Direct Evidence on the Contribution of a Missense Mutation in GDF9 to Variation in Ovulation Rate of Finnsheep

The Finnish Landrace (Finnsheep) is a well known high-prolificacy sheep breed and has been used in many countries as a source of genetic material to increase fecundity of local breeds. Analyses to date have indicated that mutations with a large effect on ovulation rate are not responsible for the exceptional prolificacy of Finnsheep. The objectives of this study were to ascertain if: 1) any of 12 known mutations with large effects on ovulation rate in sheep, or 2) any other DNA sequence variants within the candidate genes GDF9 and BMP15 are implicated in the high prolificacy of the Finnish Landrace breed; using material from lines developed by divergent selection on ovulation rate. Genotyping results showed that none of 12 known mutations (FecB^B, FecX^B, FecX^G, FecX^GR, FecX^H, FecX^I, FecX^L, FecX^O, FecX^R, FecG^E, FecG^H, or FecG^T) were present in a sample of 108 Finnsheep and, thus, do not contribute to the exceptional prolificacy of the breed. However, DNA sequence analysis of GDF9 identified a previously known mutation, V371M, whose frequency differed significantly (P<0.001) between High and Low ovulation rate lines. While analysis of ovulation rate data for Finnsheep failed to establish a significant association between this trait and V371M, analysis of data on Belclare sheep revealed a significant association between V371M and ovulation rate (P<0.01). Ewes that were heterozygous for V371M exhibited increased ovulation rate (+0.17, s.e. 0.080; P<0.05) compared to wild type and the effect was non-additive (ovulation rate of heterozygotes was significantly lower (P<0.01) than the mean of the homozygotes). This finding brings to 13 the number of mutations that have large effects on ovulation rate in sheep and to 5, including FecB^B, FecG^E, FecX^O and FecX^GR, the number of mutations within the TGFβ superfamily with a positive effect on prolificacy in the homozygous state.     

Hormonal relationships during the periovulatory period among ewe breeds known to differ in fertility after cervical artificial insemination with frozen thawed semen

Our previous work indicates that ewe breed differences in fertility following cervical AI with frozen-thawed semen are due to failure of normal sperm transport and/or early embryo development. Here we examined differences in hormone concentrations about the time of ovulation among more (Finnish Landrace and Belclare) and less (Suffolk and Texel) fertile ewes after AI with frozen thawed semen. In Experiment 1, oestradiol concentrations were measured in samples collected frequently from 12h before to 18h after the LH surge and progesterone was measured in samples collected from 9 to 27h after the LH surge in Suffolk (n=24), Texel (n=20) and Finnish Landrace (n=27) ewes. In Experiment 2, oestradiol concentrations were measured in samples collected frequently from 24h before to 6h after the LH surge and progesterone was measured in samples collected from 6h to 6 days after the LH surge in Suffolk (n=35) and Belclare (n=30) ewes. In Experiment 1, there was an effect of breed, time and their interaction (P<0.001) on oestradiol concentrations between -12 and +6h but only breed differences at +12 and +18h (P<0.01). Progesterone concentrations increased over time (P<0.001) and the rate of increase was significantly greater in Finnish Landrace than in the other two breeds. In Experiment 2, oestradiol concentrations were unaffected by breed. There was an interaction between breed and time with the rate of increase of progesterone being greater in Belclare than Suffolk ewes (P<0.001). In conclusion, differences in hormone concentrations in the periovulatory period are not consistent with ewe breed differences in fertility; however, we have showed that progesterone concentrations rise earlier in the more prolific breeds and suggest that this may explain reported ewe breed differences in embryo development.     

Repeatability of the duration of oestrus and breed differences in the relationship between druation of oestrus and ovulation rate of sheep.

The duration of oestrus and the time interval from removal of progestagen-impregnated pessaries to the onset and end of oestrus were examined in Texel, Finnish Landrace, Galway and Fingalway (Finnish Landrace X Galway) ewes. The differences among the breeds in the relationship between these variables and ovulation rate at the controlled oestrus were also investigated. Breed differences were significant for all traits except the interval from pessary withdrawal to the onset of oestrus. The relationship between ovulation rate and both the interval from pessary withdrawal to the onset of oestrus and the duration of oestrus differed significantly among the breeds. The repeatability of the duration of oestrus was significant for Texel and Rambouillet ewes (mean = 0.5) and for pooled data from ewe lambs of various breeds. It was concluded that, in view of the breed differences in the relationship between ovulation rate and duration of oestrus and other traits, generalizations should not be made from among-breed to within-breed relationships. The high repeatability for the duration of oestrus may mean substantial heritabilities for the physiological determinants of oestrus duration.     

