OMIA:002362-9940 : Fecundity, GDF9-related in Ovis aries (sheep)

In other species: dog , goat

Categories: Reproductive system phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 601918 (gene) , 618014 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2004

Species-specific symbol: FecG

Species-specific description: The following OMIA entries relating to specific variants in the GDF9 gene and their impact on fecundity have been incorporated into this entry: OMIA:001961-9940 Fecundity, Vacaria, FecG(V) (4th October 2021) OMIA:001763-9940 Fecundity, Norwegian White Sheep (4th October 2021) OMIA:001559-9940 Fecundity, Embrapa, FecG(E) (4th October 2021) OMIA:001801-9940 Fecundity, High fertility, FecG(H) (5th October 2021) OMIA:000385-9940 Fecundity, Thoka, FecG(T) (5th October)

History: A segregation analysis of Icelandic sheep by Jonmundsson and Adalsteinsson (1985) provided substantial evidence for a gene of large effect on litter size. These authors named the gene Thoka, after the ewe from which the gene appears to have originated. Heterozygotes give birth to an extra 0.64 lambs, on average. In a segregation analysis of data from a Cheviot flock into which the Thoka gene was introduced via Icelandic rams, Walling et al. (2002) confirmed the existence of a gene of large effect on fecundity, but there was some evidence that this gene was present in the flock before the Icelandic introduction. Since this evidence is only preliminary, the gene will be assumed to be Thoka until further evidence is assembled [FN 13 Jan 2003] Hanrahan et al. (2004) reported a mutation in the gene GDF9 "associated with increased ovulation rate in heterozygous carriers and sterility in homozygous carriers" in the Irish Cambridge and Belclare breeds. They also reported that "This is the first time that a mutation in the gene for GDF9 has been found that causes increased ovulation rate and infertility in a manner similar to inactivating mutations in BMP15, and shows that GDF9 is essential for normal folliculogenesis in sheep. Furthermore, it is shown, for the first time in any species, that individuals with mutations in both GDF9 and BMP15 have a greater ovulation rate than sheep with either of the mutations separately."

Molecular basis: Hanrahan et al. (2004) identified a variant c.1184C>T, p.(S395F) which they named FecG(H), with G indicating the GDF9 gene and H indicating high fertility. These authors reported that "The effect of FecGH was 1.79 ± 0.548 (P < 0.01) in Belclare ewes and 2.35 ± 0.386 (P < 0.001) in Cambridge ewes" and that "All ewes that were homozygous for FecGH . . . were sterile". Nicol et al. (2009) identified the causal mutation of Thoka fecundity as "a single base change (A1279C) resulting in a non-conservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development". Silva et al. (2011) reported a missense mutation (c.1034T>G; p.Phe345Cys) in the GDF9 gene of Brazilian Santa Inês sheep, giving rise to increases of 82% and 58% for ovulation rate and prolificacy, respectively, compared with homozygous wild-type. They named this allele FecG(E), where E stands for Embrapa, the Brazilian Agricultural Research Corporation. Using the sheep SNP50 bead chip to conduct a GWAS for litter size estimated breeding value (EBV) on 378 progeny-tested Norwegian White Sheep rams, Våge et al. (2013) identified a QTL on chromosome OAR5, very near to the GDF9 gene, mutations in which have large effects on fecundity in other breeds of sheep. Subsequent sequencing of this gene in the most extreme sires revealed a SNP "(c.1111G>A), responsible for a Val->Met substitution at position 371 (V371M). This polymorphism has previously been identified in Belclare and Cambridge sheep, but was not found to be associated with fertility." The authors concluded that "Based on the estimated breeding values, daughters of AI rams homozygous for c.1111A will produce minimum 0.46 - 0.57 additional lambs compared to daughters of wild-type rams." Mullen and Hanrahan (2014) reported the same variant as having a significant effect on fecundity in Finnish Landrace (Finnsheep), and proposed that the variant be named FecG(F), where F is for Finnsheep. Souza et al. (2014) reported a variant in the GDF9 gene in the Ile de France breed in Brazil. The authors described its effect as "Vacaria heterozygotes had