Dataset Information

Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.

ABSTRACT: By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., CCDC88C) for male fertility, brain (e.g., TRIM46 and RAB6A) for milk production, and multiple growth-related tissues (e.g., FGF6 and CCND2) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.

SUBMITTER: Fang L

PROVIDER: S-EPMC7263193 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.

Fang Lingzhao L Cai Wentao W Liu Shuli S Canela-Xandri Oriol O Gao Yahui Y Jiang Jicai J Rawlik Konrad K Li Bingjie B Schroeder Steven G SG Rosen Benjamin D BD Li Cong-Jun CJ Sonstegard Tad S TS Alexander Leeson J LJ Van Tassell Curtis P CP VanRaden Paul M PM Cole John B JB Yu Ying Y Zhang Shengli S Tenesa Albert A Ma Li L Liu George E GE

Genome research 20200518 5

By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide asso ...[more]

PMID: 32424068

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Project description:BackgroundLack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.ResultsWe cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant biology. Through integrating cross-mapped tissue-specific histone marks with large-scale GWAS and selection signature results, we for the first time detected relevant tissues and cell types for 45 economically important traits and artificial selection in cattle. For instance, immune tissues are significantly associated with health and reproduction traits, multiple tissues for milk production and body conformation traits (reflecting their highly polygenic architecture), and thyroid for the different selection between beef and dairy cattle. Similarly, we detected relevant tissues for 58 complex traits and diseases in humans and observed that immune and fertility traits in humans significantly correlated with those in cattle in terms of relevant tissues, which facilitated the identification of causal genes for such traits. For instance, PIK3CG, a gene highly specifically expressed in mononuclear cells, was significantly associated with both age-at-menopause in human and daughter-still-birth in cattle. ICAM, a T cell-specific gene, was significantly associated with both allergic diseases in human and metritis in cattle.ConclusionCollectively, our results highlighted that comparative epigenomics in conjunction with GWAS and selection signature analyses could provide biological insights into the phenotypic variation and adaptive evolution. Cattle may serve as a model for human complex traits, by providing additional information beyond laboratory model organisms, particularly when more novel phenotypes become available in the near future.

Project description:BackgroundNutrient acquisition and allocation integrate foraging and life-history traits in insects. To compensate for the lack of a particular nutrient at different life stages, insects may acquire these through supplementary feeding, for example, on vertebrate secretions, in a process known as puddling. The mosquito Anopheles arabiensis emerges undernourished, and as such, requires nutrients for both metabolism and reproduction. The purpose of this study was to assess whether An. arabiensis engage in puddling on cattle urine to obtain nutrients to improve life history traits.MethodsTo determine whether An. arabiensis are attracted to the odour of fresh, 24 h, 72 h and 168 h aged cattle urine, host-seeking and blood-fed (48 h post-blood meal) females were assayed in a Y-tube olfactometer, and gravid females assessed in an oviposition assay. Combined chemical and electrophysiological analyses were subsequently used to identify the bioactive compounds in all four age classes of cattle urine. Synthetic blends of bioactive compounds were evaluated in both Y-tube and field assays. To investigate the cattle urine, and its main nitrogenous compound, urea, as a potential supplementary diet for malaria vectors, feeding parameters and life history traits were measured. The proportion of female mosquitoes and the amount of cattle urine and urea imbibed, were assessed. Following feeding, females were evaluated for survival, tethered flight and reproduction.ResultsHost-seeking and blood-fed An. arabiensis were attracted to the natural and synthetic odour of fresh and aged cattle urine in both laboratory and field studies. Gravid females were indifferent in their response to cattle urine presence at oviposition sites. Host-seeking and blood-fed females actively imbibed cattle urine and urea, and allocated these resources according to life history trade-offs to flight, survival or reproduction, as a function of physiological state.ConclusionsAnopheles arabiensis acquire and allocate cattle urine to improve life history traits. Supplementary feeding on cattle urine affects vectorial capacity directly by increasing daily survival and vector density, as well as indirectly by altering flight activity, and thus should be considered in future models.

Project description:Background The search for quantitative trait loci (QTL) affecting traits of interest in mammals is frequently limited to autosomes, with the X chromosome excluded because of its hemizygosity in males. This study aimed to assess the importance of the X chromosome in the genetic determinism of 11 complex traits related to milk production, milk composition, mastitis resistance, fertility, and stature in 236,496 cows from three major French dairy breeds (Holstein, Montbéliarde, and Normande) and three breeds of regional importance (Abondance, Tarentaise, and Vosgienne). Results Estimates of the proportions of heritability due to autosomes and X chromosome (h²X) were consistent among breeds. On average over the 11 traits, h²X=0.008 and the X chromosome explained ~ 3.5% of total genetic variance. GWAS was performed within-breed at the sequence level (~ 200,000 genetic variants) and then combined in a meta-analysis. QTL were identified for most breeds and traits analyzed, with the exception of Tarentaise and Vosgienne and two fertility traits. Overall, 3, 74, 59, and 71 QTL were identified in Abondance, Montbéliarde, Normande, and Holstein, respectively, and most were associated with the most-heritable traits (milk traits and stature). The meta-analyses, which assessed a total of 157 QTL for the different traits, highlighted new QTL and refined the positions of some QTL found in the within-breed analyses. Altogether, our analyses identified a number of functional candidate genes, with the most notable being GPC3, MBNL3, HS6ST2, and DMD for dairy traits; TMEM164, ACSL4, ENOX2, HTR2C, AMOT, and IRAK1 for udder health; MAMLD1 and COL4A6 for fertility; and NRK, ESX1, GPR50, GPC3, and GPC4 for stature. Conclusions This study demonstrates the importance of the X chromosome in the genetic determinism of complex traits in dairy cattle and highlights new functional candidate genes and variants for these traits. These results could potentially be extended to other species as many X-linked genes are shared among mammals. Supplementary Information The online version contains supplementary material available at 10.1186/s12864-023-09438-7.

Project description:BackgroundA better understanding of the genetic architecture underlying complex traits (e.g., the distribution of causal variants and their effects) may aid in the genomic prediction. Here, we hypothesized that the genomic variants of complex traits might be enriched in a subset of genomic regions defined by genes grouped on the basis of "Gene Ontology" (GO), and that incorporating this independent biological information into genomic prediction models might improve their predictive ability.ResultsFour complex traits (i.e., milk, fat and protein yields, and mastitis) together with imputed sequence variants in Holstein (HOL) and Jersey (JER) cattle were analysed. We first carried out a post-GWAS analysis in a HOL training population to assess the degree of enrichment of the association signals in the gene regions defined by each GO term. We then extended the genomic best linear unbiased prediction model (GBLUP) to a genomic feature BLUP (GFBLUP) model, including an additional genomic effect quantifying the joint effect of a group of variants located in a genomic feature. The GBLUP model using a single random effect assumes that all genomic variants contribute to the genomic relationship equally, whereas GFBLUP attributes different weights to the individual genomic relationships in the prediction equation based on the estimated genomic parameters. Our results demonstrate that the immune-relevant GO terms were more associated with mastitis than milk production, and several biologically meaningful GO terms improved the prediction accuracy with GFBLUP for the four traits, as compared with GBLUP. The improvement of the genomic prediction between breeds (the average increase across the four traits was 0.161) was more apparent than that it was within the HOL (the average increase across the four traits was 0.020).ConclusionsOur genomic feature modelling approaches provide a framework to simultaneously explore the genetic architecture and genomic prediction of complex traits by taking advantage of independent biological knowledge.

Dataset Information

Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.

Publications

Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.

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