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)

Belclare and Cambridge are prolific sheep breeds, the origins of which involved selecting ewes with exceptionally high litter size records from commercial flocks. The variation in ovulation rate in both breeds is consistent with segregation of a gene (or genes) with a large effect on this trait. Sterile ewes, due to a failure of normal ovarian follicle development, occur in both breeds. New naturally occurring mutations in genes for the oocyte-derived growth factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are described. These mutations are associated with increased ovulation rate in heterozygous carriers and sterility in homozygous carriers in both breeds. 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.     

Genome-Wide Association Studies Identify Two Novel BMP15 Mutations Responsible for an Atypical Hyperprolificacy Phenotype in Sheep

Some sheep breeds are naturally prolific, and they are very informative for the studies of reproductive genetics and physiology. Major genes increasing litter size (LS) and ovulation rate (OR) were suspected in the French Grivette and the Polish Olkuska sheep populations, respectively. To identify genetic variants responsible for the highly prolific phenotype in these two breeds, genome-wide association studies (GWAS) followed by complementary genetic and functional analyses were performed. Highly prolific ewes (cases) and normal prolific ewes (controls) from each breed were genotyped using the Illumina OvineSNP50 Genotyping Beadchip. In both populations, an X chromosome region, close to the BMP15 gene, harbored clusters of markers with suggestive evidence of association at significance levels between 1E⁻⁰⁵ and 1E⁻⁰⁷. The BMP15 candidate gene was then sequenced, and two novel non-conservative mutations called FecX^Gr and FecX^O were identified in the Grivette and Olkuska breeds, respectively. The two mutations were associated with the highly prolific phenotype (p_FecX^Gr = 5.98E⁻⁰⁶ and p_FecX^O = 2.55E⁻⁰⁸). Homozygous ewes for the mutated allele showed a significantly increased prolificacy (FecX^Gr/FecX^Gr, LS = 2.50±0.65 versus FecX⁺/FecX^Gr, LS = 1.93±0.42, p<1E⁻⁰³ and FecX^O/FecX^O, OR = 3.28±0.85 versus FecX⁺/FecX^O, OR = 2.02±0.47, p<1E⁻⁰³). Both mutations are located in very well conserved motifs of the protein and altered the BMP15 signaling activity in vitro using a BMP-responsive luciferase test in COV434 granulosa cells. Thus, we have identified two novel mutations in the BMP15 gene associated with increased LS and OR. Notably, homozygous FecX^Gr/FecX^Gr Grivette and homozygous FecX^O/FecX^O Olkuska ewes are hyperprolific in striking contrast with the sterility exhibited by all other known homozygous BMP15 mutations. Our results bring new insights into the key role played by the BMP15 protein in ovarian function and could contribute to a better understanding of the pathogenesis of women′s fertility disorders.     

Gonadotrophin secretion during the periovulatory period in Galway and Finnish Landrace ewes and Finnish Landrace ewes selected for high ovulation rate

Rates of ovulation differed significantly (P less than 0.01) among ewes of the different genetic lines. However, of the reproductive characteristics studied, only progesterone concentration at the height of luteal function, duration of oestrus, and interval from onset of oestrus to peak of the preovulatory gonadotrophin surge showed significant positive association with rate of ovulation. The pattern of secretion of LH during the periovulatory period did not differ in the Galway and Finnish Landrace breeds. The total amount of LH secreted during the preovulatory surge did not differ amongst lines. Similarly, no difference in the plasma concentration of LH at the height of the preovulatory surge was noted among Galway and reference Finnish Landrace lines. However, the concentration of LH at the height of the surge was significantly (P less than 0.05) reduced in the selected Finnish Landrace line. Plasma concentrations of FSH during the preovulatory period were significantly (P less than 0.05) elevated in the breed (Galway) with the lowest prolifcacy. When contrasted with either of the Finnish Landrace lines, the magnitudes of the preovulatory surge of FSH and the secondary surge of FSH were significantly greater (P less than 0.05) in Galway ewes. These results suggest that genetic difference in rate of ovulation among sheep breeds is not tightly coupled to quantitative differences in plasma concentration of gonadotrophic hormones during the periovulatory period.     

