title: Evaluating intra- and inter-individual variation in the human placental transcriptome.
abstract: BACKGROUND
  Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta.
  
  
  RESULTS
  We estimate that on average, 33.2%, 58.9%, and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals, and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they each account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling, and metabolism. Many biological traits demonstrate correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection, directional selection, or diversifying selection.
  
  
  CONCLUSIONS
  We apportion placental gene expression variation into individual, population, and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.
authors.affiliation: Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany. hughes.evoanth@gmail.com.|CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, P.R. China. hughes.evoanth@gmail.com.|Current address: Institute of Evolutionary Biology (Universitat Pompeu Fabra - CSIC), PRBB, Barcelona, Catalonia, 08003, Spain. hughes.evoanth@gmail.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Hughes
authors.affiliation: Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany. mkircher@u.washington.edu.|Current address: Department of Genome Sciences, University of Washington, Seattle, Washington, USA. mkircher@u.washington.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Kircher
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, P.R. China. hezhisong@picb.ac.cn.
authors.forename: Zhisong
authors.initials: Z
authors.lastname: He
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, P.R. China. song@picb.ac.cn.
authors.forename: Song
authors.initials: S
authors.lastname: Guo
authors.affiliation: Obstetrics and Gynecology of Atlanta, 1100 Johnson Ferry Rd NE Suite 800, Center 2, Atlanta, GA, 30342, USA. gfairbrother@comcast.net.
authors.forename: Genevieve L
authors.initials: GL
authors.lastname: Fairbrother
authors.affiliation: Department of Pathology and Laboratory Medicine and Department of Biomedical Informatics, Emory University, Atlanta, GA, 30322, USA. cmoreno@emory.edu.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, 320 Yue Yang Road, Shanghai, 200031, P.R. China. khaitovich@eva.mpg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.affiliation: Max-Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, Leipzig, 04103, Germany. stoneking@eva.mpg.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Stoneking
mesh_terms: D002874:Chromosome Mapping; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D040641:Quantitative Trait Loci / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*