title: Genetic variability of transcript abundance in pig peri-mortem skeletal muscle: eQTL localized genes involved in stress response, cell death, muscle disorders and metabolism.
abstract: BACKGROUND
  The genetics of transcript-level variation is an exciting field that has recently given rise to many studies. Genetical genomics studies have mainly focused on cell lines, blood cells or adipose tissues, from human clinical samples or mice inbred lines. Few eQTL studies have focused on animal tissues sampled from outbred populations to reflect natural genetic variation of gene expression levels in animals. In this work, we analyzed gene expression in a whole tissue, pig skeletal muscle sampled from individuals from a half sib F2 family shortly after slaughtering.
  
  
  RESULTS
  QTL detection on transcriptome measurements was performed on a family structured population. The analysis identified 335 eQTLs affecting the expression of 272 transcripts. The ontologic annotation of these eQTLs revealed an over-representation of genes encoding proteins involved in processes that are expected to be induced during muscle development and metabolism, cell morphology, assembly and organization and also in stress response and apoptosis. A gene functional network approach was used to evidence existing biological relationships between all the genes whose expression levels are influenced by eQTLs. eQTLs localization revealed a significant clustered organization of about half the genes located on segments of chromosome 1, 2, 10, 13, 16, and 18. Finally, the combined expression and genetic approaches pointed to putative cis-drivers of gene expression programs in skeletal muscle as COQ4 (SSC1), LOC100513192 (SSC18) where both the gene transcription unit and the eQTL affecting its expression level were shown to be localized in the same genomic region. This suggests cis-causing genetic polymorphims affecting gene expression levels, with (e.g. COQ4) or without (e.g. LOC100513192) potential pleiotropic effects that affect the expression of other genes (cluster of trans-eQTLs).
  
  
  CONCLUSIONS
  Genetic analysis of transcription levels revealed dependence among molecular phenotypes as being affected by variation at the same loci. We observed the genetic variation of molecular phenotypes in a specific situation of cellular stress thus contributing to a better description of muscle physiologic response. In turn, this suggests that large amounts of genetic variation, mediated through transcriptional networks, can drive transient cell response phenotypes and contribute to organismal adaptative potential.
authors: Laboratoire de Génétique Cellulaire, INRA UMR444, Chemin de Borde Rouge, F-31326 Castanet-Tolosan, France. Laurence.Liaubet@toulouse.inra.fr
authors: Laurence
authors: L
authors: Liaubet
authors: Valérie
authors: V
authors: Lobjois
authors: Thomas
authors: T
authors: Faraut
authors: Aurélie
authors: A
authors: Tircazes
authors: Francis
authors: F
authors: Benne
authors: Nathalie
authors: N
authors: Iannuccelli
authors: José
authors: J
authors: Pires
authors: Jérome
authors: J
authors: Glénisson
authors: Annie
authors: A
authors: Robic
authors: Pascale
authors: P
authors: Le Roy
authors: Magali
authors: M
authors: Sancristobal
authors: Pierre
authors: P
authors: Cherel
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D002874:Chromosome Mapping; D016000:Cluster Analysis; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D008297:Male; D058977:Molecular Sequence Annotation; D018482:Muscle, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D040641:Quantitative Trait Loci; D013312:Stress, Physiological / Q000235:genetics; D013552:Swine / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome