1. bookVolume 21 (2021): Issue 1 (January 2021)
Journal Details
License
Format
Journal
eISSN
2300-8733
First Published
25 Nov 2011
Publication timeframe
4 times per year
Languages
English
access type Open Access

Frequency of BMP15 and GDF9 mutations increasing litter size and their phenotypic effects in Olkuska sheep population

Published Online: 29 Jan 2021
Volume & Issue: Volume 21 (2021) - Issue 1 (January 2021)
Page range: 89 - 108
Received: 13 Nov 2019
Accepted: 14 May 2020
Journal Details
License
Format
Journal
eISSN
2300-8733
First Published
25 Nov 2011
Publication timeframe
4 times per year
Languages
English
Abstract

Two mutations affecting the ovulation rate and litter size are segregating in Olkuska sheep population, FecXO in the BMP15 gene, and the G7 site mutation in GDF9 gene. Homozygous carriers of both mutations are hyperprolific, contrary to the sterility observed in homozygous carriers of most other BMP15 and GDF9 mutations. The objective of this study was to assess frequency and phenotypic effects of both mutations. Blood samples were obtained from 740 individuals, 111 rams and 629 ewes, out of which 91 rams and 561 ewes were successfully genotyped for the BMP15 and GDF9 loci. The reproductive performance included a number of lambs born/born alive and a number of lambs reared until 60 days of age, and for a subset of ewe ovulation rates. The study proved a high frequency of the FecXO mutation in two flocks that have been selected for many years for increased litter size (0.7–1.0 in breeding ewes and rams respectively), and a moderate frequency in another 19 private flocks (0.4–0.5). The frequency of the GDF9 mutation was low, with only 50 sheep out of 312 genotyped being carriers of the GDF9/G7 mutation, including three homozygous carriers. The FecXO mutation in the BMP15 had a significant effect on both litter size and the ovulation rate. The single copy in heterozygous carriers increased litter size by 0.255 (0.063), while the effect of two copies in homozygous genotypes was +0.874 (0.081) lambs born. Due to the low frequency of the GDF9 mutation, it can only be preliminarily concluded that litter size has been increased in double carriers of both the BM15 and GDF9 mutation, which may suggest their additive interaction. The positive effect of both mutations supports their direct use in selection programmes.

Keywords

Amini H.R., Ajaki A., Farahi M., Heidari M., Pirali A., Forouzanfar M., Eghbalsaied S. (2018). The novel T755C mutation in BMP15 is associated with the litter size of Iranian Afshari, Ghezel, and Shal breeds. Arch. Anim. Breed., 61: 153–160.Search in Google Scholar

Bates D., Machler M., Bolker B.M., Walker S.C. (2015). Fitting linear mixed-effects models using lme4. J. Stat. Softw., 67: 1–48.Search in Google Scholar

Bodin L., Di Pasquale E., Fabre S., Bontoux M., Monget P., Persani L., Mulsant P. (2007). A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology, 148: 393–400.Search in Google Scholar

Bravo S., Larama G., Paz E., Inostroza K., Montaldo H., Sepulveda N. (2016). Polymorphism of the GDF9 gene associated with litter size in Araucana creole sheep. Anim. Genet., 47: 390–391.Search in Google Scholar

Chantepie L., Bodin L., Sarry J., Woloszyn F., Ruesche J., Drouilhet L., Fabre S. (2018). Presence of causative mutations affecting prolificacy in the Noire du Velay and Mouton Vendéen sheep breeds. Livest. Sci., 216: 44–50.Search in Google Scholar

Davis G.H. (2005). Major genes affecting ovulation rate in sheep. Genet. Sel. Evol., 37: 11–23.Search in Google Scholar

Davis G.H., Galloway S.M., Ross I.K., Gregan S.M., Ward J., Nimbkar B.V., Ghalsasi P.M., Nimbkar C., Gray G.D., Subandriyo, Inounu I., Tiesnamurti B., Martyniuk E., Eythorsdottir E., Mulsant P., Lecerf F., Hanrahan J.P., Bradford G.E., Wilson T. (2002). DNA tests in prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation. Biol. Reprod., 66: 1869–1874.Search in Google Scholar

