OMIA:000393-9913 : Tetragametic chimerism (including Freemartin) in Bos taurus (taurine cattle)

In other species: dog , horse , pig , red deer , sheep , bighorn sheep , water buffalo

Categories: Reproductive system phene

Mendelian trait/disorder: unknown

Considered a defect: yes

Cross-species summary: This is a type of sex chromosome difference of sexual development (DSD). Tetragametic chimerism is a rare, sex chromosome difference of sex development characterized by the two different haploid sets of maternal and paternal chromosomes and variable phenotype - from normal male or female genitalia, to different degrees of ambiguous genitalia, and often infertility. Also, in the cases of monochorionic dizygotic twins, it can be confined to blood of both twins. [updated from Orphanet : 199310 ] Freemartin or free-martin is an infertile female animal which is the twin of a male animal whose anti-Müllerian hormones affected its development in utero. Genetically the animals are chimeric (microchimerism, XX/XY leukocyte chimerism) - some stem cells from the male twin are received during in utero development via vascular connections between placentas. The condition is mostly reported in ruminants due to their multicotyledonary placenta type. Phene was renamed to 'Tetragametic chimerism' [16/11/2022]

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:000393-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.

2023 Hunt, H.L., Kirkpatrick, B.W. :
Degree of leukochimerism with calf age in Angus-crossbred twin sets. Anim Genet , 2023. Pubmed reference: 37558935. DOI: 10.1111/age.13349.
Lindtke, D., Seefried, F.R., Drögemüller, C., Neuditschko, M. :
Increased heterozygosity in low-pass sequencing data allows identification of blood chimeras in cattle. Anim Genet , 2023. Pubmed reference: 37313694. DOI: 10.1111/age.13334.
2022 Szczerbal, I., Nowacka-Woszuk, J., Stachowiak, M., Lukomska, A., Konieczny, K., Tarnogrodzka, N., Wozniak, J., Switonski, M. :
XX/XY chimerism in internal genitalia of a virilized heifer. Animals (Basel) 12:2932, 2022. Pubmed reference: 36359056. DOI: 10.3390/ani12212932.
2003 Meinecke, B., Kuiper, H., Drogemuller, C., Leeb, T., Meinecke-Tillmann, S. :
A mola hydatidosa coexistent with a foetus in a bovine freemartin pregnancy Placenta 24:107-12, 2003. Pubmed reference: 12495666.
1999 Cavalieri, J., Farin, P.W. :
Birth of a Holstein freemartin calf co-twinned to a schistosomus reflexus fetus Theriogenology 52:815-826, 1999. Pubmed reference: 10735122.
Ennis, S., Vaughan, L., Gallagher, T.F. :
The diagnosis of freemartinism in cattle using sex-specific DNA sequences Research in Veterinary Science 67:111-112, 1999. Pubmed reference: 10425251. DOI: 10.1053/rvsc.1998.0286.
Kannan, T.P., Thangaraju, P., Asokan, S.A. :
Karyological study of a Holstein Friesian crossbred freemartin Indian Veterinary Journal 76:450-451, 1999.
Nouri, M., Kohli, R.N. :
Induction of lactation in two freemartin heifers Indian Journal of Animal Sciences 69:413-414, 1999.
1997 Jankowski, R.A., Ildstad, S.T. :
Chimerism and tolerance - from freemartin cattle to neonatal mice to humans Human Immunology 52:155-161, 1997. Pubmed reference: 9077564. DOI: 10.1016/S0198-8859(96)00290-X.
Mommens, G., Vanzeveren, A., Peelman, L. :
Detection of freemartins by a Y chromosome specific DNA sequence [Dutch] Vlaams Diergeneeskundig Tijdschrift 66:88-92, 1997.
Satoh, S., Hirata, T.I., Miyake, Y.I., Kaneda, Y. :
The possibility of early estimation for fertility in bovine heterosexual twin females Journal of Veterinary Medical Science 59:221-222, 1997. Pubmed reference: 9101484.
