Genes and Pathways Affecting Sheep Productivity Traits: Genetic Parameters, Genome-Wide Association Mapping, and Pathway Enrichment Analysis.
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SUBMITTER: Esmaeili-Fard SM
PROVIDER: S-EPMC8355708 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite their economic value, sheep remain relatively poorly studied animals in terms of the number of known loci and genes associated with commercially important traits. This gap in our knowledge can be filled in by performing new genome-wide association studies (GWAS) or by re-analyzing previously documented data using novel powerful statistical methods. This study is focused on the search for new loci associated with meat productivity and carcass traits in sheep. With a multivariate approach applied to publicly available GWAS results, we identified eight novel loci associated with the meat productivity and carcass traits in sheep. Using an in silico follow-up approach, we prioritized 13 genes in these loci. One of eight novel loci near the FAM3C and WNT16 genes has been replicated in an independent sample of Russian sheep populations (N = 108). The novel loci were added to our regularly updated database increasing the number of known loci to more than 140.
| S-EPMC8002146 | biostudies-literature
Project description:Complex traits such as crop performance and human diseases are controlled by multiple genetic loci, many of which have small effects and often go undetected by traditional quantitative trait locus (QTL) mapping. Recently, bulked segregant analysis with large F2 pools and genome-level markers (named extreme-QTL or X-QTL mapping) has been used to identify many QTL. To estimate parameters impacting QTL detection for X-QTL mapping, we simulated the effects of population size, marker density, and sequencing depth of markers on QTL detectability for traits with differing heritabilities. These simulations indicate that a high (>90%) chance of detecting QTL with at least 5% effect requires 5000× sequencing depth for a trait with heritability of 0.4-0.7. For most eukaryotic organisms, whole-genome sequencing at this depth is not economically feasible. Therefore, we tested and confirmed the feasibility of applying deep sequencing of target-enriched markers for X-QTL mapping. We used two traits in Arabidopsis thaliana with different heritabilities: seed size (H(2) = 0.61) and seedling greening in response to salt (H(2) = 0.94). We used a modified G test to identify QTL regions and developed a model-based statistical framework to resolve individual peaks by incorporating recombination rates. Multiple QTL were identified for both traits, including previously undiscovered QTL. We call our method target-enriched X-QTL (TEX-QTL) mapping; this mapping approach is not limited by the genome size or the availability of recombinant inbred populations and should be applicable to many organisms and traits.
| S-EPMC4704726 | biostudies-literature
Project description:This work aimed to estimate genetic parameters for traits related to semen production and quality in Spanish dairy sheep breeds. For that, ejaculates of rams from Assaf, Churra, Latxa Cara Negra, Latxa Cara Rubia, and Manchega breeds were analyzed to measure volume, semen concentration, and motility. Estimates of variance components were obtained with multiple-trait animal models using the average information REML method in the BLUPF90 family of programs. Repeatability estimates for all the traits were also calculated, with values ranging from 0.077 to 0.304 for the motility and the semen concentration traits, respectively. Heritability estimates were of low to moderate magnitude, ranging from 0.014 (motility in Latxa Cara Rubia) to 0.198 (volume in Churra), although the estimates differed among the breeds. The estimated genetic correlations among the three semen traits showed adequate precision only in the MAN breed. The heritability estimates for the semen traits reported in the present paper suggest an adequate response to selection. The practical extension of these results to the other breeds studied here will be secondary to the estimation of more reliable genetic correlations in these breeds.
