Microbiome composition as a potential predictor of longevity in rabbits.

BACKGROUND: Longevity and resilience are two fundamental traits for more sustainable livestock production. These traits are closely related, as resilient animals tend to have longer lifespans. An interesting criterion for increasing longevity in rabbit could be based on the information provided by its gut microbiome. The gut microbiome is essential for regulating health and plays crucial roles in the development of the immune system. The aim of this research was to investigate if animals with different longevities have different microbial profiles. We sequenced the 16S rRNA gene from soft faeces from 95 does. First, we compared two maternal rabbit lines with different longevities; a standard longevity maternal line (A) and a maternal line (LP) that was founded based on longevity criteria: females with a minimum of 25 parities with an average prolificacy per parity of 9 or more. Second, we compared the gut microbiota of two groups of animals from line LP with different longevities: females that died/were culled with two parities or less (LLP) and females with more than 15 parities (HLP). RESULTS: Differences in alpha and beta diversity were observed between lines A and LP, and a partial least square discriminant analysis (PLS-DA) showed a high prediction accuracy (> 91%) of classification of animals to line A versus LP (146 amplicon sequence variants (ASV)). The PLS-DA also showed a high prediction accuracy (> 94%) to classify animals to the LLP and HLP groups (53 ASV). Interestingly, some of the most important taxa identified in the PLS-DA were common to both comparisons (Akkermansia, Christensenellaceae R-7, Uncultured Eubacteriaceae, among others) and have been reported to be related to resilience and longevity. CONCLUSIONS: Our results indicate that the first parity gut microbiome profile differs between the two rabbit maternal lines (A and LP) and, to a lesser extent, between animals of line LP with different longevities (LLP and HLP). Several genera were able to discriminate animals from the two lines and animals with different longevities, which shows that the gut microbiome could be used as a predictive factor for longevity, or as a selection criterion for these traits.

Genetic variant of the sheep E2F8 gene and its associations with litter size.

The economic efficiency of sheep breeding, aiming to enhance productivity, is a focal point for improvement of sheep breeding. Recent studies highlight the involvement of the Early Region 2 Binding Factor transcription factor 8 (E2F8) gene in female reproduction. Our group's recent genome-wide association study (GWAS) emphasizes the potential impact of the E2F8 gene on prolificacy traits in Australian White sheep (AUW). Herein, the purpose of this study was to assess the correlation of the E2F8 gene with litter size in AUW sheep breed. This work encompassed 659 AUW sheep, subject to genotyping through PCR-based genotyping technology. Furthermore, the results of PCR-based genotyping showed significant associations between the P1-del-32bp bp InDel and the fourth and fifth parities litter size in AUW sheep; the litter size of those with genotype ID were superior compared to those with DD and II genotypes. Thus, these results indicate that the P1-del-32bp InDel within the E2F8 gene can be useful in marker-assisted selection (MAS) in sheep.

Association of polymorphism in the promotor area of the caprine BMPR1B gene with litter size and body measurement traits in Damani goats.

This study aimed to explore polymorphisms in the promoter region of the caprine BMPR1B (Bone morphogenetic protein receptor 1 beta) gene and its association with body measurement and litter size traits in Damani does. A total of 53 blood samples were collected to analyze the association between the BMPR1B gene polymorphism and 11 phenotypic traits in Damani female goats. The results revealed that three novel SNPs were identified in the promoter region of the caprine BMPR1B gene, including g.67 A > C (SNP1), g.170 G > A(SNP2), and g.501A > T (SNP3), among which the SNP1 and SNP2 were significantly (p < 0.05) associated with litter size and body measurement traits in Damani goats. In SNP1 the AC genotype could be used as a marker for litter size, and the CC genotype for body weight in Damani goats. In SNP2, the genotype GG was significantly (p < 0.05) associated with ear and head length. Therefore, we can conclude from the present study, that genetic variants AC and CC of the caprine BMPR1B gene could be used as genetic markers for economic traits through marker-assisted selection for the breed improvement program of the Damani goat.