higher OR (P<0.001), averaging 2.1 +/- 0.1 when compared to 1.2 +/- 0.1 in wild-type ewes. The OR was also influenced by age, increasing in the second and third breeding seasons (P<0.001). In flocks segregating this allele, the LS was higher in mutant sheep (P<0.001), averaging 1.61 +/- 0.07 in heterozygotes and 1.29 +/- 0.03 in wild-type ewes. Analysis of homozygote reproductive tract morphology revealed uterine and ovarian hypoplasia. Ovarian follicles continue to develop up to small antral stages, although with abnormal oocyte morphology and altered arrangement of granulosa cells. After the collapse of the oocyte in most follicles, the remaining cells formed clusters that persisted in the ovary." Souza et al. (2014) named the variant Vacaria FecG(v) "after the city where the first flocks with this polymorphism were located". They reported it as a missense mutation: c.943C>T; p.Arg315Cys in the cleavage site of the propeptide encoded by GDF9. Bravo et al. (2016): Sequencing of the GDF9 revealed eight single nucleotide polymorphisms (SNPs), including seven documented and one novel SNP, named FecGA (Araucana) [c.750G>A; (p.Arg250Arg), ss1947221108] ... . Both the c.978A>G and c.994G>A SNPs [variant G5 and G6 reported by Hanrahan et al. (2004)] showed an association with LS (P < 0.05), but only c.994G>A is non-silent, leading to a p.Val332Ile substitution in a mature protein. ... Our results suggest that c.978A>G and c.994G>A SNPs are genetic markers for fecundity in ACS." Pérez-Ruiz et al. (2020) reported the FecG(E) variant having a major effect on fecundity in the Mexican Pelibuey breed. Holm et al. (2021) "analyzed samples from Icelandic sheep with the aim of identifying the genetic cause of the Icelandic Loa phenotype using three previously identified prolificacy genes as candidates. We demonstrate that a 4-bp frameshift deletion positioned in the mature region of the GDF9 protein in the Loa animals is a likely causal mutation for the observed increase in prolificacy; however, sequencing showed that not all ewes with a high number of offspring carried the deletion, suggesting the presence of a second mutation segregating within this group of animals." Zhao et al. (2023): "In this study, a single base editing system was used to edit the FecB and GDF9 gene to achieve a targeted site mutation from A to G and from C to T in Ouler Tibetan sheep fibroblasts, and to test its editing efficiency." This study involves genetically modified organisms (GMO) Ji et al. (2023) “performed an association analysis of the 13 new mutations and 7 known ovine prolificacy-related mutations [in the BMPRIB, GDF9, BMP15, LEPR, and B4GALNT2 genes] with litter size in Ujimqin, the F1 population of Dorper × Ujimqin crossbred, and the F1 population of Suffolk × Ujimqin crossbred. The results suggested that BMPR1B c.746A>G (FecB), GDF9 c.994A>G ... [variant G6 reported by Hanrahan et al. (2004)], and BMP15 c.31_33CTTinsdel (B1) may be potentially effective genetic markers to improve the litter size in sheep.”

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Belclare (Sheep) (VBO_0001322), Cambridge (Sheep) (VBO_0001355), Criollo araucana, Chile (Sheep) (VBO_0015719), Finnish Landrace (Sheep) (VBO_0001414), Gammelnorsk spaelsau, Norway (Sheep) (VBO_0016295), Icelandic (Sheep) (VBO_0001442), Ile-De-France (Sheep) (VBO_0001444), Pelibuey, Mexico (Sheep) (VBO_0015035), Santa Ines, Brazil (Sheep) (VBO_0015203).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GDF9 growth differentiation factor 9 Ovis aries 5 NC_056058.1 (42116604..42113878) GDF9 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
239 Wicklow Cheviot (Sheep) Fecundity, Thoka, FecG GDF9 FecG(T) missense Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545130T>G c.1279A>C p.(S427R) Oar_v3.1 position is g.41841117T>G; protein and cDNA positions are based on NP_001136360.2 and NM_001142888.2, respectively 2009 19713444 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.
242 Belclare (Sheep) Cambridge (Sheep) Fecundity, High fertility, FecG GDF9 FecG(H) missense Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545225G>A c.1184C>T p.(S395F) Oar_v3.1 position is g.41841212G>A; protein and cDNA position based on NP_001136360.2 and NM_001142888.2 respectively 2004 14627550 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.
