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Sci Rep. 2015 Oct 16;5:13950. doi: 10.1038/srep13950.

DNA methylation Landscape of body size variation in sheep.

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National Center for Molecular Genetics and Breeding of Animal, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China.
Department of Human Nutrition, Food, and Exercise, Virginia Polytechnic Institute, Blacksburg, Virginia 24061, United States.
BGI-Shenzhen, Shenzhen, Guangdong 518083, China.
Department of Human Evolutionary Biology, Harvard University, Cambridge 02138, United States.
National Center of Preservation &Utilization of Genetic Resources of Animal, Beijing 100194, China.


Sub-populations of Chinese Mongolian sheep exhibit significant variance in body mass. In the present study, we sequenced the whole genome DNA methylation in these breeds to detect whether DNA methylation plays a role in determining the body mass of sheep by Methylated DNA immunoprecipitation - sequencing method. A high quality methylation map of Chinese Mongolian sheep was obtained in this study. We identified 399 different methylated regions located in 93 human orthologs, which were previously reported as body size related genes in human genome-wide association studies. We tested three regions in LTBP1, and DNA methylation of two CpG sites showed significant correlation with its RNA expression. Additionally, a particular set of differentially methylated windows enriched in the "development process" (GO: 0032502) was identified as potential candidates for association with body mass variation. Next, we validated small part of these windows in 5 genes; DNA methylation of SMAD1, TSC1 and AKT1 showed significant difference across breeds, and six CpG were significantly correlated with RNA expression. Interestingly, two CpG sites showed significant correlation with TSC1 protein expression. This study provides a thorough understanding of body size variation in sheep from an epigenetic perspective.

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