Effects of sire breed on ewe dystocia, lamb survival and weaned lamb output in hill sheep systems

A study was carried out on six hill farms, located in the main hill regions of Northern Ireland, over three breeding seasons to investigate the effect of sire breed on ewe dystocia, lamb survival and weaned lamb output. On each farm, groups of 26 to 40 purebred Scottish Blackface ewes (n = 3174) were crossed with Blackface, Swaledale, North Country Cheviot, Lleyn and Texel sires by natural service (year 1) and artificial insemination (years 2 and 3). Each of the mating groups was initially balanced for ewe age, live weight and condition score, and a total of 15 sires of each breed were used over the 3 years. In total, 2272 ewes were recorded at lambing, producing 3451 lambs, over the 3 years. Sire breed had a significant effect (P < 0.001) on lamb birth weight with Blackface and Swaledale the lowest and Texel the highest. The proportion of ewes with dystocia was higher with Texel sires compared with Lleyn, Swaledale and Blackface sires (P < 0.05). Ewes mated to Cheviot sires had more dystocia than those mated to Blackface and Swaledale sires (P < 0.05), while ewes mated to Lleyn sire breed had more dystocia (P < 0.05) than those mated to Blackface sire breed. Most of the incidence of dystocia was attributable to increased lamb birth weight (P < 0.001), and some to litter size (P < 0.05). Swaledale, Cheviot, Lleyn and Texel sire breeds increased the incidence of malpresentations (P < 0.05). Lamb live weight at weaning was higher with Texel- and Cheviot- and Lleyn-sired lambs compared with Blackface- and Swaledale-sired lambs (P < 0.01). The level of lamb mortality at birth was not affected by sire breed. However, lamb mortality at weaning was lower for Lleyn-sired lambs compared with the other lamb genotypes (P < 0.05). These results indicate that the use of sires from larger breeds, such as Lleyn and Texel, within the Blackface ewe flocks can increase lamb output, with no apparent detrimental effects on lamb mortality or ewe survival, but increased assistance at lambing will be required.     

Screening for Booroola (FecB) and Galway (FecXG) mutations in Indian sheep

This study reports the status of the Booroola (FecB) and Galway (FecX^G) mutations in Indian sheep breeds. The Kendrapada sheep (n = 46) was genotyped for the presence of FecB and FecX^G mutations, while the Garole (n = 34), Malpura (n = 30), and Decanni sheep (n = 15) for the FecX^G mutation. The FecB and FecX^G genotyping was carried out by forced restriction fragment length polymorphism PCR technique. In the present study, FecB mutation was discovered in the Kendrapada sheep of Orissa, which is now the second prolific sheep of India after the Garole. Out of 46 individuals of Kendrapada sheep, 26 were homozygous (BB), 15 heterozygous (B+) and 5 non-carriers (++) for the FecB mutation. The frequency of the FecB allele in this sample was about 0.73. Results indicated that the frequency of the FecB mutation is high, but the gene is not fixed in the population as reported in Garole sheep. None of sheep breeds carried the FecX^G mutation. The discovery of the FecB mutation in Kendrapada sheep will facilitate the use of FecB allele in improving the prolificacy of non-prolific sheep breeds of India.     

Natural and induced ovulation rate in prolific and non-prolific breeds of sheep in Ireland, Morocco and New Zealand