Demars J., Fabre F., Sarry J., Rossetti R., Gilbert H., Persani L., Tosser-Klopp G., Mulsant P., Nowak Z., Drobik W., Martyniuk E., Bodin L. (2013). Genome-wide association studies identify two novel bmp15 mutations responsible for an atypical hyperprolificacy phenotype in sheep. PloS Genet., 9 (4): e1003482.Search in Google Scholar

Dolebo A.T., Khayatzadeh N., Melesse A., Wragg D., Rekik M., Haile A., Rischkowsky B., Rothschild M.F., Mwacharo J.M. (2019). Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries). Mammalian Genome. 30: 339–352.Search in Google Scholar

Drobik W., Martyniuk E. (2014). Factors affecting prolificacy and lambs rearing results in Olkuska sheep population. Ann. Warsaw Univ. Life Sci. - SGGW, Anim. Sci. 53: 85–94.Search in Google Scholar

Drobik W., Martyniuk E. (2016). Inbreeding and its impact on the prolific Polish Olkuska sheep population. Small Rumin. Res., 137: 28–33.Search in Google Scholar

Drouilhet L., Mansanet C., Sarry J., Tabet K., Bardou P., Woloszyn F., Lluch J., Harichaux G., Viguié C., Monniaux D., Bodin L., Mulsant P., Fabre S. (2013). The highly prolific phenotype of Lacaune sheep is associated with an ectopic expression of the B4GALNT2 gene within the ovary. PloS Genet, 9 (9): e1003809.Search in Google Scholar

Eghbalsaied S., Khorasgani F.R., Amini H-R., Farahi M., Davari M., Pirali A., Pourali S., Vatankhah M., Rostami M., Atashi H. (2017). Variant GDF9 mRNA is likely not the main cause of larger litter size in Iranian Lori-Bakhtyari, Shal, Ghezel, and Afshari sheep breeds. Arch. Anim. Breed., 60: 119–129.Search in Google Scholar

Foroughinia G., Fazileh A., Eghbalsaied S. (2017). Expression of genes involved in BMP and estrogen signaling and AMPK production can be important factors affecting total number of antral follicles in ewes. Theriogenology, 91: 36–43.Search in Google Scholar

Galloway S.M., Mc Natty K.P., Cambridge L.M., Laitinen M.P., Juengel J.L., Jokiranta T.S., Mc Laren R.J., Luiro K., Dodds K.G., Montgomery G.W., Beattie A.E., Davis G.H., Ritvos O. (2000). Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nature Genet., 25: 279–283.Search in Google Scholar

Gorlov I.F., Kolosov Y.A., Shirokova N.V., Getmantseva L.V., Slozhenkina M.I., Mosolova N.I., Bakoev N.F., Leonova M.A., Kolosov A.Y., Zlobina E.Y. (2017). GDF9 gene polymorphism and its association with litter size in two Russian sheep breeds. Rendiconti Lincei. Scienze Fisiche e Naturali, 29: 61–66.Search in Google Scholar

Hanrahan J.P., Gregan S.M., Mulsant P., Mullen M., Davis G.H., Powell R., Galloway S.M. (2004). Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol. Reprod., 70: 900–909.Search in Google Scholar

Hua G.H., Yang L.G. (2009). Biological and economic consequences of the FecB mutation in Chinese breeds of sheep. In: Use of the FecB (Booroola) gene in sheep-breeding programs, Walkden-Brown S.W., van der Werf J.H.J., Nimbkar C., Gupta V.S. (eds). Proc. Helen Newton Turner Memorial International Workshop held in Pune. Maharashtra, India, 10–12.11.2008. ACIAR Proceedings No. 133. Australian Centre for International Agricultural Research, Canberra, pp 238. http://aciar.gov.au/files/node/11617/ACIAR_PR133(online).pdfSearch in Google Scholar

Kaczor U. (2017). Genes involved in litter size in Olkuska sheep. In: Genetic polymorphisms. Chapter 12. INTECH: World’s largest Science, Technology & Medicine Open Access book publisher, pp. 251–270. http://dx.doi.org/10.5772/intechopen.6920510.5772/intechopen.69205Search in Google Scholar