| S-EPMC6940766 | biostudies-literature
Project description:Background and aimSheep productivity in developing countries is crucial, as this animal is an essential source of meat and wool. Myostatin (MSTN) plays an important role in the regulation of muscle mass through the regulation of muscle growth, differentiation, and regeneration. The present study sought to investigate genetic variation in the first intron of the MSTN gene and the association of variants with growth traits in major sheep breeds in Egypt (Barki, Ossimi, and Rahmani) and Saudi Arabia (Najdi) using polymerase chain reaction (PCR) and sequencing.Materials and methodsBlood samples were collected, and DNA was extracted from 75 animals. A 386 bp fragment in the first intron of the MSTN gene was amplified using PCR. Polymorphic sites were detected using direct sequencing and then correlated with growth traits using a general linear model.ResultsSequence analysis of the first intron of MSTN gene identified six single-nucleotide polymorphisms (SNPs) in the studied breeds. Four mutual SNPs were determined: c.18 G>T, c.241 T>C, c.243 G>A, and c.259 G>T. In addition, two SNPs c.159 A>T and c.173 T>G were monomorphic (AA and TT, respectively) in the Ossimi, Rahmani, and Najdi breeds and polymorphic in the Barki breed. The association analysis revealed that the c.18 G>T and c.241 C>T significantly associated (p<0.05) with birth weight and average daily weight gain, respectively.ConclusionOur results strongly support MSTN as a candidate gene for marker-assisted selection in sheep breeding programs. Furthermore, the identified variants may be considered as putative markers to improve growth traits in sheep.
| S-EPMC7994128 | biostudies-literature
Project description:Recent developments in high-density genotyping and statistical analysis methods that have enabled genome-wide association studies in humans can also be applied to outbred mouse populations. Increased recombination in outbred populations is expected to provide greater mapping resolution than traditional inbred line crosses, improving prospects for identifying the causal genes. We carried out genome-wide association mapping by using 288 mice from a commercially available outbred stock; NMRI mice were genotyped with a high-density single-nucleotide polymorphism array to map loci influencing high-density lipoprotein cholesterol, systolic blood pressure, triglyceride levels, glucose, and urinary albumin-to-creatinine ratios. We found significant associations (P < 10(-5)) with high-density lipoprotein cholesterol and identified Apoa2 and Scarb1, both of which have been previously reported, as candidate genes for these associations. Additional suggestive associations (P < 10(-3)) identified in this study were also concordant with published quantitative trait loci, suggesting that we are sampling from a limited pool of genetic diversity that has already been well characterized. These findings dampen our enthusiasm for currently available commercial outbred stocks as genetic mapping resources and highlight the need for new outbred populations with greater genetic diversity. Despite the lack of novel associations in the NMRI population, our analysis strategy illustrates the utility of methods that could be applied to genome-wide association studies in humans.
| S-EPMC3284324 | biostudies-other
Project description:The application of genomic selection to sheep breeding could lead to substantial increases in profitability of wool production due to the availability of accurate breeding values from single nucleotide polymorphism (SNP) data. Several key traits determine the value of wool and influence a sheep's susceptibility to fleece rot and fly strike. Our aim was to predict genomic estimated breeding values (GEBV) and to compare three methods of combining information across traits to map polymorphisms that affect these traits.GEBV for 5726 Merino and Merino crossbred sheep were calculated using BayesR and genomic best linear unbiased prediction (GBLUP) with real and imputed 510,174 SNPs for 22 traits (at yearling and adult ages) including wool production and quality, and breech conformation traits that are associated with susceptibility to fly strike. Accuracies of these GEBV were assessed using fivefold cross-validation. We also devised and compared three approximate multi-trait analyses to map pleiotropic quantitative trait loci (QTL): a multi-trait genome-wide association study and two multi-trait methods that use the output from BayesR analyses. One BayesR method used local GEBV for each trait, while the other used the posterior probabilities that a SNP had an effect on each trait.BayesR and GBLUP resulted in similar average GEBV accuracies across traits (~0.22). BayesR accuracies were highest for wool yield and fibre diameter (>0.40) and lowest for skin quality and dag score (<0.10). Generally, accuracy was higher for traits with larger reference populations and higher heritability. In total, the three multi-trait analyses identified 206 putative QTL, of which 20 were common to the three analyses. The two BayesR multi-trait approaches mapped QTL in a more defined manner than the multi-trait GWAS. We identified genes with known effects on hair growth (i.e. FGF5, STAT3, KRT86, and ALX4) near SNPs with pleiotropic effects on wool traits.The mean accuracy of genomic prediction across wool traits was around 0.22. The three multi-trait analyses identified 206 putative QTL across the ovine genome. Detailed phenotypic information helped to identify likely candidate genes.