Genome-Wide DNA Methylation Analysis and Functional Validation of Litter Size Traits in Jining Grey Goats.

DNA methylation (DNAm) is associated with the reproductive system. However, the genetic mechanism through which DNAm regulates gene expression and thus affects litter size in goats is unclear. Therefore, in the present work, genome-wide DNAm profiles of HP and LP Jining Grey goat ovary tissues were comprehensively analyzed via WGBS, and RNA-Seq data were combined to identify candidate genes associated with litter size traits in the Jining Grey goat. Finally, BSP and RT-qPCR were used to verify the sequencing results of the key genes. Notably, the DNMT genes were downregulated at the expression level in the HP group. Both groups exhibited comparable levels of methylation. A total of 976 differentially methylated regions (DMRs) (973 DMRs for CG and 3 DMRs for CHG) and 310 differentially methylated genes (DMGs) were identified in this study. Through integration of WGBS and RNA-Seq data, we identified 59 differentially methylated and differentially expressed genes (DEGs) and ultimately screened 8 key DMGs (9 DMRS) associated with litter size traits in Jining Grey goats (SERPINB2: chr24_62258801_62259000, NDRG4: chr18_27599201_27599400, CFAP43: chr26_27046601_27046800, LRP1B. chr2_79720201_79720400, EPHA6: chr1_40088601_40088800, TTC29: chr17_59385801_59386000, PDE11A: chr2_117418601_117418800 and PGF: chr10_ 16913801_16914000 and chr10_16916401_16916600). In summary, our research comprehensively analyzed the genome-wide DNAm profiles of HP and LP Jining Grey goat ovary tissues. The data findings suggest that DNAm in goat ovaries may play an important role in determining litter size.

FecB Was Associated with Litter Size and Follows Mendel's Laws of Inheritance When It Transited to Next Generation in Suhu Meat Sheep Breeding Population.

In order to investigate the effect of FecB on litter size and growth and development traits of Suhu meat sheep and the inheritance patterns of FecB between parents and offspring in the population. In this experiment, 2241 sheep from the Suhu meat sheep population were tested for FecB using capillary electrophoresis. We combined the lambing records of 473 ewes, the growth trait records of 881 sheep at both the birth and weaning (2-month-old) stages, and the complete genealogical records of 643 lambs to analysis the distribution of FecB in the Suhu meat sheep breeding population, its effect on litter size of ewes, growth and development of lambs, and the inheritance patterns of FecB. The results showed that there were three genotypes of FecB in the Suhu meat sheep population, namely the AA genotype, AG genotype, and GG genotype. FecB in this population has a moderate polymorphism (0.25 < PIC < 0.5), and deviates from Hardy-Weinberg disequilibrium (p < 0.05). The litter size of GG genotype ewes was significantly higher than that with the AG and AA genotypes (p < 0.01). A Chi-square test showed that the inheritance patterns of FecB follows Mendel's Laws of Inheritance (p > 0.05). An association analysis of different genotypes of FecB with body weight and body size of Suhu meat sheep at birth and weaning revealed that FecB adversely affects the early growth and development of Suhu meat sheep. In summary, FecB can improve the litter size of ewes but it has negative effects on the early growth and survival rate of lambs in sheep. Therefore, FecB test results and feeding management measures should be comprehensively applied to improve the reproductive performance of ewes, the survival rate and production performance of lambs in sheep production, and thus improve the economic benefits of sheep farms.

An Identification of Functional Genetic Variants in B4GALNT2 Gene and Their Association with Growth Traits in Goats.

