S., McCulloch, R., James, A., Brice, B., Swain, B., Tosser-Klopp, G. :
Genetic diversity and investigation of polledness in divergent goat populations using 52 088 SNPs. Anim Genet :, 2012. Pubmed reference: 23216229. DOI: 10.1111/age.12011.
Pannetier, M., Elzaiat, M., Thépot, D., Pailhoux, E. :
Telling the story of XX sex reversal in the goat: highlighting the sex-crossroad in domestic mammals. Sex Dev 6:33-45, 2012. Pubmed reference: 22094227. DOI: 10.1159/000334056.
Yang, B., Jia, L.L., Zhao, D.C., Meng, L.Y., Liu, X.F., Zhang, Y.J., Zhang, W.G., Li, J.Q. :
[Detection and application of PIS genetic deficiency gene in dairy goat]. Yi Chuan 34:895-900, 2012. Pubmed reference: 22805216.
2011 Yokota, S., Matsuu, A., Morita, T., Tsuka, T., Hishinuma, M., Minami, S., Hikasa, Y. :
Polled Intersex Syndrome with Urethral Atresia in a Goat. J Vet Med Sci :, 2011. Pubmed reference: 21646753.
2005 Pailhoux, E., Vigier, B., Schibler, L., Cribiu, EP., Cotinot, C., Vaiman, D. :
Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation. Genet Sel Evol 37 Suppl 1:S55-64, 2005. Pubmed reference: 15601595. DOI: 10.1051/gse:2004025.
Pannetier, M., Renault, L., Jolivet, G., Cotinot, C., Pailhoux, E. :
Ovarian-specific expression of a new gene regulated by the goat PIS region and transcribed by a FOXL2 bidirectional promoter. Genomics 85:715-26, 2005. Pubmed reference: 15885498. DOI: 10.1016/j.ygeno.2005.02.011.
2004 Nikic, S., Vaiman, D. :
Conserved patterns of gene expression in mice and goats in the vicinity of the Polled Intersex Syndrome (PIS) locus. Chromosome Res 12:465-74, 2004. Pubmed reference: 15252242. DOI: 10.1023/B:CHRO.0000034746.46789.e0.
2001 Pailhoux, E., Vigier, B., Chaffaux, S., Servel, N., Taourit, S., Furet, J.P., Fellous, M., Grosclaude, F., Cribiu, E.P., Cotinot, C., Vaiman, D. :
A 11.7-kb deletion triggers intersexuality and polledness in goats Nature Genetics 29:453-458, 2001. Pubmed reference: 11726932. DOI: 10.1038/ng769.
2000 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 Research 10:311-318, 2000. Pubmed reference: 10720572.
1999 Vaiman, D., Schibler, L., Oustry-Vaiman, A., Pailhoux, E., Goldammer, T., Stevanovic, M., Furet, J.P., Schwerin, M., Cotinot, C., Fellous, M., Cribiu, E.P. :
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. Pubmed reference: 10036183. DOI: 10.1006/geno.1998.5691.
1998 Flores, J.M., Sanchez, M.A., Gonzalez, M., Pizarro, M. :
Caprine testicular hypoplasia associated with sexual reversion decreases the expression of insulin-like growth factor ii (igf-ii) mrna in testes Animal Reproduction Science 52:279-288, 1998. Pubmed reference: 9821502.
Lauvergne, J.J., Bouchel, D., Minivielle, F. :
Morpho-biometrical study of rove goats - iii - horns length (hl) in both sexes and indexes of sexual dimorphism of horns (isdh) [French] Revue de Medecine Veterinaire 149:141-148, 1998.
1997 Hague, B.A., Hooper, R.N. :
Cosmetic dehorning in goats Veterinary Surgery 26:332-334, 1997. Pubmed reference: 9232792.
Vaiman, D., Pailhoux, E., Schibler, L., Oustry, A., Chaffaux, S., Cotinot, C., Fellous, M., Cribiu, E.P. :
Genetic mapping of the polled/intersex locus (pis) in goats Theriogenology 47:103-109, 1997.
1996 Flores, J.M., Sanchez, M.A., Rodriguez, A., Rex, E.M. :
Histopathological alterations of lamina propria and sertoli cells in severe testicular hypoplasia in polled goats Reproduction in Domestic Animals 31:349-352, 1996.
Roberts, S.C. :
The evolution of hornedness in female ruminants [Review] Behaviour 133:399-442, 1996.
Vaiman, D., Koutita, O., Oustry, A., Elsen, J.M., Manfredi, E., Fellous, M., Cribiu, E.P. :
Genetic mapping of the autosomal region involved in XX sex-reversal and horn development in goats Mammalian Genome 7:133-137, 1996. Pubmed reference: 8835530.