Ovulation rate, in mixed-age groups of prolific and non-prolific ewe breed types, after administration of a range of doses of PMSG (0, 375, 750 and 1500 i.u.) during the follicular phase of the oestrous cycle, were compared in Ireland, Morocco and New Zealand. The ewes in Ireland and Morocco were from the Finnish Landrace and Galway, and D'Man and Timhadite breeds, respectively. In New Zealand Booroola Merino x Romney ewes which had been previously identified as heterozygous carriers (F+) of the Booroola high fecundity gene and purebred Romneys were used to represent the prolific and non-prolific genotypes respectively; in addition a group of Booroola Merino x Romney non-carriers (++) of the major gene were also included for comparison. Ovulation rate at the oestrus which preceded stimulation with PMSG was also measured in all animals. In all 3 locations the ewes of the prolific genotype had a greater ovulation rate after PMSG stimulation than did the non-prolific controls. However, this association between prolificacy and response to PMSG was removed when ovulation rate after PMSG was transformed by dividing by the ovulation rate observed before PMSG administration. Despite the differences in the genetic basis of their high prolificacy the pattern of response to PMSG over the range of dosages used was similar in Finnish Landrace, D'Man and Booroola Merino x Romney (F+) ewes and all breeds had means of about 10 ovulations in response to 1500 i.u. PMSG. Amongst the non-prolific breeds, the Timhadite was the most responsive to PMSG although it had the lowest natural ovulation rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prolificacy genotypes at BMPR 1B,BMP15 and GDF9 genes in North African sheep breeds

The aim of this research was to investigate the genetic structure at BMPR 1B, BMP15 and GDF9 prolificacy genes in five sheep breeds reared in Tunisia: Barbarine, Queue Fine de L’Ouest, Noire de Thibar, Sicilo-Sarde and D’man. Genomic DNA of 204 sheep was investigated for the FecB^B (BMPR 1B), FecX^R, FecX^H, FecX^I, FecX^L, FecX^G, FecX^B (BMP15) and FecG^H (GDF9) mutations. The sequence variability of the different DNA fragments utilised for genotyping was further investigated by Single Stranded Conformation Polymorphism (SSCP) and sequencing. All the above-mentioned mutations were absent in the five sheep breeds examined. SSCP analysis and sequencing allowed the detection of two nucleotide variations. A non-functional mutation (T/C transition at nt 747 of BMP15 cDNA known as B3) was found at the BMP15 gene, in the Noire de Thibar breed; this mutation was first detected in the Belclare sheep. A new nucleotide change G/A at nt 1159 of BMP15 cDNA, causing the amino acid change A119T in the mature peptide, was detected in the Barbarine breed for the first time. The highly prolific D’man ewes were monomorphic for the absence of all the known prolificacy alleles.     

Polymorphism of FecB Gene in Nine Sheep Breeds or Strains and Its Effects on Litter Size, Lamb Growth and Development

Nine sheep breeds or strains, including 615 individuals were screened with forced PCR RFLP method for the FecB gene to study the polymorphism and its effects on litter size, body weight and body size. Results showed that the polymorphism frequencies of FecB gene were significantly imbalanced in these breeds or strains. The Hu sheep were all homozygous carriers of FecB gene(BB). In the Chinese Merino prolific meat strain, the genotype frequencies of BB, B+ and ++ were 51%, 30% and 19%, respectively, whereas all the other flocks had only the wild-type (++) genotype. Results within the Chinese Merino prolific meat strain showed that the mean litter size of ewes with genotype BB and B+ were 2.8 (±0.74) and 2.3 (±0.63) (P<0.05). whereas ++ genotype ewes had a litter size of only 1.2 (±0.68) (P<0.01). At day 90 after birth, the body weights of BB/B+ genotype lambs were higher than that of ++ genotype lambs (18.6±3.70 kg. 18.0±3.71 kg vs 15.6±2.22 kg, P<0.05). In addition, the heart girth and chest width of BB/B+ genotype lambs were significantly longer than those of the ++ lambs (P<0.05). No significant differences were observed in either body weight or body size at day 120. Litter size at first lambing from Hu at Natural Source Conservative Region was found to be significantly higher than that from the other two regions sampled (P<0.05). In addition to the additive effect on litter size, these findings showed for the first time that the FecB gene had a positive effect on early postnatal body growth.     