ß-1,4-N-acetylgalactosamine transferase 2 (B4GALNT2) is a vital candidate gene that affects the growth traits in sheep. However, whether it has the same function in goats remains to be investigated further. This study selected 348 Nanjiang Yellow goats, screened all exons, and conserved non-coding regions of the B4GALNT2 gene for single-nucleotide polymorphisms (SNPs). Our results revealed the presence of a synonymous mutation, rs672215506, within the exon of the B4GALNT2 gene in the Nanjiang Yellow goat population. The mutation resulted in a decrease in the mRNA stability of the B4GALNT2 gene. The results of SNP detection of the conserved non-coding region of the B4GALNT2 gene showed five potential regulatory SNPs in the Nanjiang Yellow goat population. Except for rs66095343, the ~500 bp fragments of the other four SNPs (rs649127714, rs649573228, rs652899012, and rs639183528) significantly increased the luciferase activity both in goat skeletal muscle satellite cells (MuSCs) and 293T cells. The genetic diversity indexes indicated low or intermediate levels for all six SNPs analyzed, and the genotype frequencies were in Hardy-Weinberg equilibrium. Association analysis showed that rs660965343, rs649127714, and rs649573228 significantly correlate with growth traits in the later stage of growth and development of Nanjiang Yellow goats. The haplotype combinations of H2H3 and H2H2 had higher body weight and greater body size. Moreover, H2H2 haplotype combinations significantly correlated with the litter size of the Nanjiang Yellow goats. The results of our study demonstrate the potential role of the B4GALNT2 gene as a functional genetic marker in the breeding programs of Nanjiang Yellow goats.

A repertoire of single nucleotide polymorphisms (SNPs) of major fecundity BMPR1B gene among 75 sheep breeds worldwide.

The BMPR1B gene is a major determinant of sheep reproductive capacity. Previous studies revealed that Q249R (FecB) is a profound variant of BMPR1B that influences the ovulation rate and litter size in sheep. However, unlike Q249R locus, the full spectrum of single nucleotide polymorphisms (SNPs) within BMPR1B has not been extensively studied. A systematic screen of SNPs in BMPR1B would facilitate the discovery of novel variants that are associated with litter size. This study aimed to investigate SNPs in the BMPR1B gene via whole genome sequence (WGS) data from 2409 individuals of 75 sheep breeds worldwide. Herein, a total of 9688 variants were screened, among which 15 were coding variants and 8 were novel changes. Specifically, we presented the most comprehensive frequency distribution map of the well-known FecB mutation to date. Besides, among the above-mentioned SNPs, one synonymous mutation (g.30050773C > T) was found to be likely under selection and is potentially associated with fecundity in Duolang sheep. Thus, our study greatly expands the variation repertoire of the ovine BMPR1B gene and provides a valuable resource for exploring causative mutations and genetic markers associated with litter size.

Genetic basis of sow hyperprolificacy and litter size optimization based on a genome-wide association study.

Over the last few decades, there has been a constant increase in sow litter size, the consequences of which include parturition duration extension, an increase in the percentage of stillborn and hypoxic piglets, and increased variation in piglet birth weight, which reduces their vitality. As such, it seems clear that further increasing sow fertility will generate difficulties and costs in rearing numerous litters with low birth weights. Therefore, the current study aimed to analyze the genetic background of sow hyperprolifcacy using a genome-wide association study (GWAS). The research included 144 sows in the maternal component, divided into two equal groups. The first group (control) consisted of females giving birth to the optimal number of piglets in their third and fourth litters (14-16), while the second group (cases) included those with excessive litter size (>16). The analyzed sows were genotyped using Illumina's PorcineSNP60v2 BeadChip microarray, comprising 64,232 single nucleotide polymorphisms (SNPs). Statistical analysis using R included quality control of genotyping data and GWAS analysis based on five logistic regression models (dominant, codominant, overdominant, recessive, and log-additive) with a single SNP marker as the explanatory variable. On this basis, one SNP (SIRI0000069) was identified on chromosome seven within the EFCAB11 (EF-hand calcium binding domain 11) gene that had a statistically significant effect on sow hyperprolificacy. Additionally, ten SNPs (INRA0007631, ALGA0011600, ALGA0043433, ALGA0043428, M1GA0010535 ALGA00443338, ALGA0087116, MARC0056787, ALGA0112928, and ALGA0089047) had a relationship with the analyzed feature at a level close to significance, set at 1-5. These SNPs appear important since they are located on chromosomes on which a large number of quantitative trait loci (QTLs) and SNPs associated with reproductive characteristics, including litter size, have been identified.

