Progress 09/01/13 to 08/31/18
Outputs
Target Audience:Farmers, scientists, livestock industries and policy planners who need improve animal health and production based on genome-enabled animal selection. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?1. Reuben Anderson, technician, contributed to qPCR, NGS, and DNA methylation validation 2. Shuli Liu, Ph. D. student, contributed to DMR and DMC call algorithms 3. Mei Liu, Ph. D. student, contributed to other epigenetic markers 4. Jicai Jiang, Ph. D. student, contributed to GWAS analyses 5. Lingzhao Fang, Postdoc, contributed to post-GWAS analyse 6. Shudai Lin, Postdoc, contributed to RNA-seq 7. Xiaolong Kang, Postdoc, contributed to other epigenetic markers 8. Yang Zhou, Visiting Scholar, contributed to DMR and DMC call algorithms How have the results been disseminated to communities of interest?1. Invited presentation, Liu, G.E. et al. "Genome-wide sequencing and comparative profiling of cattle sperm DNAmethylome reveals its hypomethylated patterns" at Cattle/Sheep/Goat Workshop of Plant and Animal Genome Conference, San Diego, CA, January 14, 2018. 2. Invited presentation, Liu, M. et al. "Diversity of copy number variation in the worldwide goat population at Cattle/Sheep/Goat Workshop of Plant and Animal Genome Conference, San Diego, CA, January 14, 2018. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
For objective 1: We have generated sperm DNA methylome for 20 representative dairy bulls with extreme fertility phenotypes (i.e., PredictedTransmitting Ability - PTA) by using the whole genome bisulfite sequencing (WGBS) technology. We also sequenced additional four sperm DNA methylome from two individual pairs at young and aged stages, to study the aging effects on sperm DNA methylation. In general, we found that the methylation patterns were highly conserved among all the studied samples with the Pearson correlations ranging from 0.91 to 0.96. Integrative analysis of sperm DNA methylome with other data sources (e.g., genome wide association studies - GWAS and genomic evolution features) provided novel insights in the genetic and biological basis underlying male fertility traits, as well as contributed to the better understanding of epigenome evolution. For objective 2: By comparing sperm methylomes among human, mouse and cattle, we studied the epigenome evolution and prioritized GWAS signals of 35 and 60 complex phenotypes in cattle and human, respectively. We observed that genomic regions with differential DNA methylation levels were enriched for GWAS signals across multiple complex traits in human and cattle. For instance, genes with human-specific hypomethylated promoters (e.g., FOXP2 and HYDIN) were enriched for brain-related traits, while genes with cattle-specific hypomethylated promoters (e.g., LDHB and DGAT2) mainly participated in lipid storage and metabolism. We further validated these findings by integrating DNA methylation with other data sources, including sperm-retained nucleosome, histone modifications, preimplantation transcriptome, and tissue proteome, as well as several sequence evolutionary features (e.g., mutation rates, recombination rates and selection signatures). In addition, we investigated that DNA methylation alterations in sperm induced by aging and sire-conception-rate (SCR) impacted male fertility in cattle. For instance, we found genes (e.g., HOX gene clusters and microRNAs) located in dynamic hypomethylated regions (HMRs) and partially methylated domains (PMDs) were significantly involved in the embryonic development. We demonstrated that genomic regions gained methylation rather than those lost methylation during aging and in animals with low-SCR were significantly and selectively enriched for GWAS signals of male fertility traits. In summary, our results demonstrate importance roles of epigenome evolution in shaping the genetic architecture underlying complex phenotypes, hence enhance signal prioritization in GWAS and provide valuable information for human neurological disorders and livestock