A marker-derived gene network reveals the regulatory role of PPARGC1A, HNF4G, and FOXP3 in intramuscular fat deposition of beef cattle.
High intramuscular fat (IMF) awards price premiums to beef producers and is associated with meat quality and flavor. Studying gene interactions and pathways that affect IMF might unveil causative physiological mechanisms and inform genomic selection, leading to increased accuracy of predictions of breeding value. To study gene interactions and pathways, a gene network was derived from genetic markers associated with direct measures of IMF, other fat phenotypes, feedlot performance, and a number of meat quality traits relating to body conformation, development, and metabolism that might be plausibly expected to interact with IMF biology. Marker associations were inferred from genomewide association studies (GWAS) based on high density genotypes and 29 traits measured on 10,181 beef cattle animals from 3 breed types. For the network inference, SNP pairs were assessed according to the strength of the correlation between their additive association effects across the 29 traits. The co-association inferred network was formed by 2,434 genes connected by 28,283 edges. Topological network parameters suggested a highly cohesive network, in which the genes are strongly functionally interconnected. Pathway and network analyses pointed towards a trio of transcription factors (TF) as key regulators of carcass IMF: PPARGC1A, HNF4G, and FOXP3. Importantly, none of these genes would have been deemed as significantly associated with IMF from the GWAS. Instead, a total of 313 network genes show significant co-association with the 3 TF. These genes belong to a wide variety of biological functions, canonical pathways, and genetic networks linked to IMF-related phenotypes. In summary, our GWAS and network predictions are supported by the current literature and suggest a cooperative role for the 3 TF and other interacting genes including CAPN6, STC2, MAP2K4, EYA1, COPS5, XKR4, NR2E1, TOX, ATF1, ASPH, TGS1, and TTPA as modulators of carcass and meat quality traits in beef cattle.
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia Departament de Ciencia Animal i dels Aliments, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain INRA, UMR1313 Génétique Animale et Biologie Intégrative (GABI), Domaine de Vilvert, Bâtiment GABI-320, 78352 Jouy-en-Josas, France.
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Ramayo-Caldas
The University of Queensland, Queensland Alliance for Agriculture and Food Innovation, Center for Animal Science, QLD 4062, Australia.
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Fortes
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia.
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Hudson
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia.
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Porto-Neto
Victorian Department of Environment and Primary Industries, Bundoora, VIC 3083, Australia.
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Bolormaa
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia.
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Barendse
The University of Queensland, Queensland Alliance for Agriculture and Food Innovation, Center for Animal Science, QLD 4062, Australia.
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Kelly
The University of Queensland, Queensland Alliance for Agriculture and Food Innovation, Center for Animal Science, QLD 4062, Australia.
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Moore
Victorian Department of Environment and Primary Industries, Bundoora, VIC 3083, Australia School of Land and Environment, University of Melbourne, Parkville, VIC 3010, Australia.
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Goddard
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia.
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Lehnert
CSIRO Food Futures Flagship and CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Brisbane, QLD 4067, Australia tony.reverter-gomez@csiro.au.
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Reverter
D050154:Adiposity / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002417:Cattle / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D053263:Gene Regulatory Networks / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D055106:Genome-Wide Association Study / Q000662:veterinary; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000502:physiology; D008460:Meat / Q000592:standards; D018482:Muscle, Skeletal / Q000502:physiology*; D019655:Quantitative Trait, Heritable; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D051557:Hepatocyte Nuclear Factor 4; D014157:Transcription Factors
association weight matrix; beef quality; fat deposition; genomewide association study; marbling