Korczynski T. (2007). Personal information: http://www.fao.org/ag/againfo/programmes/en/genetics/documents/Interlaken/fv_poland_1.pdfSearch in Google Scholar

Lassoued N., Benkhlil Z., Woloszyn F., Rejeb A., Aouina M., Rekik M., Fabre S., Bedhiaf-Romdhani S. (2017). FecXBar a novel BMP15 mutation responsible for prolificacy and female sterility in Tunisian Barbarine sheep. BMC Genet., 18: 43.Search in Google Scholar

Martin P., Raoul J., Bolin L. (2014). Effects of the FecL major gene in the Lacaune meat sheep population. Genet. Sel. Evol., 46: 48.Search in Google Scholar

Martinez-Royo A., Jurado J.J., Smulders J.P., Marti J.I., Alabart J.L., Roche A., Fantova E., Bodin L., Mulsant P., Serrano M., Folch J., Calvo J.H. (2008). A deletion in the bone morphogenetic protein 15 gene causes sterility and increased prolificacy in Rasa Aragonesa sheep. Anim. Genet., 39: 294–297.Search in Google Scholar

Monteagudo L.V., Ponz R., Tejedor M.T., Lavina A., Sierra I. (2009). A 17 bp deletion in the Bone Morphogenetic Protein 15 (BMP15) gene is associated to increased prolificacy in the Rasa Aragonesa sheep breed. Anim. Reprod. Sci., 110: 139–146.Search in Google Scholar

Mulsant P., Lecerf F., Fabre S., Schibler L., Monget P., Lanneluc I., Pisselet C., Riquet J., Monniaux D., Callebaut I., Cribiu E., Thimonier J., Teyssier J., Bodin L., Cognié Y., Chitour N., Elsen J.M. (2001). Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. P. Natl. Acad. Sci. USA, 98: 5104–5109.Search in Google Scholar

Nadri S., Zamani P., Ahmadi A. (2016). Novel mutation in exon 1 of the BMP15 gene and its association with reproduction traits in sheep. Anim. Biotechnol., 27: 256–261.Search in Google Scholar

Nicol L., Bishop S.C., Pong-Wong R., Bendixen C., Holm L.E., Rhind S.M., Mc Neilly A.S. (2009). Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction, 138: 921–933.Search in Google Scholar

Paz E., Quiñones J., Bravo S., Montaldo H.H., Sepúlveda N. (2014). Genotyping of BMPR1B,BMP15 and GDF9 genes in Chilean sheep breeds and association with prolificacy. Anim. Genet., 46: 98–99.Search in Google Scholar

Silva B.D., Castro E.A., Souza C.J., Paiva S.R., Sartori R., Franco M.M., Azevedo H.C., Silva T.A., Vieira A.M., Neves J.P., Melo E.O. (2011). A new polymorphism in the Growth and Differentiation Factor 9 (GDF9) gene is associated with increased ovulation rate and prolificacy in homozygous sheep. Anim. Genet., 42: 89–92.Search in Google Scholar

Souza C.J., Mac Dougall C., Campbell B.K., Mc Neilly A.S., Baird D.T. (2001). The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. J. Endocrinol., 169: R1–6.Search in Google Scholar

Souza C.J.H., Mc Neilly A.S., Benavides M.V., Melo E.O., Moraes J.C.F. (2014). 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: 732–739.Search in Google Scholar

Våge D.I., Husdal M., Matthew P.K., Klemetsdal G., Boman I.A. (2013). A missense mutation in growth differentiation factor 9 (GDF9) is strongly associated with litter size in sheep. BMC Genet., 14: 1.Search in Google Scholar

Wilson T., Wu X.Y., Juengel J.L., Ross I.K., Lumsden J.M., Lord E.A., Dodds K.G., Walling G.A., Mc Ewan J.C., O’Connell A.R., Mc Natty K.P., Montgomery G.W. (2001). Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol. Reprod., 64: 1225–1235.Search in Google Scholar

Zamani P., Nadri S., Saffaripour R., Ahmadi A., Dashti F., Abdoli R. (2015). A new mutation in exon 2 of the bone morphogenetic protein 15 gene is associated with increase in prolificacy of Mehraban and Lori sheep. Trop. Anim. Health Pro., 47: 855–860.Search in Google Scholar

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