| S-EPMC5558709 | biostudies-other
Project description:Dissecting the genetic architecture of fitness-related traits in wild populations is key to understanding evolution and the mechanisms maintaining adaptive genetic variation. We took advantage of a recently developed genetic linkage map and phenotypic information from wild pedigreed individuals from Ram Mountain, Alberta, Canada, to study the genetic architecture of ecologically important traits (horn volume, length, base circumference and body mass) in bighorn sheep. In addition to estimating sex-specific and cross-sex quantitative genetic parameters, we tested for the presence of quantitative trait loci (QTLs), colocalization of QTLs between bighorn sheep and domestic sheep, and sex × QTL interactions. All traits showed significant additive genetic variance and genetic correlations tended to be positive. Linkage analysis based on 241 microsatellite loci typed in 310 pedigreed animals resulted in no significant and five suggestive QTLs (four for horn dimension on chromosomes 1, 18 and 23, and one for body mass on chromosome 26) using genome-wide significance thresholds (Logarithm of odds (LOD) >3.31 and >1.88, respectively). We also confirmed the presence of a horn dimension QTL in bighorn sheep at the only position known to contain a similar QTL in domestic sheep (on chromosome 10 near the horns locus; nominal P<0.01) and highlighted a number of regions potentially containing weight-related QTLs in both species. As expected for sexually dimorphic traits involved in male-male combat, loci with sex-specific effects were detected. This study lays the foundation for future work on adaptive genetic variation and the evolutionary dynamics of sexually dimorphic traits in bighorn sheep.
| S-EPMC3282393 | biostudies-literature
Project description:BACKGROUND:The detection of regions that affect quantitative traits (QTL), to implement selection assisted by molecular information, remains of particular interest in dairy sheep for which genetic gain is constrained by the high costs of large-scale phenotype and pedigree recording. QTL detection based on the combination of linkage disequilibrium and linkage analysis (LDLA) is the most suitable approach in family-structured populations. The main issue in performing LDLA mapping is the handling of the identity-by-descent (IBD) probability matrix. Here, we propose the use of principal component analysis (PCA) to perform LDLA mapping for milk traits in Sarda dairy sheep. METHODS:A resource population of 3731 ewes belonging to 161 sire families and genotyped with the OvineSNP50 Beadchip was used to map genomic regions that affect five milk traits. The paternally and maternally inherited gametes of genotyped individuals were reconstructed and IBD probabilities between them were defined both at each SNP position and at the genome level. A QTL detection model fitting fixed effects of principal components that summarize IBD probabilities was tested at each SNP position. Genome-wide (GW) significance thresholds were determined by within-trait permutations. RESULTS:PCA resulted in substantial dimensionality reduction, in fact 137 and 32 (on average) principal components were able to capture 99% of the IBD variation at the locus and genome levels, respectively. Overall, 2563 positions exceeded the 0.05 GW significance threshold for at least one trait, which clustered into 75 QTL regions most of which affected more than one trait. The strongest signal was obtained for protein content on Ovis aries (OAR) chromosome 6 and overlapped with the region that harbours the casein gene cluster. Additional interesting positions were identified on OAR4 for fat content and on OAR11 for the three yield traits. CONCLUSIONS:PCA is a good strategy to summarize IBD probabilities. A large number of regions associated to milk traits were identified. The outputs provided by the proposed method are useful for the selection of candidate genes, which need to be further investigated to identify causative mutations or markers in strong LD with them for application in selection programs assisted by molecular information.
