Browsing by Author "Cole, John B."

Now showing 1 - 9 of 9
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    Analyses of inter-individual variations of sperm DNA methylation and their potential implications in cattle
    (Springer Nature, 2019-11-21) Liu, Shuli; Fang, Lingzhao; Zhou, Yang; Santos, Daniel J.A.; Xiang, Ruidong; Daetwyler, Hans D.; Chamberlain, Amanda J.; Cole, John B.; Li, Cong-jun; Yu, Ying; Ma, Li; Zhang, Shengli; Liu, George E.
    DNA methylation has been shown to be involved in many biological processes, including X chromosome inactivation in females, paternal genomic imprinting, and others.
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    Array CGH-based detection of CNV regions and their potential association with reproduction and other economic traits in Holsteins
    (Springer Nature, 2019-03-07) Liu, Mei; Fang, Lingzhao; Liu, Shuli; Pan, Michael G.; Seroussi, Eyal; Cole, John B.; Ma, Li; Chen, Hong; Liu, George E.
    Copy number variations (CNVs) are structural variants consisting of large-scale insertions and deletions of genomic fragments. Exploring CNVs and estimating their effects on phenotypes are useful for genome selection but remain challenging in the livestock.
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    Comparative transcriptome in large-scale human and cattle populations
    (Springer Nature, 2022-08-22) Yao, Yuelin; Liu, Shuli; Xia, Charley; Gao, Yahui; Pan, Zhangyuan; Canela-Xandri, Oriol; Khamseh, Ava; Rawlik, Konrad; Wang, Sheng; Li, Bingjie; Zhang, Yi; Pairo-Castineira, Erola; D’Mellow, Kenton; Li, Xiujin; Yan, Ze; Li, Cong-jun; Yu, Ying; Zhang, Shengli; Ma, Li; Cole, John B.; Ross, Pablo J.; Zhou, Huaijun; Haley, Chris; Liu, George E.; Fang, Lingzhao; Tenesa, Albert
    Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.
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    Comparative whole genome DNA methylation profiling across cattle tissues reveals global and tissue-specific methylation patterns
    (Springer Nature, 2020-07-06) Zhou, Yang; Liu, Shuli; Hu, Yan; Fang, Lingzhao; Gao, Yahui; Xia, Han; Schroeder, Steven G.; Rosen, Benjamin D.; Connor, Erin E.; Li, Cong-jun; Baldwin, Ransom L.; Cole, John B.; Van Tassell, Curtis P.; Yang, Liguo; Ma, Li; Liu, George E.
    Efforts to improve animal health, and understand genetic bases for production, may benefit from a comprehensive analysis of animal genomes and epigenomes. Although DNA methylation has been well studied in humans and other model species, its distribution patterns and regulatory impacts in cattle are still largely unknown. Here, we present the largest collection of cattle DNA methylation epigenomic data to date. Using Holstein cattle, we generated 29 whole genome bisulfite sequencing (WGBS) datasets for 16 tissues, 47 corresponding RNA-seq datasets, and 2 whole genome sequencing datasets. We did read mapping and DNA methylation calling based on two different cattle assemblies, demonstrating the high quality of the long-read-based assembly markedly improved DNA methylation results. We observed large differences across cattle tissues in the methylation patterns of global CpG sites, partially methylated domains (PMDs), hypomethylated regions (HMRs), CG islands (CGIs), and common repeats. We detected that each tissue had a distinct set of PMDs, which showed tissue-specific patterns. Similar to human PMD, cattle PMDs were often linked to a general decrease of gene expression and a decrease in active histone marks and related to long-range chromatin organizations, like topologically associated domains (TADs). We tested a classification of the HMRs based on their distributions relative to transcription start sites (TSSs) and detected tissue-specific TSS-HMRs and genes that showed strong tissue effects. When performing cross-species comparisons of paired genes (two opposite strand genes with their TSS located in the same HMR), we found out they were more consistently co-expressed among human, mouse, sheep, goat, yak, pig, and chicken, but showed lower consistent ratios in more divergent species. We further used these WGBS data to detect 50,023 experimentally supported CGIs across bovine tissues and found that they might function as a guard against C-to-T mutations for TSS-HMRs. Although common repeats were often heavily methylated, some young Bov-A2 repeats were hypomethylated in sperm and could affect the promoter structures by exposing potential transcription factor binding sites. This study provides a comprehensive resource for bovine epigenomic research and enables new discoveries about DNA methylation and its role in complex traits.