genetic improvement. For objective 3: We studied the paternal genetic and epigenetic influences on gestation length (GL) in dairy cattle. By conducting GWAS and gene fine-mapping analyses, we detected 25 paternal candidate genes (e.g., HSF1 and MYH10) associated with GL. We demonstrated that GWAS signals of GL were significantly enriched in biological pathways that were related to the embryonic development, and significantly (P < 0.05) enriched in differentially methylated regions (DMRs) in sperm samples that were associated with high and low GL. We provided the genome, epigenome, transcriptome, and selection evidence implicating the ZNF613 gene as a strong candidate gene for GL. From thousands of candidate DMRs, we selected approximately 40 regions that were associated with SCR and validated them in a large sample collection by using Bisulfite Sequencing. Theseresults will facilitate the design of a prototype DNA methylation array for a quickly detection of DNA methylation status of trait-relevant regions in a very large population. By integrating these epigenomic information with genotype data, this project should help to improve genomic prediction for many complex economic traits in dairy cattle in the future.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Zhou, Y., Connor, E.E., Bickhart, D.M., Li, C., Baldwin, R.L., Schroeder, S.G., Rosen, B.D., Yang, L., Van Tassell, C.P., Liu, G.E. 2018. Comparative whole genome DNA methylation profiling of cattle sperm and somatic tissues reveals striking hypomethylated patterns in sperm. Gigascience. 7(5). doi: 10.1093/gigascience/giy039. PubMed PMID: 29635292; PubMed Central PMCID: PMC5928411.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2018
Citation:
Fang, L., Zhou, Y., Liu, S., Jiang, J., Bickhart, D.M., Null, D.J., Li, B., Schroeder, G.S., Rosen, B.D., Cole, J.B., Van Tassell, C.P., Ma, L., Liu, G.E. 2018. Comparative analysis of sperm DNA methylome among human, mouse and cattle provides insights into epigenomic evolution and complex traits. Epigenetics. Under Review.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2018
Citation:
Fang, L., Zhou, Y., Liu, S., Jiang, J., Bickhart, D.M., Null, D.J., Li, B., Schroeder, G.S., Rosen, B.D., Cole, J.B., Van Tassell, C.P., Ma, L., Liu, G.E. 2018. Integrating sperm methylome with genome-wide association study to understand male fertility in cattle. BMC Genomics. Under Review.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2018
Citation:
Fang, L., Jiang, J., Li, B., Zhou, Y., Freebern, E. Van Raden, P.M., Cole, J.B., Liu, G.E., Ma, L. 2018. Paternal genetic and epigenetic contributions to gestation length in cattle. Communications Biology. Under Review.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Kang, X., Liu, A., Liu, G.E. 2018. Application of multi-omics in single cells. Ann Biotechnol. 2: 1007. https://meddocsonline.org/annals-of-biotechnology/Application-of-multi-omics-in-single-cells.pdf.
- Type:
Book Chapters
Status:
Accepted
Year Published:
2019
Citation:
Lin, S., Fang, L., Liu, G., Li, C. 2019. Epigenetics and Heritable Phenotypic Variations in livestock. Chapter 15, Transgenerational Epigenetics, 2nd edition, Tollefsbol T. ( Editor), Elsevier
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Liu, M., Zhou, Y., Rosen, B.D., Van Tassell, C.P., Stella, A., Tosser-Klopp, G., Rupp, R., Palhi�re, I., Colli, L., Sayre, B., Crepaldi, P., Fang, L., M�sz�ros, G., Chen, H., Liu, G.E., ADAPTmap Consortium. 2018. Diversity of copy number variation in the worldwide goat population. Heredity (Edinb). doi: 10.1038/s41437-018-0150-6. [Epub ahead of print] PubMed PMID: 30401973.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Li, W., Bickhart, D.M., Ramunno, L., Iamartino, D., Williams, J.L., Liu, G.E. 2018. Genomic structural differences between cattle and River Buffalo identified through comparative genomic and transcriptomic analysis. Data Brief. 10;19:236-239. doi: 10.1016/j.dib.2018.05.015. eCollection 2018 Aug. PubMed PMID: 29892639; PubMed Central PMCID: PMC5993156.