Genetic variation in the BLM gene and its expression in the ovaries is closely related to kidding number in goats.

Bloom (BLM) helicase plays an important role in DNA replication and the maintenance of genome integrity. BLM protein deficiency, which plays a vital role in the sperm-egg union and germ-cell development during reproduction, can lead to severe DNA damage in goats. However, the effect of BLM protein deficiency on goat litter size has not been reported. Herein, we studied the association between the genetic variation in the BLM gene and the number of kids per litter in Guizhou white goats. We explored differences in the expression of the BLM protein in the follicles of single and multi-kid nanny goats. We also analyzed the effects of dysregulated BLM gene expression on the proliferation and apoptosis of ovarian granulosa cells and the expression of genes related to follicle development in goats. Five single nucleotide polymorphism (SNP) loci, including the non-synonymous mutations g.38179 A > G, g.40626 G > C and g.89621 T > G; the intron synonymous mutation g.56961 G > A and the exon synonymous mutation g.65796 C > T were found in the BLM gene. All SNPs loci were in Hardy-Weinberg equilibrium, and correlation analysis showed that the g.65796 C > T and g.89621 T > G loci polymorphism was strongly associated with litter size in the first three litters (P < 0.05). The diplogenotype Hap 2/2 (AAGGAACCTT) showed no significant difference in litter size between different births, indicating that the diploid genotype is stable in different litter sizes. Bioinformatics analysis showed that three non-synonymous mutation loci (p.T488A, p.A662S, and p.S1373A) could affect BLM protein stability, and mutations in p.T488A and p.S1373A led to changes in amino acid polarity and associated interactions. qPCR results showed that the expression level of the BLM gene in the uterus and ovaries of TT genotype nanny goats was significantly higher than that of GG genotype nanny goats. Indirect immunofluorescence assay (IF) showed that the BLM protein was significantly overexpressed in both the primordial and growing follicles of nanny goats with multiple kids (P < 0.01). Disrupting BLM gene expression in the ovarian granulosa cells down-regulated the expression of the Cyp19A1 gene. It also significantly inhibited the proliferation of follicles and induces early apoptosis of the granulosa cells. These findings confirm that polymorphism in the BLM gene is closely related to the littering traits of Guizhou white goats, and it affects the reproductive performance of nanny goats by regulating the development of the oocytes and granulosa cells. This work provides new evidence on the regulatory effect of the BLM gene on the litter size of nanny goats.

The novel C268A variant of BMP2 is linked to the reproductive performance of Awassi and Hamdani sheep.

BACKGROUND: Prolificacy-associated genetic markers can be utilized to enhance litter size in the sheep breeding industry. Sheep reproduction is influenced by a multitude of genes, including bone morphogenetic protein 2 (BMP2). This study aimed to explore the potential relationship between variability in the BMP2 gene and reproductive performance in Awassi and Hamdani ewes. METHODS AND RESULTS: The genomic DNA was extracted from 99 single-progeny ewes and 101 twin ewes. Polymerase chain reaction (PCR) was employed to produce an amplicon consisting of four sequence fragments: 277 bp, 251 bp, 331 bp, and 340 bp, from exons 1, 2, 3, and 4 of the BMP2 gene, respectively. Three genotypes were identified for amplicons in exon 4 with 340-bp lengths: CC, CA, and AA. Upon analyzing the sequence of the CA genotype 382 C > A, a novel mutation was discovered in this genotype. A robust association was identified between the single nucleotide polymorphisms (SNP) 382 C > A and reproductive performance through statistical analysis. An important distinction was discovered between ewes carrying SNP 382 C > A and those carrying CC in terms of litter sizes, twinning rates, lambing rates, and days to lambing. An analysis of logistic regression revealed a significant association between litter size and the 382 C > A SNP. There was a decrease in lamb production among ewes with the CC genotype compared to those with the CA and AA genotypes. CONCLUSIONS: These results indicate that the SNP variant 382 C > A has a positive influence on the reproductive performance of Awassi and Hamdani sheep. Sheep carrying the 382 C > A SNP exhibit increased litter size and overall productivity compared to those without the SNP.

Detection of polymorphisms in six genes and their association analysis with litter size in sheep.

Litter size in sheep is a complex trait controlled by micro-effective polygenes. APAF1, CLSTN2, CTH, PLCB1, PLCB4, and CHST11 are all involved in mammalian reproduction. However, the effects of these genes on litter size in sheep are still unclear. Therefore, in this study, we used Sequenom MassARRAY® SNP assay technology to type the single nucleotide polymorphisms (SNPs) loci of six genes in five sheep breeds. The results showed that most sheep breeds contain three genotypes at each locus. Then, we conducted population genetic analysis on the SNPs of six genes and found that the polymorphic information content in all sheep breeds ranged from 0 to 0.37, and most sheep breeds were in Hardy-Weinberg equilibrium (p > 0.05). In addition, association analysis in Small Tail Han sheep indicated that the rs399534524 locus in CLSTN2 was highly associated with first parity litter size, and litter size in ewes with CT genotype was higher than that in ewes with CC genotype or TT genotype. Furthermore, the rs407142552 locus in CTH was highly associated with second parity litter size in Small Tail Han sheep, and litter size in ewes with CT genotype was higher than that in ewes with TT genotype. Finally, we predicted the CTH and CLSTN2 protein interaction network and found that HTR1E, NOM1, CCDC174 and ALPK3 interact with CLSTN2 and have been reported as candidate genes related to litter size in sheep. These results suggest that they may be useful genetic markers for increasing litter size in sheep.

Whole-genome resequencing reveals new mutations in candidate genes for Beichuan-white goat prolificacya.

In this study, we evaluated the copy number variation in the genomes of two groups of Beichuan-white goat populations with large differences in litter size by FST method, and identified 1739 genes and 485 missense mutations in the genes subject to positive selection. Through functional enrichment, ITGAV, LRP4, CDH23, TPRN, RYR2 and CELSR1 genes, involved in embryonic morphogenesis, were essential for litter size trait, which received intensive attention. In addition, some mutation sites of these genes have been proposed (ITGAV: c.38C > T; TPRN: c.133A > T, c.1192A > G, c.1250A > C; CELSR1: c.7640T > C), whose allele frequencies were significantly changed in the high fecundity goat group. Besides, we found that new mutations at these sites altered the hydrophilicity and 3D structure of the protein. Candidate genes related to litter size in this study and their missense mutation sites were identified. These candidate genes are helpful to understand the genetic mechanism of fecundity in Beichuan white goat, and have important significance for future goat breeding.

Genome-wide association studies for the number of piglets born alive and dead in Dongliao black pigs.

Litter size (total number born) trait has a great impact on the economic success of pork production. The total number born consists of the number of piglets born alive and dead. To clarify the genetic background of litter size, genome-wide association studies were undertaken in the present study. Samples of DNA were collected and genotyped using the Porcine 50K BeadChip from 723 Dongliao Black sows. Using three different models (BLINK, FarmCPU, and MLM), a total of 155 significant SNPs were discovered, six of which had been reported in previous pig reproduction association studies. We suggest that rs81318434, located in the GLI3 gene, might be the promising candidate affecting litter size trait. Our findings may provide insights for uncovering the genetic mechanisms for the litter size of pigs.

Differential sensitivity of climate conditions on birth weight genetic values in mice divergently selected for birth weight residual variance.