243 Gammelnorsk spaelsau, Norway (Sheep) Fecundity, Norwegian White Sheep GDF9 FecG(F) missense Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545298C>T c.1111G>A p.(V371M) Oar_v3.1 position is g.41841285C>T, protein and cDNA positions based on NP_001136360.2 and NM_001142888.2, respectively rs403536877 2013 23280002 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.
240 Pelibuey, Mexico (Sheep) Santa Ines, Brazil (Sheep) Fecundity, Embrapa, FecG GDF9 FecG(E) missense Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545375A>C c.1034T>G p.(F345C) Oar_v3.1 position is g.41841362T>G; protein and cDNA position based on NP_001136360.2 and NM_001142888.2, respectively rs1092755620 2011 20528846 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.
1407 Icelandic (Sheep) Fecundity, Loa, FecG GDF9 FecG(L) deletion, small (<=20) Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545396_46545399del p.(N337Rfs*26) Oar_v3.1 position is g.41841383_41841386del 2021 34967038
246 Ile-De-France (Sheep) Fecundity, Vacaria, FecG GDF9 FecG(V) missense Naturally occurring variant Oar_rambouillet_v1.0 5 g.46545466G>A c.943C>T p.(R315C) Oar_v3.1 position is g.41841453G>A; protein and cDNA positions based on NP_001136360.2 and NM_001142888.2, respectively 2014 25039891 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool. The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries.

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002362-9940: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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.

2023 Amandykova, M., Orazymbetova, Z., Kapassuly, T., Kozhakhmet, A., Khamzina, S., Iskakov, K., Dossybayev, K. :
Detection of genetic variations in the GDF9 and BMP15 genes in Kazakh meat-wool sheep. Arch Anim Breed 66:401-409, 2023. Pubmed reference: 38205376. DOI: 10.5194/aab-66-401-2023.
Antonopoulou, D., Giantsis, I.A., Symeon, G.K., Avdi, M. :
Association of MTNR1A and GDF9 gene allelles with the reproductive performance, response to oestrus induction treatments and prolificacy, in improved and non-improved local indigenous sheep breeds. Reprod Domest Anim 58:1532-1541, 2023. Pubmed reference: 37668279. DOI: 10.1111/rda.14468.
Budiyanto, A., Hartanto, S., Widayanti, R., Setyawan, E.M.N., Wardono, H.P., Gustari, S. :
The relationship between G1 (c.260 G>A) and G4 (c.721 G>A) polymorphisms in the GDF9 gene and the litter size of sheep: A meta-analysis study. J Adv Vet Anim Res 10:599-607, 2023. Pubmed reference: 38370904. DOI: 10.5455/javar.2023.j715.
Ji, X., Cao, Z., Hao, Q., He, M., Cang, M., Yu, H., Ma, Q., Li, X., Bao, S., Wang, J., Tong, B. :
Effects of new mutations in BMPRIB, GDF9, BMP15, LEPR, and B4GALNT2 genes on litter size in sheep. Vet Sci 10:258, 2023. Pubmed reference: 37104413. DOI: 10.3390/vetsci10040258.
Marzanov, N.S., Devrishov, D.A., Ozerov, M.Y., Maluchenko, O.P., Marzanova, S.N., Shukurova, E.B., Koreckaya, E.A., Kantanen, J., Petit, D. :
The significance of a multilocus analysis for assessing the biodiversity of the Romanov sheep Breed in a comparative aspect. Animals (Basel) 13:1320, 2023. Pubmed reference: 37106883. DOI: 10.3390/ani13081320.
Pereira, A.H.R., Silveira, R.M.F., Carrara, E.R., de Moraes Silva, K., Lobo, R.N.B., de Faria, D.A., Caetano, A.R., Paiva, S.R., Landim, A.V. :
Assessment of FecG E genotypes on reproductive traits in Brazilian Morada Nova and Santa Inês sheep. Trop Anim Health Prod 55:413, 2023. Pubmed reference: 37994941. DOI: 10.1007/s11250-023-03822-x.
Zhao, Y., Zhang, Y., Yu, R., Wu, Y., Chen, Y., Zhao, R., Zhang, C., Su, J. :
[Single base editing system mediates site-directed mutagenesis of genes GDF9 and FecB in Ouler Tibetan sheep]. Sheng Wu Gong Cheng Xue Bao 39:204-216, 2023. Pubmed reference: 36738211. DOI: 10.13345/j.cjb.220427.