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Progress 09/01/16 to 08/31/17
Outputs
Target Audience:Farmers, scientists, livestock industries and policy planners who need improve animal health and production based on genome-enabled animal selection. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?1. Reuben Anderson, technician, contributed to qPCR, NGS, and DNA methylation validation 2. Alexander Dimtchev, technician, contributed to qPCR and DNA methylation validation 3. Yang Zhou, Ph. D. student, contributed to DMR and DMC call algorithms 3. Jicai Jiang, Ph. D. student, contributed to GWAS analyses 4. Lingzhao Fang, Postdoc, contributed to post-GWAS analyse How have the results been disseminated to communities of interest?1. Invited presentation, Liu, G.E. et al. "Systematic profiling of bovine short tandem repeats using whole genome sequencing data" at Cattle/Sheep/Goat Workshop of Plant and Animal Genome Conference, San Diego, CA, January 15, 2017. 2. Invited presentation, Liu, G.E. et al. "Sperm DNA methylome and its impacts on male fertility in dairy cattle" at China Agricultural University, Beijing, China, August 15, 2017. What do you plan to do during the next reporting period to accomplish the goals?Since the methylation patterns of all the tested sperm samples were highly conserved, we detected only a few dozens of high-confidence DMRs (Results from Objective 1 and Objective 2). For Objective 3, we will continue to identify functional DMRs associated with sire conception rate. However, developing high-throughput DNA methylation assays for semen quality control will be currently limited by the available detected DMRs. Teaming up with Illumina, other universities and FAANG projects, we are actively pursuing to design bovine DNA methylation arrays based on Illumina's Infinium platform. The long-term goal is to develop an array-based tools to measure DNA methylation with highly informative probes uniformly distributed across the entire genome of major cattle breed types, empowering applications such as genome-wide enabled selection, identification of quantitative trait loci, evaluation of genetic merit of individuals, and comparative genetic studies.
Impacts
What was accomplished under these goals?
For objectives 1, we have generated 20 representative sperm DNA methylome of dairy cattle with extreme sire conception rates (SCR) using the bisulfite sequencing method (MethylC-seq). We also included additional four sperm DNA methylome from two bulls with different collection ages to test age effects on sperm DNA methylation. In general, we found the methylation patterns of all the tested sperm samples were highly conserved (correlation range: 0.91-0.96). For objective 2, using q-values < 1e-5 (SLIM-corrected) and meth.diff > 20, we have detected 2,707 and 4,182 differentially methylated regions (1kb window) associated with SCR and age, respectively. We have integrated the sperm DNA methylome with sequence-based genome-wide association studies (GWAS) for 38 economically important complex traits, including 15, 6 and 17 reproduction, production and type traits, respectively, and found that the sperm methylated regions were enriched with GWAS signals for most traits by using both permutation and hypergeometric tests. We also found that both SCR- and age-associated DMRs were enriched with reproduction traits much more than production and type traits. More interestingly, the hyper-methylated DMRs for both SCR (low vs. high) and age (age vs. young) were enriched with reproduction traits much more than the hypo-methylated DMRs. A total of 37 hyper-methylated DMRs (meth.diff > 20) were shared between SCR and age groups, which were located within 11 genes, including PALM2, ATP5B, PTPRC, SERPINB1, TTC17, ZNF704, SLC25A48, DNAH7, GRIK1, POLR2K, and SLC9B2. For objective 3, we further detected DMC in the above DMR regions for both SCR and age. We chose the top DMC in each DMR as the candidates to be confirmed in a larger population. The resultant DMC could be used as additional markers for animal selection for reproduction traits.