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    Dissection of additive, dominance, and imprinting effects for production and reproduction traits in Holstein cattle
    (Springer Nature, 2017-05-30) Jiang, Jicai; Shen, Botong; O’Connell, Jeffrey R.; VanRaden, Paul M.; Cole, John B.; Ma, Li
    Although genome-wide association and genomic selection studies have primarily focused on additive effects, dominance and imprinting effects play an important role in mammalian biology and development. The degree to which these non-additive genetic effects contribute to phenotypic variation and whether QTL acting in a non-additive manner can be detected in genetic association studies remain controversial. To empirically answer these questions, we analyzed a large cattle dataset that consisted of 42,701 genotyped Holstein cows with genotyped parents and phenotypic records for eight production and reproduction traits. SNP genotypes were phased in pedigree to determine the parent-of-origin of alleles, and a three-component GREML was applied to obtain variance decomposition for additive, dominance, and imprinting effects. The results showed a significant non-zero contribution from dominance to production traits but not to reproduction traits. Imprinting effects significantly contributed to both production and reproduction traits. Interestingly, imprinting effects contributed more to reproduction traits than to production traits. Using GWAS and imputation-based fine-mapping analyses, we identified and validated a dominance association signal with milk yield near RUNX2, a candidate gene that has been associated with milk production in mice. When adding non-additive effects into the prediction models, however, we observed little or no increase in prediction accuracy for the eight traits analyzed. Collectively, our results suggested that non-additive effects contributed a non-negligible amount (more for reproduction traits) to the total genetic variance of complex traits in cattle, and detection of QTLs with non-additive effect is possible in GWAS using a large dataset.
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    Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human
    (Springer Nature, 2020-07-03) Liu, Shuli; Yu, Ying; Zhang, Shengli; Cole, John B.; Tenesa, Albert
    Lack 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. We 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. Collectively, 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.
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    Genome changes due to artificial selection in U.S. Holstein cattle
    (Springer Nature, 2019-02-11) Ma, Li; Sonstegard, Tad S.; Cole, John B.; VanTassell, Curtis P.; Wiggans, George R.; Crooker, Brian A.; Tan, Cheng; Prakapenka, Dzianis; Liu, George E.; Da, Yang
    The availability of a unique unselected Holstein line since 1964 provided a direct comparison between selected and unselected Holstein genomes whereas large Holstein samples provided unprecedented statistical power for identifying high-confidence SNP effects. Utilizing these unique resources, we aimed to identify genome changes affected by selection since 1964.
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    Genome-wide recombination map construction from single sperm sequencing in cattle
    (Springer Nature, 2022-03-05) Yang, Liu; Gao, Yahui; Li, Mingxun; Park, Ki-Eun; Liu, Shuli; Kang, Xiaolong; Liu, Mei; Oswalt, Adam; Fang, Lingzhao; Telugu, Bhanu P.; Sattler, Charles G.; Li, Cong-jun; Cole, John B.; Seroussi, Eyal; Xu, Lingyang; Yang, Lv; Zhou, Yang; Li, Li; Zhang, Hongping; Rosen, Benjamin D.; Van Tassell, Curtis P.; Ma, Li; Liu, George E.
    Meiotic recombination is one of the important phenomena contributing to gamete genome diversity. However, except for human and a few model organisms, it is not well studied in livestock, including cattle. To investigate their distributions in the cattle sperm genome, we sequenced 143 single sperms from two Holstein bulls. We mapped meiotic recombination events at high resolution based on phased heterozygous single nucleotide polymorphism (SNP). In the absence of evolutionary selection pressure in fertilization and survival, recombination events in sperm are enriched near distal chromosomal ends, revealing that such a pattern is intrinsic to the molecular mechanism of meiosis. Furthermore, we further validated these findings in single sperms with results derived from sequencing its family trio of diploid genomes and our previous studies of recombination in cattle. To our knowledge, this is the first large-scale single sperm whole-genome sequencing effort in livestock, which provided useful information for future studies of recombination, genome instability, and male infertility.
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    GWAS and fine-mapping of livability and six disease traits in Holstein cattle
    (Springer Nature, 2020-01-13) Freebern, Ellen; Santos, Daniel J. A.; Fang, Lingzhao; Jiang, Jicai; Parker Gaddis, Kristen L.; Liu, George E.; VanRaden, Paul M.; Maltecca, Christian; Cole, John B.; Ma, Li
    Health traits are of significant economic importance to the dairy industry due to their effects on milk production and associated treatment costs. Genome-wide association studies (GWAS) provide a means to identify associated genomic variants and thus reveal insights into the genetic architecture of complex traits and diseases. The objective of this study is to investigate the genetic basis of seven health traits in dairy cattle and to identify potential candidate genes associated with cattle health using GWAS, fine mapping, and analyses of multi-tissue transcriptome data.