Characteristics of romanov breed locus bmp-15, responsible for prolificacy of the sheep

The article deals with the actual problem, the diagnostics of the prolificacy gene in sheep of the Romanov breed. The new method for the diagnostics of the polymorphic gene of the bone morphogenetic protein 15 (BMP-15), which causes the multiple pregnancy in the Romanov sheep, has been proposed based on the carried out surveys. The frequencies of occurrence of the normal (wild type) and mutant alleles responsible for the multiple pregnancy-related locus and the genotypes in the sheep are present. The economic indicators including the numbers of newborn lambs, the lambs at winning, and the dry and culled ewes were recorded with taking into consideration the genotypes of the BMP-15 locus. The relationships between the frequency of occurrence and the number of the produced posterity and between the dry and culled Romanov ewes were ascertained. It was proved that the highest percentage of the lamb output at birth to weaning was typical for the ewes homozygous (MM) for a mutant allele. The animals referred to as heterozygous genotypes (WM) appeared to be in the second position. With respect to the wild genotype, the highest percentage of the culled and dry ewes was recorded in the carriers of the WW homozygote. The obtained results allow us to conclude that the genotype frequency at the BMP-15 locus should be taken into account while estimating the fertility of the ewes. Therefore, the further researches into the determined phenomena in the Romanov sheep are required to improve this item, since the multi-fetal pregnancy is recorded in some ewes of group WW.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.

10.21203/rs.3.rs-54801/v3 ◽

2020 ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Abstract Background: Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts. Results: A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10 -43 ). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 ( BMP15 , Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10 -83 ) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth. Conclusion: Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs

BMC Genomics ◽

10.1186/s12864-020-07343-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Abstract Background Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts. Results A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10− 43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (BMP15; Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10-83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth. Conclusion Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs

10.1101/2020.08.03.222521 ◽

2020 ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

AbstractBackgroundAtypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts.ResultsA case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10-43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10-83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth.ConclusionOur results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.

10.21203/rs.3.rs-54801/v2 ◽

2020 ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Abstract Background: Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts.Results: A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10-43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (BMP15; Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10-83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth.Conclusion: Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.

10.21203/rs.3.rs-54801/v4 ◽

2020 ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Abstract Background Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts.Results A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10-43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (BMP15; Sscrofa11.1_X:g.44618787C>T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41±0.02 (P=4.5 × 10-83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth.Conclusion Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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Gonadotrophin-responsiveness of granulosa cells from bone morphogenetic protein 15 heterozygous mutant sheep

Reproduction ◽

10.1530/rep-09-0154 ◽

2009 ◽

Vol 138 (3) ◽

pp. 545-551 ◽

Cited By ~ 26

Author(s):

Kenneth P McNatty ◽

Derek A Heath ◽

Norma L Hudson ◽

Stan Lun ◽

Jennifer L Juengel ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Granulosa Cells ◽

Antral Follicle ◽

Human Chorionic Gonadotrophin ◽

Ovulation Rate ◽

Wild Type ◽

Binding Characteristics ◽

Enhanced Sensitivity ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

The aim of this study was to test the hypothesis that the higher ovulation-rate in ewes heterozygous for a mutation in bone morphogenetic protein 15 (BMP15; FecXI; otherwise known as Inverdale or I+ ewes) is due to granulosa cells developing an earlier responsiveness to LH, but not FSH. To address this hypothesis, granulosa cells were recovered from every individual nonatretic antral follicle (>2.5 mm diameter) from I+ and wild-type (++) ewes during anoestrus and the luteal and follicular phases and tested for their responsiveness to FSH and human chorionic gonadotrophin (hCG; a surrogate for LH). For the FSH receptor (FSHR) binding study, granulosa cells were harvested in three separate batches from all antral follicles (≥2.5 mm diameter) from I+ and ++ ewes. Using a highly-purified ovine FSH preparation, no evidence was found to suggest that I+ ewes have a higher ovulation-rate due to enhanced sensitivity of granulosa cells to FSH with respect to cAMP responsiveness or to their FSHR binding characteristics (equilibrium Kd or Bmax). By contrast, a significantly higher proportion of follicles from I+ ewes contained granulosa cells responsive to hCG. The higher proportion was due to cells from more small follicles (i.e. >2.5–4.5 mm diameter) developing a response to hCG. It is concluded that the mutation in the BMP15 gene in I+ ewes leads to an earlier acquisition of LH responsiveness by granulosa cells in a greater proportion of follicles and this accounts for the small but significantly higher ovulation-rate in these animals.

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A nonsense mutation of bone morphogenetic protein-15 (BMP15) causes both infertility and increased litter size in pigs.