Publications
- Type:
Journal Articles
Status:
Accepted
Year Published:
2017
Citation:
Utsunomiya, Y., Milanesi, M., Utsunomiya, A., Torrecilha, R., Kim, E. Silva, M., Do Carmo, A.S., Carvalheiro, R., De Rezende, N.H., Padula, R., Sussai, T., Zavarez, L.B., Cipriano, R.S., Caminhas, M., Hambrecht, G., Colli, L., Eufemi, E., Ajmone-Marsan, P., Buora, M., Liu, G.E., Bickhart, D.M., Van Tassell, C.P., Solkner, J., Sonstegard, T.S., Garcia, J.F. 2017. A haplotype spanning PLAG1 contributed to stature recovery in modern cattle. Scientific Reports. In Press.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2017
Citation:
Liu, S., Cai, W., Yin, H., Liu, A., Li, Y. Wang, Y., Liu, G.E., Yu, Y., Zhang, S. 2017. Genome-scale analysis of sperm DNA methylation in monozygotic twin seed bulls revealing methylation target genes with reproductive discordance. BMC Genomics. Under Review.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2017
Citation:
Zhou, Y., Connor, E.E., Bickhart, D.M., Li, C., Baldwin, R.L., Schroeder, S.G., Rosen, B.D., Yang, L., Van Tassell, C.P., Liu, G.E. 2017. Genome-wide sequencing and comparative profiling of cattle sperm DNA methylome reveals its hypomethylated patterns GigaScience. Under Review.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Xu, L., Hassl, R.J., Sun, J., Zhou, Y., Bickhart, D.M., Song, J., Sonstegard, T.S., Van Tassell, C.P., Lewin, H.A., Liu, G.E. 2017. Systematic Profiling of Short Tandem Repeats in the Cattle Genome. Genome Biol Evol. 9(1):20-31.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Bickhart, D.M., Rosen, B.D., Koren , S., Sayre, B.L., Hastie, A.R., Chan, S., Lee, J., Lam, E.T., Liachko, I., Sullivan, S.T., Burton, J.N., Huson, H.J., Kelley, C. M., Hutchison, J.L., Zhou, Y., Sun, J., Crisa, A., Ponce De Leon, F.A., Schwarts, J.C., Hammond, J.A., Schroeder, S.G., Liu, G.E., Dunham, M., Shendure, J., Sonstegard, T.S., Phillippy, A., Van Tassell, C.P. , Smith, T.P. 2017. Single-molecule sequencing and conformational capture enable de novo mammalian reference genomes. Nat Genet. 49(4):643-650.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2107
Citation:
Zhou, Y., Shen, B., Jiang, J., Padhi, A., Park, K., Telugu, B.P., Chen, H., Cole, J.B., Liu, G.E., Ma, L. 2017. Construction of PRDM9 allele-specific recombination maps in cattle using large-scale pedigree analysis and genome-wide single sperm genomics. 2017. DNA Research. In Press.
- Type:
Journal Articles
Status:
Accepted
Year Published:
2017
Citation:
Zhou, Y., Li, M., Hu, X., Cai, H., Liu, M., Sun, Y., Huang, Y., Dang, R., Lan, X., Lei, C., Liu, G.E., Li, C., and Chen, H. 2017. Characterization of candidate genes for bovine adipogenesis reveals differences of TUSC5 isoforms caused by novel alternative splicing. Oncotarget. In Press.
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Progress 09/01/15 to 08/31/16
Outputs
Target Audience:Farmers, scientists, livestock industries and policy planners who need improve animal health and production based on genome-enabled animal selection. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Teach and mentor 1 postdoc, 1 graduate student and 2 technicians. 1. El HayPostdoc, contributed to DNA methylation callalgorithms 2. Yang Zhou, Ph.D. student, contributed to DNA methylation call algorithms and data analyses 3. Alexander Dimtchev, technician, contributed to PCR validation of DNA methylation results 4. Reuben Anderson, technician, contributed to PCR validation of DNA methylation results How have the results been disseminated to communities of interest?1. Poster presentation, Liu, G.E. et al. "Sperm DNA methylome and its impacts on male fertility in dairy cattle" at the Annual USDA NIFA Animal Reproduction Project Director Meeting, San Juan, Puerto Rico, July 15, 2016. 2. Poster presentation, Liu, G.E. " Initial analysis of sperm DNA methylome in Holstein bulls using whole genome bisulfite sequenicng" at 35th International Society for Animal Genetics Conference, Salt Lake City, Utah, July 23-27, 2016. 3. Plenary talk, Liu G.E. "Genomic variations and their impacts in the cattle genome" at the 18th Chinese National Conference on Animal Genetics and Breeding, Nanchang, Jiangxi, China, November 13-16, 2015 What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We generated 20 sperm DNA methylomes using the bisulfite sequencing method (MethylC-seq or BS-seq). We sequenced 20 representative dairy cattle with extreme sire conception rates, as well as proper controls for the aging effects. For these animals, we generated 60-100Gb of paired reads with mapping rates ranging from 60-85%. We are in the process of evaluating functional impacts of differentially methylated regions (DMR) on genomic features including functional genes, control elements, SNPs and common repeats.