OMIA 002306-9940 : Fecundity, BMP15-related in Ovis aries

In other species: pig

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 300247 (gene) , 300510 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked

Considered a defect: no

Key variant known: yes

Species-specific description: For additional variants in the BMP15 gene that are associated with fecundity in sheep see the following entries: OMIA 001350-9940 Fecundity, Hanna, FecX(H); OMIA 002107-9940 Fecundity, Barbarine, FecX(Bar); OMIA 001357-9940 Fecundity, Lacaune, FecX(L); OMIA 001719-9940 Fecundity, Belclare, FecX(B); OMIA 001798-9940 Fecundity, Grivette, FecX(Gr); OMIA 001799-9940 Fecundity, Olkuska, FecX(O); OMIA 000384-9940 Fecundity, Galway, FecX(G); OMIA 001800-9940 Fecundity, Rasa Aragonesa, FecX(R); OMIA 000386-9940 Fecundity, Inverdale, FecX(I)

Markers: Chantepie et al. (2020): "A new single nucleotide polymorphism (OARX:50977717T > A, NC_019484) located on the X chromosome upstream of the BMP15 gene was evidenced to be highly associated with the prolificacy variability (P = 1.93E-11). The variant allele was called FecX N ... . In both NV [Noire du Velay] and BMC [Blanche du Massif Central], the FecX N allele frequency was estimated close to 0.10, and its effect on LS was estimated at +0.20 lamb per lambing at the heterozygous state. Homozygous FecX N carrier ewes were fertile with increased prolificacy in contrast to numerous mutations affecting BMP15. At the molecular level, FecX N was shown to decrease BMP15 promoter activity and supposed to impact BMP15 expression in the oocyte."

Calvo et al. (2020) “identified a novel polymorphism in exon 2 of BMP15 in 9 high prolific ewes by Sanger sequencing. This new mutation, called FecXRA, is a SNP (Oar3.1_X: g. 50970948C > T; NM_001114767.1: c.1172C > T) that produces an amino acid substitution (ENSOART00000010201: p.T400I) that is predicted to be deleterious and to alter the predicted secondary structure of the mature protein. … an association study was performed to validate and quantify the effects of the FecXGR and FecXRA alleles. Significant increased prolificacy of 0.52 ± 0.05, 0.42 ± 0.05 and 0.32 ± 0.01 were found when comparing FecXGR, FecXRA and FecXR heterozygous ewes to wild type homozygous ones. These effects are of the same order of magnitude as the effect of most of other known major genes for prolificacy. Only significant differences between FecXGR and FecXR were found among the three alleles associated with increased prolificacy. However, we cannot confirm the effect of the FecXRA allele at homozygous state because we did not find any homozygous ewes. These results confirm that these three alleles in the BMP15 gene that affect prolificacy co-segregate in Rasa aragonesa sheep.”

Çelikeloğlu et al. (2021) “polymorphisms in genes affecting litter size ... were detected in 60 uniparous and 60 multiparous ewes from Ramlıç and Dağlıç breeds. … PCR and DNA sequencing analyses were conducted, and 36, 4, and 11 SNPs in Ramlıç and 40, 3, and 11 SNPs in Dağlıç were detected in BMPR1B, BMP15, and GDF9 genes, respectively. A total of 16 SNPs in Ramlıç and 10 SNPs in Dağlıç breeds for three genes were found to be significant (P<0.05). The resulting analyses showed that four SNPs (g.49496G>A, c.1658A>C, c.2037C>T, c.2053C>T) of the BMPR1B gene and one deletion mutation (c.28_30delCTT) in the BMP15 gene of the Ramlıç breed as well as five SNPs (c.1487C>A, c.2492C>T, c.2523G>A, c.2880A>G, and c.2763G>A) of the BMPR1B gene of the Dağlıç breed have significant positive regression coefficients in the desired direction of the rare allele. The observed mutations have potential to be used as genetic markers in the selection of prolific animals for both breeds.”

Najafabadi et al. (2021) report an association between litter size and the variant c.31_33del, p.(L11del) in a small number of composite sheep in New Zealand. This variant was initially identified by Galloway et al. (2000). Najafabadi et al. (2021) acknowledge that analysis in a larger population is required to confirm these results, particularly as most other studies that analysed this variant did not identify an association with fecundity.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
BMP15 bone morphogenetic protein 15 Ovis aries X NC_056080.1 (54290315..54283635) BMP15 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
Rasa Aragonesa Fecundity BMP15 FecX^RA missense Oar3.1 X g.50970948C>T c.1172C>T p.(T400I) protein position based on ENSOART00000010201 2020 31927415
Blanche du Massif Central Noire du Velay Fecundity BMP15 FecX^N regulatory Oar3.1 X g.50977717T>A 2020 32636872