Screening for Booroola (FecB) and Galway (FecX) mutations in Indian sheep

This study reports the status of the Booroola (FecB) and Galway (FecX^G) mutations in Indian sheep breeds. The Kendrapada sheep (n = 46) was genotyped for the presence of FecB and FecX^G mutations, while the Garole (n = 34), Malpura (n = 30), and Decanni sheep (n = 15) for the FecX^G mutation. The FecB and FecX^G genotyping was carried out by forced restriction fragment length polymorphism PCR technique. In the present study, FecB mutation was discovered in the Kendrapada sheep of Orissa, which is now the second prolific sheep of India after the Garole. Out of 46 individuals of Kendrapada sheep, 26 were homozygous (BB), 15 heterozygous (B+) and 5 non-carriers (++) for the FecB mutation. The frequency of the FecB allele in this sample was about 0.73. Results indicated that the frequency of the FecB mutation is high, but the gene is not fixed in the population as reported in Garole sheep. None of sheep breeds carried the FecX^G mutation. The discovery of the FecB mutation in Kendrapada sheep will facilitate the use of FecB allele in improving the prolificacy of non-prolific sheep breeds of India.     

Inbreeding trends and genetic diversity in purebred sheep populations

Monitoring the rate of change in inbreeding and genetic diversity within a population is important to guide breeding programmes. Such interest stems from the impact of loss in genetic diversity on sustainable genetic gain but also the impact on performance (i.e. inbreeding depression). The objective of the present study was to evaluate trends in inbreeding and genetic diversity in 43 066 Belclare, 120 753 Charollais, 22 652 Galway, 78 925 Suffolk, 187 395 Texel, and 19 821 Vendeen purebred sheep. The effective population size for each of the six breeds was between 116.0 (Belclare population) and 314.8 (Charollais population). The Charollais population was the most genetically diverse with the greatest number of effective founders, effective ancestors, and effective founder genomes; conversely, the Belclare was the least genetically diverse population with the fewest number of effective founders, effective ancestors, and effective founder genomes for each of the six breeds investigated. Overall, the effective population sizes and the total genetic diversity within each of the six breeds were above the minimum thresholds generally considered to be required for the long-term viability of a population.     

Genetic markers for the Booroola fecundity (Fec) gene in sheep

Animals from the Booroola line of Australian Merino sheep are characterized by a high ovulation rate that can be attributed to the presence of a codominant allele (Fec ^B).The specific function of the gene has not been identified. Effective use of the trait within the sheep breeding industry requires one or more genetic markers that can distinguish between alternative alleles at the locus Fec. With a combination of DNA minisatellite markers and polymorphic protein markers, a cluster of seven minisatellite fragments has been identified as being linked to the Fec gene and to the ovine A blood group locus. The minisatellite fragments have been derived from multilocus probes and hence cannot be used to define the chromosomal location of the Fec gene or to serve as diagnostic markers for Fec. The derivation of cloned single locus markers from the minisatellite fragments will enable finer scale mapping of the Fec and the A blood group locus in sheep.     

Population structure and breed composition prediction in a multi-breed sheep population using genome-wide single nucleotide polymorphism genotypes

Knowledge of population structure and breed composition of a population can be advantageous for a number of reasons; these include designing optimal (cross)breeding strategies in order to maximise non-additive genetic effects, maintaining flockbook integrity by authenticating animals being registered and as a quality control measure in the genotyping process. The objectives of the present study were to 1) describe the population structure of 24 sheep breeds, 2) quantify the breed composition of both flockbook-recorded and crossbred animals using single nucleotide polymorphism BLUP (SNP-BLUP), and 3) quantify the accuracy of breed composition prediction from low-density genotype panels containing between 2000 and 6000 SNPs. In total, 9334 autosomal SNPs on 11 144 flockbook-recorded animals and 1172 crossbred animals were used. The population structure of all breeds was characterised by principal component analysis (PCA) as well as the pairwise breed fixation index (F_st). The total number of animals, all of which were purebred, included in the calibration population for SNP-BLUP was 2579 with the number of animals per breed ranging from 9 to 500. The remaining 9559 flockbook-recorded animals, composite breeds and crossbred animals represented the test population; three breeds were excluded from breed composition prediction. The breed composition predicted using SNP-BLUP with 9334 SNPs was considered the gold standard prediction. The pairwise breed F_st ranged from 0.040 (between the Irish Blackface and Scottish Blackface) to 0.282 (between the Border Leicester and Suffolk). Principal component analysis revealed that the Suffolk from Ireland and the Suffolk from New Zealand formed distinct, non-overlapping clusters. In contrast, the Texel from Ireland and that from New Zealand formed integrated, overlapping clusters. Composite animals such as the Belclare clustered close to its founder breeds (i.e., Finn, Galway, Lleyn and Texel). When all 9334 SNPs were used to predict breed composition, an animal that had a majority breed proportion predicted to be ≥0.90 was defined as purebred for the present study. As the panel density decreased, the predicted breed proportion threshold, used to identify animals as purebred, also decreased (≥0.85 with 6000 SNPs to ≥0.60 with 2000 SNPs). In all, results from the study suggest that breed composition for purebred and crossbred animals can be determined with SNP-BLUP using ≥5000 SNPs.     