2021 Aboelhassan, D.M., Darwish, A.M., Ali, N.I., Ghaly, I.S., Farag, I.M. :
A study on mutation points of GDF9 gene and their association with prolificacy in Egyptian small ruminants. J Genet Eng Biotechnol 19:85, 2021. Pubmed reference: 34097165. DOI: 10.1186/s43141-021-00181-8.
Çelikeloğlu, K., Tekerli, M., Erdoğan, M., Koçak, S., Hacan, Ö., Bozkurt, Z. :
An investigation of the effects of BMPR1B, BMP15, and GDF9 genes on litter size in Ramlıç and Dağlıç sheep. Arch Anim Breed 64:223-230, 2021. Pubmed reference: 34159253. DOI: 10.5194/aab-64-223-2021.
Derks, M.F.L., Steensma, M. :
Review: Balancing selection for deleterious alleles in livestock. Front Genet 12:761728, 2021. Pubmed reference: 34925454. DOI: 10.3389/fgene.2021.761728.
Holm, L.E., Bendixen, C., Eythorsdottir, E., Hallsson, J.H. :
A frameshift deletion in the GDF9 gene in Icelandic Loa prolific sheep. Anim Genet 53:220-223, 2021. Pubmed reference: 34967038. DOI: 10.1111/age.13168.
Muñoz-García, C., Vaquera-Huerta, H., Gallegos-Sánchez, J., Becerril-Pérez, C.M., Tarango-Arámbula, L.A., Bravo-Vinaja, Á., Cortez-Romero, C. :
Influence of FecG^E mutation on the reproductive variables of Pelibuey ewes in the anestrus period. Trop Anim Health Prod 53:328, 2021. Pubmed reference: 34002300. DOI: 10.1007/s11250-021-02755-7.
Wang, F., Chu, M., Pan, L., Wang, X., He, X., Zhang, R., Tao, L., La, Y., Ma, L., Di, R. :
Polymorphism detection of GDF9 gene and its association with litter size in Luzhong mutton sheep (Ovis aries). Animals (Basel) 11, 2021. Pubmed reference: 33671790. DOI: 10.3390/ani11020571.
2020 Al-Mutar, H., Younis, L. :
Effect of point mutation in the growth differentiation factor 9 gene of oocytes on the sterility and fertility of Awassi sheep. Arch Razi Inst 75:101-108, 2020. Pubmed reference: 32292008. DOI: 10.22092/ari.2018.122232.1220.
Amirpour Najafabadi, H., Khansefid, M., Mahmoud, G.G., Zhou, H., Hickford, J.G.H. :
Identification of polymorphisms in the oocyte-derived growth differentiation growth factor 9 (GDF9) gene associated with litter size in New Zealand sheep (Ovis aries) breeds. Reprod Domest Anim 55:1585-1591, 2020. Pubmed reference: 32865284. DOI: 10.1111/rda.13813.
Pérez-Ruiz, E., Gallegos-Sánchez, J., Cortez-Romero, C., Segura-León, O.L., Salinas-Ruíz, J., Salazar-Ortiz, J. :
FecG^E mutation in Pelibuey sheep. Anim Genet 51:346-7, 2020. Pubmed reference: 31961953. DOI: 10.1111/age.12912.
Tong, B., Wang, J., Cheng, Z., Liu, J., Wu, Y., Li, Y., Bai, C., Zhao, S., Yu, H., Li, G. :
Novel variants in GDF9 Gene affect promoter activity and litter size in Mongolia sheep. Genes (Basel) 11:375, 2020. Pubmed reference: 32235645. DOI: 10.3390/genes11040375.
2019 Mohamed, S.E.I., Ahmed, R.M., Jawasreh, K.I.Z., Salih, M.A.M., Abdelhalim, D.M., Abdelgadir, A.W., Obeidat, M.T., Musa, L.M.A., Ahmed, M.A. :
Genetic polymorphisms of fecundity genes in Watish Sudanese desert sheep. Vet World 13:614-621, 2019. Pubmed reference: 32546903. DOI: 10.14202/vetworld.2020.614-621.
2018 Abdoli, R., Ziaeddin Mirhoseini, S., Ghavi Hossein-Zadeh, N., Zamani, P. :
Screening for Causative Mutations of Major Prolificacy Genes in Iranian Fat-Tailed Sheep. Int J Fertil Steril 12:51-55, 2018. Pubmed reference: 29334207. DOI: 10.22074/ijfs.2018.5247.