After 32 generations of a divergent selection experiment for residual variance of birth weight in mice, two divergent lines were thus obtained: the heterogeneous line (H-line) and the homogeneous line (L-line). Throughout the generations, differences were observed between the two lines in traits such as litter size, survival at weaning, and birth weight variability caused by unidentified environmental conditions. The L-line exhibited advantages in terms of higher survival rates, larger litter sizes, and less sensitivity to changes in food intake. The study is an examination of the effects of climate as an environmental factor on the performance of these animals. Climate factors including maximum, minimum, and mean temperature (T), humidity (H), and TH index; at three stages (the fecundation, a week before the parturition and the parturition), were linked to a birth weight dataset consisting of 22,614 records distributed as follows: 8,853 corresponding to the H-line, 12,649 to the L-line, and 1,112 to the initial population. Out of the 27 analyzed climatic variables, the maximum temperature 1 wk before parturition (MXTW) was identified as the most influential when comparing heteroscedastic models with the deviance information criterion. The order of Legendre polynomial to apply in the following random regression model was tested by a cross-validation using homoscedastic models. Finally, MXTW was compared on how it affected the two divergent lines by analyzing predicted breeding values (PBV) obtained from a random regression heteroscedastic model. The mean PBV of the H-line in the first generation showed a range of 0.070 g with a negative slope, which was 35 times higher than the range obtained for the L-line, which varied within 0.002 g. In the last generation of selection, the H-line exhibited greater instability of PBV across temperatures, with a difference of 0.101 g between the maximum and minimum mean PBV, compared to 0.017 g for the L-line. The standard deviations of the slopes in the H-line were more dispersed than in the L-line. Unlike the H-line, the L-line had slopes that were not significantly different from 0 throughout the generations of selection, indicating greater stability in response to MXTW variations. The H-line exhibited a higher sensitivity to changes in MXTW, particularly in birth weight, with the L-line being more stable. The selection for uniformity of birth weight could lead to less sensitive animals under environmental changes.

Two mice lines obtained by divergent selection for birth weight residual variance were used to determine whether environmental factors could differently affect the homogeneous and heterogeneous lines. The maximum temperature 1 wk before parturition (MXTW) had the higher impact on the birth weight of the animals. A random regression model showed the individual trajectory of birth weight throughout the changes in MXTW. It was evident that the homogeneous line is less susceptible to changes in climate. This result, therefore, supports the hypothesis that the selection for homogeneity in production animals is more advantageous. More robust animals are obtained that can better cope with changes in climate without compromising their productive traits.

An Integrative ATAC-Seq and RNA-Seq Analysis of the Endometrial Tissues of Meishan and Duroc Pigs.

Meishan pigs are a well-known indigenous pig breed in China characterized by a high fertility. Notably, the number of endometrial grands is significantly higher in Meishan pigs than Duroc pigs. The characteristics of the endometrial tissue are related to litter size. Therefore, we used the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA-sequencing (RNA-seq) to analyze the mechanisms underlying the differences in fecundity between the breeds. We detected the key transcription factors, including Double homeobox (Dux), Ladybird-like homeobox gene 2 (LBX2), and LIM homeobox 8 (Lhx8), with potentially pivotal roles in the regulation of the genes related to endometrial development. We identified the differentially expressed genes between the breeds, including SOX17, ANXA4, DLX3, DMRT1, FLNB, IRF6, CBFA2T2, TFCP2L1, EFNA5, SLIT2, and CYFIP2, with roles in epithelial cell differentiation, fertility, and ovulation. Interestingly, ANXA4, CBFA2T2, and TFCP2L1, which were upregulated in the Meishan pigs in the RNA-seq analysis, were identified again by the integration of the ATAC-seq and RNA-seq data. Moreover, we identified genes in the cancer or immune pathways, FoxO signaling, Wnt signaling, and phospholipase D signaling pathways. These ATAC-seq and RNA-seq analyses revealed the accessible chromatin and potential mechanisms underlying the differences in the endometrial tissues between the two types of pigs.

Genomic Scanning of Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs.

