College of Agriculture & Natural Resources
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The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
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Item 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, AlbertCross-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.Item 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.Item Towards the detection of copy number variation from single sperm sequencing in cattle(Springer Nature, 2022-03-17) Yang, Liu; Gao, Yahui; Oswalt, Adam; Fang, Lingzhao; Boschiero, Clarissa; Neupane, Mahesh; Sattler, Charles G.; Li, Cong-jun; Seroussi, Eyal; Xu, Lingyang; Yang, Lv; Li, Li; Zhang, Hongping; Rosen, Benjamin D.; Van Tassell, Curtis P.; Zhou, Yang; Ma, Li; Liu, George E.Copy number variation (CNV) has been routinely studied using bulk-cell sequencing. However, CNV is not well studied on the single-cell level except for humans and a few model organisms. We sequenced 143 single sperms of two Holstein bulls, from which we predicted CNV events using 14 single sperms with deep sequencing. We then compared the CNV results derived from single sperms with the bulk-cell sequencing of one bull’s family trio of diploid genomes. As a known CNV hotspot, segmental duplications were also predicted using the bovine ARS-UCD1.2 genome. Although the trio CNVs validated only some single sperm CNVs, they still showed a distal chromosomal distribution pattern and significant associations with segmental duplications and satellite repeats. Our preliminary results pointed out future research directions and highlighted the importance of uniform whole genome amplification, deep sequence coverage, and dedicated software pipelines for CNV detection using single cell sequencing data.Item 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.Item Functional annotation of the cattle genome through systematic discovery and characterization of chromatin states and butyrate-induced variations(Springer Nature, 2019-08-16) Fang, Lingzhao; Liu, Shuli; Liu, Mei; Kang, Xiaolong; Lin, Shudai; Li, Bingjie; Connor, Erin E.; Baldwin, Ransom L. VI; Tenesa, Albert; Ma, Li; Liu, George E.; Li, Cong-junThe functional annotation of genomes, including chromatin accessibility and modifications, is important for understanding and effectively utilizing the increased amount of genome sequences reported. However, while such annotation has been well explored in a diverse set of tissues and cell types in human and model organisms, relatively little data are available for livestock genomes, hindering our understanding of complex trait variation, domestication, and adaptive evolution. Here, we present the first complete global landscape of regulatory elements in cattle and explore the dynamics of chromatin states in rumen epithelial cells induced by the rumen developmental regulator—butyrate.Item 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.Item 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, LiHealth 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.Item 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.Item Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle(Springer Nature, 2020-07-17) Yan, Ze; Huang, Hetian; Freebern, Ellen; Santos, Daniel J. A.; Dai, Dongmei; Si, Jingfang; Ma, Chong; Cao, Jie; Guo, Gang; Liu, George E.; Ma, Li; Fang, Lingzhao; Zhang, YiKetosis is a common metabolic disease during the transition period in dairy cattle, resulting in long-term economic loss to the dairy industry worldwide. While genetic selection of resistance to ketosis has been adopted by many countries, the genetic and biological basis underlying ketosis is poorly understood. We collected a total of 24 blood samples from 12 Holstein cows, including 4 healthy and 8 ketosis-diagnosed ones, before (2 weeks) and after (5 days) calving, respectively. We then generated RNA-Sequencing (RNA-Seq) data and seven blood biochemical indicators (bio-indicators) from leukocytes and plasma in each of these samples, respectively. By employing a weighted gene co-expression network analysis (WGCNA), we detected that 4 out of 16 gene-modules, which were significantly engaged in lipid metabolism and immune responses, were transcriptionally (FDR < 0.05) correlated with postpartum ketosis and several bio-indicators (e.g., high-density lipoprotein and low-density lipoprotein). By conducting genome-wide association signal (GWAS) enrichment analysis among six common health traits (ketosis, mastitis, displaced abomasum, metritis, hypocalcemia and livability), we found that 4 out of 16 modules were genetically (FDR < 0.05) associated with ketosis, among which three were correlated with postpartum ketosis based on WGCNA. We further identified five candidate genes for ketosis, including GRINA, MAF1, MAFA, C14H8orf82 and RECQL4. Our phenome-wide association analysis (Phe-WAS) demonstrated that human orthologues of these candidate genes were also significantly associated with many metabolic, endocrine, and immune traits in humans. For instance, MAFA, which is involved in insulin secretion, glucose response, and transcriptional regulation, showed a significantly higher association with metabolic and endocrine traits compared to other types of traits in humans. In summary, our study provides novel insights into the molecular mechanism underlying ketosis in cattle, and highlights that an integrative analysis of omics data and cross-species mapping are promising for illustrating the genetic architecture underpinning complex traits.