1995 Fujishiro, A., Kawakura, K., Miyake, Y.I., Kaneda, Y. :
A fast, convenient diagnosis of the bovine freemartin syndrome using polymerase chain reaction Theriogenology 43:883-891, 1995.
Justi, A., Hecht, W., Herzog, A., Speck, J. :
Comparison of different methods for the diagnosis of freemartins - polymerase chain reaction, blood group serology and karyotyping [German] Deutsche Tierarztliche Wochenschrift 102:471-474, 1995. Pubmed reference: 8591746.
Kadokawa, H., Minezawa, M., Yamamoto, Y., Takahashi, M., Shimada, K., Takahashi, H., Kariya, T. :
Freemartinism among singleton bovine females born from multiple embryo transfer Theriogenology 44:295-306, 1995.
1994 Edwards, J.F., Gallagher, D.S., Prakash, B. :
Urethral atresia with uroperitoneum in a newborn bovine freemartin. Vet Pathol 31:117-9, 1994. Pubmed reference: 8140717. DOI: 10.1177/030098589403100118.
Khan, M.Z., Foley, G.L. :
Retrospective studies on the measurements, karyotyping and pathology of reproductive organs of bovine freemartins. J Comp Pathol 110:25-36, 1994. Pubmed reference: 8040370. DOI: 10.1016/s0021-9975(08)80267-8.
1993 Olsaker, I., Jørgensen, C.B., Hellemann, A.L., Thomsen, P.D., Lie, O. :
A fast and highly sensitive method for detecting freemartinism in bovine twins using immunomagnetic beads and Y-specific PCR primers. Anim Genet 24:311-3, 1993. Pubmed reference: 8239077. DOI: 10.1111/j.1365-2052.1993.tb00319.x.
van Haeringen, H., Hradil, R. :
[Twins in cattle. Freemartin or not? Current aspects]. Tijdschr Diergeneeskd 118:648-9, 1993. Pubmed reference: 8236226.
1992 Buoen, L.C., Zhang, T.Q., Weber, A.F., Anderson, M.R., Ruth, G.R. :
The requirement of fibroblasts to confirm the identity of cytogenetic centric fusion (CF) carriers in same-sex twin cattle. J Vet Diagn Invest 4:212-4, 1992. Pubmed reference: 1616994. DOI: 10.1177/104063879200400224.
Fernandezgarcia, J.L., Martineztrancon, M., Rabasco, A., Padilla, J.A. :
A case of 1/29 Robertsonian translocation in both cellular lines of a freemartin heifer. Journal of Heredity 83:393-395, 1992.
Grobet, L., Charlier, C., Schwers, A., Hanset, R. :
[Detection of freemartinism by means of DNA finger prints and of a bovine Y-specific probe.] [French] Annales de Medecine Veterinaire 136:41-50, 1992.
Plante, Y., Schmutz, S.M., Lang, K.D., Moker, J.S. :
Detection of leucochimaerism in bovine twins by DNA fingerprinting. Anim Genet 23:295-302, 1992. Pubmed reference: 1503268. DOI: 10.1111/j.1365-2052.1992.tb00151.x.
Schellander, K., Peli, J., Taha, T.A., Kopp, E., Mayr, B. :
Diagnosis of bovine freemartinism by the polymerase chain reaction method. Anim Genet 23:549-51, 1992. Pubmed reference: 1362861. DOI: 10.1111/j.1365-2052.1992.tb00177.x.
Separovic, E.R., Soldatovic, B., Veselinovic, S., Medic, D., Andjelkovic, M. :
Structural changes on chromosomes of heterosexual cattle twins. Acta Veterinaria - Beograd 42:15-19, 1992.
1991 Grobet, L., Charlier, C., Hanset, R. :
DNA fingerprints and leucochimerism in bovine dizygotic twins. Annales de Medecine Veterinaire 135:353-360, 1991.
1990 Dominguez, M.M., Liptrap, R.M., Croy, B.A., Basrur, P.K. :
Hormonal correlates of ovarian alterations in bovine freemartin fetuses. Animal Reproduction Science 22:181-201, 1990.
1989 Murakami, R., Miyake, Y., Kaneda, Y. :
Cases of XY female, single-birth freemartin and trisomy (61, XX, +20) observed in cytogenetical studies on 18 sterile heifers. Nihon Juigaku Zasshi 51:941-5, 1989. Pubmed reference: 2607745. DOI: 10.1292/jvms1939.51.941.
1988 Desai, D.S., Krishnaswamy, A., Narayana, K., Nagaraja, C.S., Degde, B.P. :
Cytogenetic studies on heterosexual twins in cattle Indian Journal of Dairy Science 41:21-23, 1988.