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Zhou, Y., L. Xu, D. M. Bickhart, E. A. Hay, S. G. Schroeder, E. E. Connor, L. J. Alexander, T. S. Sonstegard, C. P. Van Tassel, H. Chen, and G. E. Liu. 2016. Reduced representation bisulphite sequencing of ten bovine somatic tissues reveals DNA methylation patterns and their impacts on gene expression. BMC Genomics. 17:779.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Zhou, Y., L. Xu, D. M. Bickhart, E. A. Hay, S. G. Schroeder, E. E. Connor, L. J. Alexander, T. S. Sonstegard, C. P. Van Tassel, H. Chen, and G. E. Liu. 2016. Reduced Representation Bisulphite Sequencing of the Cattle Genome Reveals DNA Methylation Patterning. Plant and Animal Genome Conference XXIV, San Diego, CA, January 12, 2016. W021 and P0514.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu, G.E. et al. "Sperm DNA methylome and its impacts on male fertility in dairy cattle" at the Annual USDA NIFA Animal Reproduction Project Director Meeting, San Diego, CA, July 15, 2016.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Liu, G.E. et al. "Initial analysis of sperm DNA methylome in Holstein bulls using whole genome bisulfide sequenicng" at the 35th International Society for Animal Genetics Conference, July 23-27, 2016, Salt Lake City, Utah. P2009.
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Progress 09/01/14 to 08/31/15
Outputs
Target Audience:Farmers, scientists, livestock industries and policy planners who need improve animal health and production based on genome-enabled animal selection. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Teach and mentor 1 postdoc, 1 graduate student and 2 technicians. 1. Lingyang Xu, Postdoc, contributed to DNA methylation call algorithms 2. Yang Zhou, Ph.D. student, contributed to DNA methylation call algorithms and data analyses 3. Alexander Dimtchev, technician, contributed to PCR validation of DNA methylation results 4. Reuben Anderson, technician, contributed to PCR validation of DNA methylation results How have the results been disseminated to communities of interest?1. Poster presentation, Liu, G.E. et al. "Sperm DNA methylome and its impacts on male fertility in dairy cattle" at the Annual USDA NIFA Animal Reproduction Project Director Meeting, San Juan, Puerto Rico, June 17, 2015. 2. Poster presentation, Liu, G.E. "Studying DNA methylation in animal reproduction and development" at the SSR 48th Annual Meeting, San Juan, Puerto Rico, June 18-22, 2015. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We prepared DNA and sequencing libraries for 20 representative dairy cattle with extreme sire conception rates, as well as proper controls for the aging effects. We generated 20 sperm DNA methylomes using the bisulfite sequencing method (MethylC-seq). We are in the process of data analysis.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2013
Citation:
Liu, G.E. 2013. An atlas of DNA methylation in diverse bovine tissues. Meeting Abstract. The Clinical Epigenome Conference Program Guide. p.17.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2015
Citation:
Liu, G.E. 2015. Studying DNA methylation in animal reproduction and development. The SSR 48th Annual Meeting Abstract. p. 289.
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Progress 09/01/13 to 08/31/14
Outputs
Target Audience: Farmers, scientists, livestock industries and policy planners who need improve animal health and production based on genome-enabled animal selection. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? Teach and mentor 1 postdoc and 2 technicians. 1. Lingyang Xu, Postdoc, contributed to DNA methylation call algorithms 2. Alexander Dimtchev,technician, contributed to PCR validation of DNA methylation results 3. Reuben Anderson,technician, contributed to PCR validation of DNA methylation results How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? We will generate over 20 representative sperm DNA methylomes of cattle with high or low male fertility traits using the bisulfite sequencing method MethylC-seq.
Impacts
What was accomplished under these goals?
Due to the government shutdown and an awarding error, we did not receive the fund unitl June 2014. We recently restarted the project by finalizing the seletion of the bull semen samples.
Publications
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