Pan, Z., Wang, X., Di, R., Liu, Q., Hu, W., Cao, X., Guo, X., He, X., Lv, S., Li, F., Wang, H., Chu, M. :
A 5-methylcytosine site of growth differentiation factor 9 (GDF9) gene affects its tissue-specific expression in sheep. Animals (Basel) 8, 2018. Pubmed reference: 30405007. DOI: 10.3390/ani8110200.
Shokrollahi, B., Morammazi, S. :
Polymorphism of GDF9 and BMPR1B genes and their association with litter size in Markhoz goats. Reprod Domest Anim 53:971-978, 2018. Pubmed reference: 29696699. DOI: 10.1111/rda.13196.
Tang, J., Hu, W., Di, R., Liu, Q., Wang, X., Zhang, X., Zhang, J., Chu, M. :
Expression analysis of the prolific candidate genes, BMPR1B, BMP15, and GDF9 in small tail Han ewes with three fecundity (FecB Gene) genotypes. Animals (Basel) 8, 2018. Pubmed reference: 30274220. DOI: 10.3390/ani8100166.
2017 Ahmad, H.I., Liu, G., Jiang, X., Edallew, S.G., Wassie, T., Tesema, B., Yun, Y., Pan, L., Liu, C., Chong, Y., Yu, Z.J., Jilong, H. :
Maximum-likelihood approaches reveal signatures of positive selection in BMP15 and GDF9 genes modulating ovarian function in mammalian female fertility. Ecol Evol 7:8895-8902, 2017. Pubmed reference: 29177034. DOI: 10.1002/ece3.3336.
El Fiky, Z.A., Hassan, G.M., Nassar, M.I. :
Genetic polymorphism of growth differentiation factor 9 (GDF9) gene related to fecundity in two Egyptian sheep breeds. J Assist Reprod Genet 34:1683-1690, 2017. Pubmed reference: 28762037. DOI: 10.1007/s10815-017-1007-2.
El-Seedy, A.S., Hashem, N.M., El-Azrak, K.M., Nour El-Din, A., Ramadan, T.A., Taha, T.A., Salem, M.H. :
Genetic screening of FecB, FecX<sup>G</sup> and FecX<sup>I</sup> mutations and their linkage with litter size in Barki and Rahmani sheep breeds. Reprod Domest Anim 52:1133-1137, 2017. Pubmed reference: 28585345. DOI: 10.1111/rda.13002.
Escobar-Chaparro, R.A., Guillén, G., Espejo-Galicia, L.U., Meza-Villalvazo, V.M., Peña-Castro, J.M., Abad-Zavaleta, J. :
qPCR and HRM-based diagnosis of SNPs on growth differentiation factor 9 (GDF9), a gene associated with sheep (Ovis aries) prolificacy. 3 Biotech 7:204, 2017. Pubmed reference: 28667646. DOI: 10.1007/s13205-017-0837-z.
Heaton, M.P., Smith, T.P.L., Freking, B.A., Workman, A.M., Bennett, G.L., Carnahan, J.K., Kalbfleisch, T.S. :
Using sheep genomes from diverse U.S. breeds to identify missense variants in genes affecting fecundity. F1000Res 6:1303, 2017. Pubmed reference: 28928950. DOI: 10.12688/f1000research.12216.1.
2016 Bravo, S., Larama, G., Paz, E., Inostroza, K., Montaldo, H.H., Sepúlveda, N. :
Polymorphism of the GDF9 gene associated with litter size in Araucana creole sheep. Anim Genet 47:390-1, 2016. Pubmed reference: 27110683. DOI: 10.1111/age.12404.
Khodabakhshzadeh, R., Mohammadabadi, M.R., Esmailizadeh, A.K., Moradi Shahrebabak, H., Bordbar, F., Ansari Namin, S. :
Identification of point mutations in exon 2 of GDF9 gene in Kermani sheep. Pol J Vet Sci 19:281-9, 2016. Pubmed reference: 27487501. DOI: 10.1515/pjvs-2016-0035.