DNA tests in prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation

Recent discoveries that high prolificacy in sheep carrying the Booroola gene (FecB) is the result of a mutation in the BMPIB receptor and high prolificacy in Inverdale sheep (FecX(I)) is the result of a mutation in the BMP15 oocyte-derived growth factor gene have allowed direct marker tests to be developed for FecB and FecX(I). These tests were carried out in seven strains of sheep (Javanese, Thoka, Woodlands, Olkuska, Lacaune, Belclare, and Cambridge) in which inheritance patterns have suggested the presence of major genes affecting prolificacy and in the prolific Garole sheep of India, which have been proposed as the ancestor of Australian Booroola Merinos. The FecB mutation was found in the Garole and Javanese sheep but not in Thoka, Woodlands, Olkuska, Lacaune, Belclare, and Cambridge sheep. None of the sheep tested had the FecX(I) mutation. These findings present strong evidence to support historical records that the Booroola gene was introduced into Australian flocks from Garole (Bengal) sheep in the late 18th century. It is unknown whether Javanese Thin-tailed sheep acquired the Booroola gene directly from Garole sheep from India or via Merinos from Australia. The DNA mutation test for FecB will enable breeding plans to be developed that allow the most effective use of this gene in Garole and Javanese Thin-tailed sheep and their crosses.     

A review of the effects of the Booroola gene (FecB) on sheep production

Booroola Merino (B^oM) ewes have a high ovulation rate and litter size which in 1980 was postulated to be due to the effects of a major gene (FecB). This was confirmed in breeding experiments and FecB was subsequently shown to be due to a mutation (BMPR-1B) on chromosome 6. The B^oM originated from an Australian commercial fine wool Merino flock (Booroola) and has been used in crossing experiments and for introgression of FecB into many breeds around the world to improve fecundity. The mutation has recently been found in native sheep breeds in India, China and Indonesia and it is likely that FecB in the Australian B^oM was derived from importations of Garole sheep from India in 1792 and 1793.The effects on production traits of the FecB mutation in a range of genetic comparisons, environments and production systems are reviewed. Comparisons involving B^oM crosses with various other breeds and contrasts of FecB homozygous (BB), heterozygous (B+) and non-carrier (++) genotypes in comparable background genotypes, including non-B^oM, have been summarised from 45 reports. The weighted mean effect for ewes carrying one copy of FecB (B+) was +1.3 (range +0.8 to +2.0) for ovulation rate and +0.7 (range +0.4 to +1.3) for litter size. The effect of a second copy (BB) was generally additive for ovulation rate, with little or no increase in litter size for BB ewes among B^oM crosses. However there was generally a further increase in litter size for BB ewes of about half the effect of one copy (B+) in the Indian and Chinese breeds. Poor lamb survival and lamb growth reduced the number of lambs weaned and total weight of lamb weaned by B+ ewes. Most studies still showed a small advantage for B+ ewes, although several reported negative effects. While embryo survival declines at higher ovulation rates, the effects of FecB per se are equivocal. There is some evidence of a higher non-pregnancy rate among homozygous BB ewes. Most studies reported lower birth weight and growth rate from B^oM cross lambs and lambs from crossbred ewes introgressed with FecB. However it is difficult to separate the effects of low background genetic merit for growth of the B^oM and the lower birth weight and growth rate of lambs from larger litters from the genetic effect of carrying FecB. There was little or no difference in growth rate between BB, B+ and ++ genotype lambs. For other traits including, seasonal oestrous activity, carcass and meat quality and wool production, there was no evidence of major effects of FecB. The opportunities for management and nutritional modification of FecB expression and implications for industry adoption are briefly discussed.     