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.
2021 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.
Najafabadi, H.A., Khansefid, M., Mahmoud, G.G., Haruna, I.L., Zhou, H., Hickford, J.G.H. :
Identification of sequence variation in the oocyte-derived bone morphogenetic protein 15 (BMP15) gene (BMP15) associated with litter size in New Zealand sheep (Ovis aries) breeds. Mol Biol Rep :, 2021. Pubmed reference: 34379287. DOI: 10.1007/s11033-021-06627-z.
2020 Calvo, J.H., Chantepie, L., Serrano, M., Sarto, M.P., Iguacel, L.P., Jiménez, M.Á., Alabart, J.L., Folch, J., Fabre, S., Lahoz, B. :
A new allele in the BMP15 gene (FecXRA) that affects prolificacy co-segregates with FecXR and FecXGR in Rasa aragonesa sheep. Theriogenology 144:107-111, 2020. Pubmed reference: 31927415. DOI: 10.1016/j.theriogenology.2020.01.010.
Chantepie, L., Bodin, L., Sarry, J., Woloszyn, F., Plisson-Petit, F., Ruesche, J., Drouilhet, L., Fabre, S. :
Genome-wide identification of a regulatory mutation in BMP15 controlling prolificacy in sheep. Front Genet 11:585, 2020. Pubmed reference: 32636872. DOI: 10.3389/fgene.2020.00585.
2018 Amini, H.-R., Ajaki, A., Majid Farahi, M., Mitra Heidari, M., Ahmad Pirali, A., Forouzanfar, M., Eghbalsaied, S. :
The novel T755C mutation in BMP15 is associated with the litter size of Iranian Afshari, Ghezel, and Shal breeds. Archiv fuer Tierzucht 61:153-160, 2018. DOI: DOI:10.5194/aab-61-153-2018.
Zhou, S., Yu, H., Zhao, X., Cai, B., Ding, Q., Huang, Y., Li, Y., Li, Y., Niu, Y., Lei, A., Kou, Q., Huang, X., Petersen, B., Ma, B., Chen, Y., Wang, X. :
Generation of gene-edited sheep with a defined Booroola fecundity gene (FecB<sup>B</sup>) mutation in bone morphogenetic protein receptor type 1B (BMPR1B) via clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9. Reprod Fertil Dev 30:1616-1621, 2018. Pubmed reference: 31039970. DOI: 10.1071/RD18086.
2013 Demars, J., Fabre, S., Sarry, J., Rossetti, R., Gilbert, H., Persani, L., Tosser-Klopp, G., Mulsant, P., Nowak, Z., Drobik, W., Martyniuk, E., Bodin, L. :
Genome-wide association studies identify two novel BMP15 mutations responsible for an atypical hyperprolificacy phenotype in sheep. PLoS Genet 9:e1003482, 2013. Pubmed reference: 23637641. DOI: 10.1371/journal.pgen.1003482.
2009 Drouilhet, L., Lecerf, F., Bodin, L., Fabre, S., Mulsant, P. :
Fine mapping of the FecL locus influencing prolificacy in Lacaune sheep. Anim Genet 40:804-12, 2009. Pubmed reference: 19466934. DOI: 10.1111/j.1365-2052.2009.01919.x.
2008 Martinez-Royo, A., Jurado, J.J., Smulders, J.P., Martí, J.I., Alabart, J.L., Roche, A., Fantova, E., Bodin, L., Mulsant, P., Serrano, M., Folch, J., Calvo, J.H. :
A deletion in the bone morphogenetic protein 15 gene causes sterility and increased prolificacy in Rasa Aragonesa sheep. Anim Genet 39:294-7, 2008. Pubmed reference: 18355397. DOI: 10.1111/j.1365-2052.2008.01707.x.
2007 Bodin, L., Di Pasquale, E., Fabre, S., Bontoux, M., Monget, P., Persani, L., Mulsant, P. :
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, 2007. Pubmed reference: 17038554. DOI: 10.1210/en.2006-0764.
Chu, MX., Liu, ZH., Jiao, CL., He, YQ., Fang, L., Ye, SC., Chen, GH., Wang, JY. :
Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small Tailed Han sheep (Ovis aries). J Anim Sci 85:598-603, 2007. Pubmed reference: 17040942. DOI: 10.2527/jas.2006-324.
2005 Chu, MX., Sang, LH., Wang, JY., Fang, L., Ye, SC. :
[Study on BMP15 and GDF9 as candidate genes for prolificacy of Small Tail Han sheep] Yi Chuan Xue Bao 32:38-45, 2005. Pubmed reference: 15715436.
Moore, RK., Shimasaki, S. :
Molecular biology and physiological role of the oocyte factor, BMP-15. Mol Cell Endocrinol 234:67-73, 2005. Pubmed reference: 15836954. DOI: 10.1016/j.mce.2004.10.012.
2004 Hanrahan, JP., Gregan, SM., Mulsant, P., Mullen, M., Davis, GH., Powell, R., Galloway, SM. :
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 70:900-9, 2004. Pubmed reference: 14627550. DOI: 10.1095/biolreprod.103.023093.
2002 Juengel, J.L., Hudson, N.L., Heath, D.A., Smith, P., Reader, K.L., Lawrence, S.B., O'Connell, A.R., Laitinen, M.P., Cranfield, M., Groome, N.P., Ritvos, O., McNatty, K.P. :
Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod 67:1777-89, 2002. Pubmed reference: 12444053. DOI: 10.1095/biolreprod.102.007146.
2001 Montgomery, G.W., Galloway, S.M., Davis, G.H., McNatty, K.P. :
Genes controlling ovulation rate in sheep Reproduction 121:843-852, 2001. Pubmed reference: 11373170.
2000 Galloway, S.M., McNatty, K.P., Cambridge, L.M., Laitinen, M.P.E., Juengel, J.L., Jokiranta, T.S., McLaren, R.J., Luiro, K., Dodds, K.G., Montgomery, G.W., Beattie, A.E., Davis, G.H., Ritvos, O. :
Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner Nature Genetics 25:279-283, 2000. Pubmed reference: 10888873. DOI: 10.1038/77033.

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