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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01032

Analysis of the progeny of sibling matings reveals regulatory variation impacting the transcriptome of immune cells in commercial chickens

Lucy Freem1,  Kim M. Summers2,  Almas Gheyas1,  Androniki Psifidi3,  Kay Boulton1, Amanda McCallum1, Jenny O'Dell1,  Stephen J. Bush4 and  David Hume5*
  • 1Roslin Institute, University of Edinburgh, United Kingdom
  • 2Translational Research Institute, University of Queensland, Australia
  • 3Department of Clinical Science and Services, The Royal Veterinary College, University of London, United Kingdom
  • 4Nuffield Department of Medicine, Medical Sciences Division, University of Oxford, United Kingdom
  • 5University of Queensland, Australia

There is increasing recognition that the underlying genetic variation contributing to complex traits influences transcriptional regulation and can be detected at a population level as expression quantitative trait loci (eQTL). At the level of an individual, allelic variation in transcriptional regulation of individual genes can be detected by measuring allele-specific expression in RNAseq data. We reasoned that extreme variants in gene expression could be identified by analysis of inbred progeny with shared grandparents. Commercial chickens have been intensively selected for production traits. Selection is associated with large blocks of linkage disequilibrium with considerable potential for co-selection of closely linked “hitch-hiker alleles” affecting traits unrelated to the feature being selected, such as immune function, with potential impact on the productivity and welfare of the animals. To test this hypothesis we sequenced a founder population of commercial broiler and layer birds. These birds clearly segregated genetically based upon breed type. Each genome contained numerous candidate null mutations, protein-coding variants predicted to be deleterious and extensive non-coding polymorphism. We mated selected broiler-layer pairs then generated cohorts of F2 birds by sibling mating of the F1 generation. Despite the predicted prevalence of deleterious coding variation in the genomic sequence of the founders clear detrimental impacts of inbreeding on survival and post-hatch development were detected in only one F2 sibship of fifteen. There was no effect on circulating leukocyte populations in hatchlings. In selected F2 sibships we performed RNAseq analysis of the spleen and isolated bone marrow-derived macrophages (with and without lipopolysaccharide stimulation). The results confirm the predicted emergence of very large differences in expression of individual genes and sets of genes. Network analysis of the results identified clusters of co-expressed genes that vary between individuals and suggested the existence of trans-acting variation in the expression of the interferon response factor (IRF) family that distinguishes the parental broiler and layer birds. This study shows that the impact of inbreeding can be substantial at the transcriptional level, and potentially opens a route to accelerate selection using specific alleles known to be associated with desirable expression levels

Keywords: chicken, Transcriptome, macrophage, allele, Genetics

Received: 03 Jul 2019; Accepted: 25 Sep 2019.

Copyright: © 2019 Freem, Summers, Gheyas, Psifidi, Boulton, McCallum, O'Dell, Bush and Hume. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. David Hume, University of Queensland, Brisbane, Australia, David.Hume@uq.edu.au