Polymorphisms of KiSS-1 and GPR54 genes and their relationships with litter size in sheep

The KiSS-1 and GPR54 genes were studied as candidate genes for the prolificacy in sheep. Four pairs of primers were designed to detect single nucleotide polymorphisms of exon 1 of KiSS-1 gene and exon 1, exon 2 and partial exon 5 of GPR54 gene in high fecundity breeds (Small Tail Han and Hu sheep) and low fecundity breeds (Dorset, Texel and Corriedale sheep) by PCR-SSCP. Polymorphisms in exon 1 of KiSS-1 gene were detected in prolific Small Tail Han sheep (AA, AB and BB genotypes) and Hu sheep (AA and CC genotypes), no polymorphism was found in low fecundity sheep breeds (only AA genotype). Polymorphisms in exon 2 of GPR54 gene were detected in prolific Hu sheep (DD and EE genotypes) and no polymorphism was found in prolific Small Tail Han sheep and low fecundity sheep breeds (only DD genotype). No polymorphism was detected in exon 1 and partial exon 5 of GPR54 gene in five sheep breeds. The polymorphic genotypes were sequenced. While compared the BB genotype with the AA genotype, one nucleotide mutation (G1035A) was detected, which resulted in amino acid change, Val25Met. Five nucleotide mutations were detected from AA to CC genotype (C981T, C996T, T997C, C1034G, C1039T), and among them four caused amino acid changes, that is, Arg7Trp, Phe12Leu, Asn24Lys, Ala26Val. While compared the EE genotype with the DD genotype, two nucleotide mutations (T2360C, A2411C) were detected, which gave rise to amino acid changes, Met90Thr and Asp107Ala, respectively. Genotype frequencies of AA, BB and AB were 0.62, 0.05 and 0.33 in Small Tail Han sheep, respectively. The Small Tail Han sheep ewes with genotype BB or AB had 0.88 (P?<?0.05) or 0.51 (P?<?0.05) lambs more than those with genotype AA; the Small Tail Han sheep ewes with genotype BB had 0.37 (P?>?0.05) lambs more than those with genotype AB. These results preliminarily indicated that the KiSS-1 gene may have some association with prolificacy in sheep.     

GDF9 as a candidate gene for prolificacy of Small Tail Han sheep

Growth differentiation factor 9 (GDF9) which controls the fecundity of Belclare, Cambridge, Santa Ines, Moghani, Ghezel and Thoka ewes was studied as a candidate gene for the prolificacy of Small Tail Han sheep. According to the sequence of ovine GDF9 gene, six pairs of primers were designed to detect single nucleotide polymorphisms of two exons of GDF9 gene in both high fecundity breed (Small Tail Han sheep) and low fecundity breed (Dorset sheep) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Only the products amplified by primers 2-1 and 2-2 displayed polymorphisms. For primer 2-1, three genotypes (AA, AB and BB) were detected in both sheep breeds. Sequencing revealed one silent mutation (G477A) in exon 2 of GDF9 gene in the BB genotype in comparison with the AA, which was known as G3 mutation of GDF9 gene in Belclare and Cambridge ewes. The relationship of least squares means for litter size was AA?>?AB?>?BB in Small Tail Han sheep (P?>?0.05). For primer 2-2, two genotypes (CC and CD) were detected in both sheep breeds. Sequencing revealed one novel single nucleotide mutation (G729T) in exon 2 of GDF9 gene in the CD genotype in comparison with the CC, which resulted in an amino acid change (Gln243His). The ewes with mutation heterozygous genotype CD had 0.77 (P?相似文献   

None of polymorphism of ovine fecundity major genes FecB and FecX was tested in goat

The polymorphism of mutation Q249R in BMPR-IB gene (FecB) and loci FecX^I, FecX^H, FecX^G, FecX^B in BMP15 gene was analyzed by forced PCR-RFLP method in 550 individuals from 6 flocks or breeds of goats with litter size varied from 1.4 to 2.7 including Boer (209), Haimen (128), second generation of Boer goat crossed with Huanghuai goat (82), Huanghuai (71), Nubi (37) and Matou (23) goat. None of mutations was detected in these goat breeds and their crossbreed. These results suggest that fecundity of goat is not linked to the same loci in BMPR-IB and BMP15 as sheep. Therefore, it is necessary to seek for other genes or loci in order to develop marker assistance selection techniques and study the prolific mechanism of the goat.