| S-EPMC6862840 | biostudies-literature
Project description:Alveolar macrophages function in innate and adaptive immunity, wound healing, and homeostasis in the lungs dependent on tissue-specific gene expression under epigenetic regulation. The functional diversity of tissue resident macrophages, despite their common myeloid lineage, highlights the need to study tissue-specific regulatory elements that control gene expression. Increasing evidence supports the hypothesis that subtle genetic changes alter sheep macrophage response to important production pathogens and zoonoses, for example, viruses like small ruminant lentiviruses and bacteria like Coxiella burnetii. Annotation of transcriptional regulatory elements will aid researchers in identifying genetic mutations of immunological consequence. Here we report the first genome-wide survey of regulatory elements in any sheep immune cell, utilizing alveolar macrophages. We assayed histone modifications and CTCF enrichment by chromatin immunoprecipitation with deep sequencing (ChIP-seq) in two sheep to determine cis-regulatory DNA elements and chromatin domain boundaries that control immunity-related gene expression. Histone modifications included H3K4me3 (denoting active promoters), H3K27ac (active enhancers), H3K4me1 (primed and distal enhancers), and H3K27me3 (broad silencers). In total, we identified 248,674 reproducible regulatory elements, which allowed assignment of putative biological function in macrophages to 12% of the sheep genome. Data exceeded the FAANG and ENCODE standards of 20 million and 45 million useable fragments for narrow and broad marks, respectively. Active elements showed consensus with RNA-seq data and were predictive of gene expression in alveolar macrophages from the publicly available Sheep Gene Expression Atlas. Silencer elements were not enriched for expressed genes, but rather for repressed developmental genes. CTCF enrichment enabled identification of 11,000 chromatin domains with mean size of 258 kb. To our knowledge, this is the first report to use immunoprecipitated CTCF to determine putative topological domains in sheep immune cells. Furthermore, these data will empower phenotype-associated mutation discovery since most causal variants are within regulatory elements.
| S-EPMC7817998 | biostudies-literature
Project description:BackgroundArtificial and natural selection for important economic traits and genetic adaptation of the populations to specific environments have led to the changes on the sheep genome. Recent advances in genome sequencing methods have made it possible to use comparative genomics tools to identify genes under selection for traits of economic interest in domestic animals.ObjectivesIn this study, we compared the genomes of Assaf and Awassi sheep breeds with those of the Cambridge, Romanov and British du cher sheep breeds to explore positive selection signatures for milk traits using nucleotide diversity (Pi) and FST statistical methods.MethodsGenome sequences from fourteen sheep with a mean sequence depth of 9.32X per sample were analysed, and a total of 23 million single nucleotide polymorphisms (SNPs) were called and applied for this study. Genomic clustering of breeds was identified using ADMIXTURE software. The FST and Pi values for each SNP were computed between population A (Assaf and Awassi) and population B (Cambridge, British du cher, and Romanov).ResultsThe results of the PCA grouped two classes for these five dairy sheep breeds. The selection signatures analysis displayed 735 and 515 genes from FST and nucleotide diversity (Pi) statistical methods, respectively. Among all these, 12 genes were shared between the two approaches. The most conspicuous genes were related to milk traits, including ST3GAL1 (the synthesis of oligosacáridos), CSN1S1 (milk protein), CSN2 (milk protein), OSBPL8 (fatty acid traits), SLC35A3 (milk fat and protein percentage), VPS13B (total milk production, fat yield, and protein yield), DPY19L1 (peak yield), CCDC152 (lactation persistency and somatic cell count), NT5DC1 (lactation persistency), P4HTM (test day protein), CYTH4 (FAT Production) and METRNL (somatic cell), U1 (milk traits), U6 (milk traits) and 5S_RRNA (milk traits).ConclusionsThe findings provide new insight into the genetic basis of sheep milk properties and can play a role in designing sheep breeding programs incorporating genomic information.
| S-EPMC9122411 | biostudies-literature