1995 Hull, B.L. :
Dehorning the adult goat Veterinary Clinics of North America - Food Animal Practice 11:183-185, 1995.
1993 Margetin, M. :
Visible Genetic Profile and Polymorphic Systems in Goats Raised in Slovakia Zivocisna Vyroba 38:491-501, 1993.
Yadav, B.R., Singh, C., Kumar, P., Tomer, O.S., Yadav, J.S. :
Morphological, Anatomical and Cytogenetical Investigations in Sexually Anomalous Goats Small Ruminant Research 11:331-342, 1993.
1990 Vallenzasca, C., Galli, A. :
Cytogenetical and Histopathologic Study of 2 Cases of Polled Goats Andrologia 22:289-290, 1990. Pubmed reference: 2240625.
1988 Millar, P. :
The principal loci with visible effects in goats :41-51, 1988.
Ramadan, R.O., Hassan, A.M.E. :
Intersexuality in goats New Zealand Veterinary Journal 36:120-124, 1988.
1987 Lauvergne, J.J., Renieri, C., Audiot, A. :
Estimating erosion of phenotypic variation in a French goat population Journal of Heredity 78:307-314, 1987. Pubmed reference: 3680926.
Rodrigues, M.T., Espeschit, C.J.B. :
[Hornlessness and the incidence of intersexuality in goats] Informe Agropecuaria 13:12-16, 1987.
1985 Bacalhau, A.S., Souza, W.H., Rodrigues, A., Pant, K.P. :
[Polledness as a factor affecting intersexuality in German Fawn kids in Paraiba] Revista Brasileira de Reproducao Animal 9:35-39, 1985.
1981 Constantinou, A., Louca, A., Mavrogenis, A.P. :
The effect of the gene for polledness on conception rate and litter size in the Damascus goat Annales de Genetique et de Selection Animale 13:111-118, 1981.
Ricordeau, G., Sanchez, F :
Horned gene frequencies in 4 French goat breeds Annales de Genetique et de Selection Animale 13:353-, 1981.
Ricordeau, G., Sanchez, G.F.F :
[Changes in the frequencies of horned animals in four types of French goat] Annales de Genetique et de Selection Animale 13:353-362, 1981.
1969 Basrur, P.K. :
Some thoughts on the association of polled trait and intersexuality in goats Annales de Genetique et de Selection Animale 1:439-446, 1969.
Lauvergne, J.J. :
Progress in genetic knowledge of intersexuality associated with polledness in the goat of alpine origin Annales de Genetique et de Selection Animale 1:403-412, 1969.
Lauvergne, J.J. :
Frequency at equilibrium of the gene of alpine origin responsible for polledness and intersexuality in some populations of goats Annales de Genetique et de Selection Animale 1:413-422, 1969.
1967 Ricordeau, G., Lauvergne, J.J. :
A single genetic hypothesis to account for the presence of intersexual animals, of males in excess and infertile males in 'Saanen' goats Annales de Zootechnie 16:323-334, 1967.
1963 Soller, M., Laor, M., Barnea, R., Weiss, Y., Ayalon, N. :
Polledness and infertility in male Saanen goats Journal of Heredity 54:237-240, 1963. Pubmed reference: 14086178.
1962 Laor, M., Barnea, R., Angel, H., Soller, M. :
Polledness and hermaphroditism in Saanen goats Israel Journal of Agricultural Research 12:83-88, 1962.
1961 Dejong, S. :
[Is there a relationship between the horned condition in goats and the production of intersexes, male infertility and disturbed sex ratio?] Tijdschrift voor Diergeneeskunde 86:58-59, 1961.
1960 Dejong, S. :
[Is there a relationship between the horned condition in goats and the production of intersexes, male infertility and disturbed sex ratio?] Geitehouder 23:40 only, 1960.
1945 Eaton, O.N. :
The Relation between Polled and Hermaphroditic Characters in Dairy Goats. Genetics 30:51-61, 1945. Pubmed reference: 17247145.
1944 Asdell, S.A. :
The genetic sex of intersexual goats and a probable linkage with the gene for hornlessness. Science 99:124, 1944. Pubmed reference: 17814292. DOI: 10.1126/science.99.2563.124.
1939 Eaton, O.N., Simmons, V.L. :
Hermaphrodism in milk goats Journal of Heredity 30:261-266, 1939.
1926 Lush, J.L. :
Inheritance of horns, wattles and colour in grade Toggenburg goats Journal of Heredity 17:73-90, 1926.

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