title: A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits.
abstract: BACKGROUND
  The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed.
  
  
  RESULTS
  We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process "cellular lipid metabolism" in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number.
  
  
  CONCLUSIONS
  Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection.
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. jun.zhu@mssm.edu.|Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. jun.zhu@mssm.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. chcy75@hotmail.com.
authors.forename: Congying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. ybb_wx@hotmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. gyuanmei@hotmail.com.
authors.forename: Yuanmei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. aihsh@hotmail.com.
authors.forename: Huashui
authors.initials: H
authors.lastname: Ai
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. renjunjxau@hotmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: BGI, Shenzhen, Guangdong, China. pengbgi@gmail.com.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. zhidong.tu@mssm.edu.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Integrative Biology and Physiology, University of California at Los Angeles, Los Angeles, CA, USA. xyang123@ucla.edu.
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Integrative Biology and Physiology, University of California at Los Angeles, Los Angeles, CA, USA. qingyingmeng@ucla.edu.
authors.forename: Qingying
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Sage Bionetworks, Seattle, WA, USA. friend@sagebase.org.
authors.forename: Stephen
authors.initials: S
authors.lastname: Friend
authors.affiliation: Jiangxi Agricultural University, Nanchang, Jiangxi, China. Lushenghuang@hotmail.com.
authors.forename: Lusheng
authors.initials: L
authors.lastname: Huang
mesh_terms: D000740:Anemia / Q000235:genetics / Q000473:pathology; D000818:Animals; D001827:Body Height / Q000235:genetics; D002874:Chromosome Mapping; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D013552:Swine; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C462952:DAB2IP protein, human; D053782:Transforming Growth Factor beta3; D020703:ras GTPase-Activating Proteins