2015 Paz, E., Quiñones, J., Bravo, S., Montaldo, H.H., Sepúlveda, N. :
Genotyping of BMPR1B, BMP15 and GDF9 genes in Chilean sheep breeds and association with prolificacy. Anim Genet 46:98-9, 2015. Pubmed reference: 25530177. DOI: 10.1111/age.12254.
2014 Mullen, M.P., Hanrahan, J.P. :
Direct evidence on the contribution of a missense mutation in GDF9 to variation in ovulation rate of Finnsheep. PLoS One 9:e95251, 2014. Pubmed reference: 24751660. DOI: 10.1371/journal.pone.0095251.
Souza, C.J., McNeilly, A.S., Benavides, M.V., Melo, E.O., Moraes, J.C. :
Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes. Anim Genet 45:732-9, 2014. Pubmed reference: 25039891. DOI: 10.1111/age.12190.
2013 Farhadi, A., Genualdo, V., Perucatti, A., Hafezian, S.H., Rahimi-Mianji, G., De Lorenzi, L., Parma, P., Iannuzzi, L., Iannuzzi, A. :
Comparative FISH mapping of BMPR1B, BMP15 and GDF9 fecundity genes on cattle, river buffalo, sheep and goat chromosomes. J Genet 92:595-7, 2013. Pubmed reference: 24371182. DOI: 10.1007/s12041-013-0301-8.
Juengel, J.L., Davis, G.H., McNatty, K.P. :
Using sheep lines with mutations in single genes to better understand ovarian function. Reproduction 146:R111-23, 2013. Pubmed reference: 23801782. DOI: 10.1530/REP-12-0509.
Mullen, M.P., Hanrahan, J.P., Howard, D.J., Powell, R. :
Investigation of prolific sheep from UK and Ireland for evidence on origin of the mutations in BMP15 (FecX(G), FecX(B)) and GDF9 (FecG(H)) in Belclare and Cambridge sheep. PLoS One 8:e53172, 2013. Pubmed reference: 23301039. DOI: 10.1371/journal.pone.0053172.
Shafieiyan, Z., Mohammadi, G., Jolodarzadeh, A., Amiri, S. :
No mutations of FecB and FecG(H) in Iranian Lory sheep. Vet Res Forum 4:265-8, 2013. Pubmed reference: 25568682.
Våge, D.I., Husdal, M., Kent, M.P., Klemetsdal, G., Boman, I.A. :
A missense mutation in growth differentiation factor 9 (GDF9) is strongly associated with litter size in sheep. BMC Genet 14:1, 2013. Pubmed reference: 23280002. DOI: 10.1186/1471-2156-14-1.
Zuo, B., Qian, H., Wang, Z., Wang, X., Nisa, N., Bayier, A., Ying, S., Hu, X., Gong, C., Guo, Z., Wang, F. :
A Study on BMPR-IB Genes of Bayanbulak Sheep. Asian-Australas J Anim Sci 26:36-42, 2013. Pubmed reference: 25049703. DOI: 10.5713/ajas.2012.12238.
2012 Eghbalsaied, S., Ghaedi, K., Shahmoradi, S., Pirestani, A., Amini, H., Saiedi, T., Nicol, L., McNeilly, A. :
Presence of SNPs in GDF9 mRNA of Iranian Afshari Sheep. Int J Fertil Steril 5:225-30, 2012. Pubmed reference: 25210607.
2011 Chu, M.X., Yang, J., Feng, T., Cao, G.L., Fang, L., Di, R., Huang, D.W., Tang, Q.Q., Ma, Y.H., Li, K., Li, N. :
GDF9 as a candidate gene for prolificacy of Small Tail Han sheep. Mol Biol Rep 38:5199-204, 2011. Pubmed reference: 21184179. DOI: 10.1007/s11033-010-0670-5.
Javanmard, A., Azadzadeh, N., Esmailizadeh, A.K. :
Mutations in bone morphogenetic protein 15 and growth differentiation factor 9 genes are associated with increased litter size in fat-tailed sheep breeds. Vet Res Commun 35:157-67, 2011. Pubmed reference: 21327517. DOI: 10.1007/s11259-011-9467-9.
Roy, J., Polley, S., De, S., Mukherjee, A., Batabyal, S., Pan, S., Brahma, B., Datta, T.K., Goswami, S.L. :
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2002 Walling, G.A., Bishop, S.C., Pong-Wong, R., Gittus, G., Russel, A.J.F., Rhind, S.M. :
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