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a genomic scan of the whole pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto). The datasets consisted of 2069 (338 sows) and 2028 (327 sows) records of litter size (Total Number Born and Number Born Alive) for the Entrepelado and Retinto varieties. All sows were genotyped using the Geneseek GGP PorcineHD 70 K chip. We employed the Unfavorable Haplotype Finder software to extract runs of homozygosity (ROHs) and conducted a mixed-model analysis to identify highly significant differences between homozygous and heterozygous sows for each specific ROH. A total of eight genomic regions located on SSC2, SSC5, SSC7, SSC8, and SSC13 were significantly associated with inbreeding depression, housing some relevant genes such as FSHR, LHCGR, CORIN, AQP6, and CEP120.

Relationships of genomic estimated breeding values for age at puberty, birth weight, and growth during development in normal cyclic and acyclic gilts.

Managing replacement gilts to reach optimal body weight and growth rate for boar stimulation and first breeding is a key component for sow reproductive longevity and producer profitability. Failure to display pubertal estrus remains a major reason that gilts are culled from the herd. Puberty is metabolically gated so evaluating phenotypic and genetic relationships between birth weight and growth traits with age at puberty and acyclicity can provide valuable insight for efficient gilt development. Data on a litter of origin of the gilt, average daily gain at different stages of development, and age at puberty were available for age-matched cyclic (n = 4,861) and acyclic gilts (prepubertal anestrus, n = 578; behavioral anestrus, n = 428). Genomic estimated breeding values were predicted for each trait using genomic best linear unbiased prediction. Primiparous sows produced more acyclic gilts than multiparous sows (P < 0.05). Accounting for effects of parity and litter size, prepubertal anestrus gilts were heavier at birth and behaviorally anestrus gilts grew faster during the finisher period compared to cyclic gilts (P < 0.05), reflecting possible prenatal programming that negatively affects optimal pubertal development and antagonistic effects between adolescent growth and expression of estrus of gilts from first parity sows. Regression of phenotypic age at puberty with lifetime growth rate (birth to selection) showed a negative linear relationship whereas genomic estimated breeding values showed a negative quadratic relationship indicating that gilts with the least and greatest growth are less optimal as replacements. The slopes of these relationships are small with low negative phenotypic (r = -0.06) and genetic correlations (r = -0.13). The addition of data from acyclic gilts did not substantially change the estimates for genetic relationships between growth and pubertal onset. Although this study identified differences in birth weight and growth rate between cyclic and acyclic gilts the genetic relationships are weak, suggesting that genetic selection for these traits can be achieved separately. Avoiding the smallest and largest gilts in a cohort born to first parity sows could result in gilts with optimal development and reduce the proportion of replacement gilts that are acyclic.

Failure to display pubertal estrus is major reason replacement gilts are culled from the herd. Two types of prebreeding estrus failure are delay in attaining puberty due to sexual immaturity known as prepubertal anestrus (PPA) and silent ovulation without signs of estrus known as behavioral anestrus (BA). For efficient gilt development, it is important to understand what contributes to these acyclic phenotypes. Comparison of birth weight and growth rate in age-matched cyclic, PPA, and BA gilts showed that PPA gilts were heavier at birth and BA gilts grew faster during the finisher period, reflecting negative effects of larger birth weight and faster growth on sexual maturity and behavioral estrus. The genetic relationship between growth and puberty onset indicated that gilts with the least and greatest growth rates are less optimal as replacements. A selection criterion to avoid the smallest and largest gilts in a cohort could result in gilts with optimal development for boar stimulation and reduce the proportion of acyclic gilts. This management strategy would be most effective if targeted to first parity sows.

Polymorphism of GTF2A1 gene is associated with litter size in sheep.