10.21203/rs.3.rs-54801/v1 ◽

2020 ◽

Author(s):

Gabriele Flossmann ◽

Christine Wurmser ◽

Hubert Pausch ◽

Amabel Tenghe ◽

Jörg Dodenhoff ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Litter Size ◽

Nonsense Mutation ◽

Mutant Allele ◽

Breeding Population ◽

Dependent Manner ◽

Lean Meat ◽

Genetic Causes ◽

Morphogenetic Protein ◽

Bone Morphogenetic Protein 15

Abstract Background: Atypical external genitalia are often a sign of reproductive organ pathologies and infertility with both environmental or genetic causes, including karyotypic abnormalities. Genome-wide association studies (GWAS) provide a means for identifying chromosomal regions harboring deleterious DNA-variants causing such phenotypes. We performed a GWAS to unravel the causes of incidental cases of atypically small vulvae in German Landrace gilts.Results: A case-control GWAS involving Illumina porcine SNP60 BeadChip-called genotypes of 17 gilts with atypically small vulvae and 1,818 control animals (fertile German Landrace sows) identified a significantly associated region on the X-chromosome (P = 8.81 × 10− 43). Inspection of whole-genome sequencing data in the critical area allowed us to pinpoint a likely causal variant in the form of a nonsense mutation of bone morphogenetic protein-15 (Sscrofa11.1_X:g.44618787C > T, BMP15:p.R212X). The mutant allele occurs at a frequency of 6.2% in the German Landrace breeding population. Homozygous gilts exhibit underdeveloped, most likely not functional ovaries and are not fertile. Male carriers do not seem to manifest defects. Heterozygous sows produce 0.41 ± 0.02 (P = 4.5 × 10− 83) piglets more than wildtype animals. However, the mutant allele’s positive effect on litter size accompanies a negative impact on lean meat growth.Conclusion: Our results provide an example for the power of GWAS in identifying the genetic causes of a fuzzy phenotype and add to the list of natural deleterious BMP15 mutations that affect fertility in a dosage-dependent manner, the first time in a poly-ovulatory species. We advise eradicating the mutant allele from the German Landrace breeding population since the adverse effects on the lean meat growth outweigh the larger litter size in heterozygous sows.

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Expression Profiles of the Progesterone Receptor, Cyclooxygenase-2, Growth Differentiation Factor 9, and Bone Morphogenetic Protein 15 Transcripts in the Canine Oviducts during the Oestrous Cycle

Animals ◽

10.3390/ani11020454 ◽

2021 ◽

Vol 11 (2) ◽

pp. 454

Author(s):

Jaime Palomino ◽

Javiera Flores ◽

Georges Ramirez ◽

Victor H. Parraguez ◽

Monica De los Reyes

Keyword(s):

Gene Expression ◽

Bone Morphogenetic Protein ◽

Cyclooxygenase 2 ◽

Oestrous Cycle ◽

Progesterone Concentration ◽

Plasma Progesterone ◽

Morphogenetic Protein ◽

Growth Differentiation Factor 9 ◽

Bone Morphogenetic Protein 15 ◽

Cox 2

The gene expression in the canine oviduct, where oocyte maturation, fertilization, and early embryonic development occur, is still elusive. This study determined the oviductal expression of (PR), cyclooxygenase-2 (COX-2), growth differentiation factor 9 (GDF-9), and bone morphogenetic protein 15 (BMP-15) during the canine oestrous cycle. Samples were collected from bitches at anoestrus (9), proestrus (7), oestrus (8), and dioestrus (11), after routine ovariohysterectomy and the ovarian surface structures and plasma progesterone concentration evaluated the physiological status of each donor. The oviductal cells were isolated and pooled. Total RNA was isolated, and gene expression was assessed by qPCR followed by analysis using the t-test and ANOVA. The PR mRNA increased (P < 0.05) from the anoestrus to dioestrus with the plasma progesterone concentration (r = 0.8). COX-2 mRNA expression was low in the anoestrus and proestrus, and negligible in the oestrus, while it was around 10-fold higher (P < 0.05) in the dioestrus. The GDF-9 mRNA was expressed during all phases of the oestrous cycle and was most abundant (P < 0.05) during oestrus phase. The BMP-15 mRNA decreased (P < 0.05) in the anoestrus and proestrus phases. Thus, the transcripts were differentially expressed in a stage-dependent manner, suggesting the importance of oestrous cycle regulation for successful reproduction in dogs.

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The Identification of Mutation in BMP15 Gene Associated with Litter Size in Xinjiang Cele Black Sheep

Animals ◽

10.3390/ani11030668 ◽

2021 ◽

Vol 11 (3) ◽

pp. 668

Author(s):

Zhi-gang Niu ◽

Jin Qin ◽

Yao Jiang ◽

Xiang-Dong Ding ◽

Yu-gong Ding ◽

...

Keyword(s):

Sequence Analysis ◽

Litter Size ◽

Base Change ◽

Wild Type ◽

Wild Genotype ◽

Exon 2 ◽

Black Sheep ◽

Morphogenetic Protein ◽

Gene Sequence Analysis ◽

Exon 1

The Bone Morphogenetic Protein 15 (BMP15) gene is known to have multiple single-nucleotide polymorphism sites associated with sheep fecundity. This study used gene sequence analysis and mutation detection assays for BMP15 by using 205 blood samples of ewes with known lambing records. Sequence analysis showed that mutation B1 missed the CTT base in exon 1 at positions 28–30, leading to a leucine deletion in the BMP15 protein. Litter size of ewes differed significantly between BB and B+ genotypes of B1 (p < 0.05); however, the differences between wild genotype (++) and homozygous (BB) or wild genotype (++) and heterozygous (B+) were not significant (p > 0.05). Another mutation, T755C, is a T-to-C base change at position 755 of exon 2, resulting in leucine replacement by proline at this position of the BMP15 protein (p.L252P). Two genotypes were identified in the flock: heterozygous (E+) and wild-type genotype (++). Ewes with heterozygous (E+) p.L252P had significantly larger litter sizes than those with the wild-type genotype (p < 0.05). Comprehensive analysis suggests that p.L252P is a mutation that affects fecundity in Cele black sheep.

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