Romagnano, A., Tiemann, M., Niar, A., Helie, O., King, W.A. :
[Freemartinism in domestic animals] Medicin veterinaire du Quebec 18:79-84, 1988.
1987 Syed, M., Nes, N., Ronningen, K. :
The significance of chromosome studies in animal breeding in Norway Journal of Animal Breeding and Genetics 104:113-120, 1987.
1986 Rajcan-Separovic, E., Soldatovic, B., Ninkov, D., Zimonjic, D. :
[Cytogenetic and anatomical examination of freemartin heifers] Veterinarski Glasnik 40:447-452, 1986.
1981 Dunn, H.O., Johnson, R.H., Quaas, R.L. :
Sample size for detection of Y-chromosomes in lymphocytes of possible freemartins Cornell Veterinarian 71:297-304, 1981. Pubmed reference: 7196308.
1979 Dunn, H.O., McEntee, K., Hall, C.E., Johnson, R.H.Jr., Stone, W.H. :
Cytogenetic and reproductive studies of bulls born co-twin with freemartins Journal of Reproduction and Fertility 57:21-30, 1979. Pubmed reference: 574547.
1978 Kastli, F., Hall, J.G. :
Cattle twins and freemartin diagnosis Veterinary Record 102:80-83, 1978. Pubmed reference: 636235.
1977 Dain, A.R., Bridge, P.S. :
A freemartin calf with XX/XXY mosaicism Annales de Genetique et de Selection Animale 9:533 only, 1977.
Eldridge, F.E., Blazak, W.F. :
Chromosomal analysis of fertile female heterosexual twins in cattle Journal of Dairy Science 60:458-463, 1977. Pubmed reference: 845292. DOI: 10.3168/jds.S0022-0302(77)83888-5.
1974 Marcum, J.B. :
The freemartin syndrome Animal Breeding Abstracts 42:227-242, 1974.
1969 Short, R.V., Smith, J., Mann, T., Evans, E.R., Hallett, J., Fryer, A., Hamerton, J.L. :
Cytogenetic and endocrine studies of a freemartin heifer and its bull co-twin Cytogenetics 8:369-388, 1969. Pubmed reference: 5823570.
1965 Bertrand, M. :
[Freemartinism] Revue de Medecine Veterinaire 116:575-596, 1965.
Jainudeen, M.R., Hafez, E.S.E. :
Attempts to induce bovine freemartinism experimentally Journal of Reproduction and Fertility 10:281-283, 1965. Pubmed reference: 5891100.
Makino, S., Muramoto, J., Ishikawa, T. :
Notes on XX/XY mosaicism in cells of various tissues of heterosexual twins of cattle Proceedings of the Japan Academy 41:414-418, 1965.
1964 Committee for the Control of Sterility, Ghent Vete, School. Report. :
[Committee for the Control of Sterility, Ghent Veterinary School. Report for the year 1963] Vlaams Diergeneeskundig Tijdschrift 33:62-70, 1964.
Rajakoski, E., Hafez, E.S.E. :
Cytological differentiation of fetal bovine gonads Cytogenetics 3:193-200, 1964.
1963 Bouquet, Y., Willems, A.E.R. :
[Some aspects and results of research into blood groups of cattle twins] Annales de Medecine Veterinaire 107:552-580, 1963.
Rajakoski, E., Hafez, E.S.E. :
Derivatives of cortical cords in adult freemartin gonads of bovine quintuplets Anatomical Record 147:457-497, 1963. Pubmed reference: 14101909.
Rajakoski, E., Hafez, E.S.E. :
Gradient transformation of freemartin gonads in Bos taurus Proceedings of the Fifteenth International Congress on Zoology, Washington 2:228 only, 1963.
1962 Gasparski, J. :
[Investigations on cattle twins. Attempts to determine the blood types of cattle twins on the basis of the blood types of their progeny] Roczniki Nauk Rolniczych. Seria B : Zootechniczna 79:167-173, 1962.
Ohno, S., Trujillo, J.M., Stenius, C., Christian, L.C., Teplitz, R.L. :
Possible germ cell chimeras among newborn dizygotic twin calves (Bos taurus) Cytogenetics 1:258-265, 1962. Pubmed reference: 13939685.
1959 Rasmusen, B.A. :
Blood groups, disputed parentage, twins and freemartins in cattle Illinois Veterinarian 2:31-34, 1959.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Imke Tammen2 on 16 Nov 2022