General transcription factor IIA subunit 1 (GTF2A1) is required for transcriptional activation from most promoters in eukaryotic transcription. Previous whole-genome association analyses articles have predicted the effect of this gene on lambing in sheep. In the study, a total of nine insertion/deletion (indel) variants named L1 to L9 in the gene were selected to detect in 550 Australian White sheep (AuW) adult ewes. The polymorphisms were detected in four loci (L1, L2, L3 and L8locus) and the polymorphism information content (PIC) values were 0.270, 0.375, 0.372 and 0.314. Further, our study revealed that L1, L2 and L3 loci of GTF2A1 gene were significantly related to the first parity litter size and the polymorphism of L8 was significantly correlated with litter size in the second parity. In details, for the first parity, individuals with the II genotype of the L1 locus had higher little size than that with the ID genotype, individuals with the ID and DD genotype of the L2 locus had higher little size than that with the II genotype, and individuals with the DD genotype of the L3 locus had higher little size than that with the II genotype. All four loci do not follow to Hardy-Weinberg equilibrium, and have no linkage between them. In conclusion, the polymorphisms of GTF2A1 were confirmed and analysis results demonstrated that there are some relevance between difference genotypes and litter size, and these findings may provide new insights for accelerating sheep molecular breeding through molecular marker-assisted selection (MAS).

Group size planning for breedings of gene-modified mice and other organisms following Mendelian inheritance.

Colony management of gene-modified animals is time-consuming, costly and affected by random events related to Mendelian genetics, fertility and litter size. Careful planning is mandatory to ensure successful outcomes using the least number of animals, hence adhering to the 3R principles of animal welfare. Here we have developed an R package, accessible also through an interactive public website, that optimizes breeding design by providing information about the optimal number of breedings needed to obtain defined breeding outcomes, taking into account specific species, strain, or line properties and success probability. Our software also enables breeding planning for balanced male-to-female ratio or single-sex experiments. We show that, for single-sex designs, the necessary number of breedings is at least doubled compared to the use of all born animals. While the presented tool provides preset parameters for the laboratory mouse, it can be readily used for any other species.

Effect of ewe birth litter size and estimation of genetic parameters on ewe reproductive life traits.

Ewe lifetime productivity has economic implications for producers because shorter lifetime productivity results in less profit. Productive years of ewes from extensive, range-based systems of the United States West are generally less than ewes from more temperate regions of the United States. Accordingly, ewes from range-based systems, especially those employing shed-lambing strategies, have been selected for increased litter size to offset decreased lifetime productivity. However, the relationship of the ewe's birth litter size (ELSB) has not been considered a potential contributor to lifetime productivity. Longevity (number of productive years, n = 1 per population) and stayability (probability to survive to the next age; ages 2-7 years, n = 6 per population) were investigated to understand ELSB effects on productive life. Columbia, Polypay, Rambouillet, and Targhee breeds were used in this study. Across-breed (n = 11 550) and within-breed (Columbia, n = 4 398; Polypay, n = 4 534; Rambouillet, n = 5 922; Targhee, n = 6 482) analyses were used. Depending on the population, records spanned from 1950 to 2008, where ewe's birth year was included as a fixed effect in the animal model using restricted maximum likelihood estimation procedures. Fixed effects investigated included ELSB (single-, twin-, or triplet-born) and ewe breed (across-breed analyses only). Regardless of trait or population used, heritability ranged from 0.06 ± 0.02 to 0.34 ± 0.03, where stayability at younger ages had the highest estimates. The breed effect was significant in all across-breed analyses (0.0001 ≤ P ≤ 0.038; n = 7), where Polypay, a breed selected for accelerated lambing and increased fertility, averaged shorter productive life or had a lower probability of survival to the next age compared with other breeds (longevity: 0.009 ≤ P ≤ 0.223; stayability: 0.000 ≤ P ≤ 0.842). The ELSB was significant in 60% (n = 5) and 37% (n = 30) of longevity and stayability analyses, respectively. Except for Targhee, all analyses showed ewes born in smaller litter sizes were associated with longer productive lives or higher probability of surviving to the next age, particularly in across-breed analyses (e.g., longevity: single- vs twin-born ewes, P = 0.004; vs triplet-born ewes, P = 0.003). This study provides evidence that increasing prolificacy in ewes from extensive, range-based production systems may impact productive life. Due to the low heritability of these traits, additional investigation into modeling these traits with dominance effects and litter size needs to be conducted.