A marker-derived gene network reveals the regulatory role of PPARGC1A, HNF4G, and FOXP3 in intramuscular fat deposition of beef cattle1

Abstract

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.

Genome‐wide scan for runs of homozygosity in the composite Montana Tropical® beef cattle

“…Only three genes (XKR4, MT1E, and CSMD3) were identified in both biological types and the first two are noteworthy to highlight given their role in cattle productive traits. The XKR4 (XK, Kell blood group complex subunitrelated family, member 4) gene has been associated with several economically important traits in the beef cattle such as intramuscular fat (Ramayo-Caldas et al, 2014) and subcutaneous rump fat thickness (Bolormaa et al, 2011;Porto Neto, Bunch, Harrison, & Barendse, 2012). This gene has also been described to have functions associated with serum prolactin concentrations in the Angus-Simmental-Charolais crossbred (Bastin et al, 2014), feed intake in crossbred steers (Lindholm-Perry et al, 2012), age at puberty in Brahman (Fortes et al, 2012), and backfat thickness (Silva et al, 2017), birth weight (Terakado et al, 2018) and meat tenderness (Magalhães et al, 2016) in the Nellore cattle.…”

Longitudinal muscle gene expression patterns associated with differential intramuscular fat in cattle

“…It has not yielded to genome-wide association studies -that is, there are no reliable DNA markers that explain substantial amounts of phenotypic across populations and breeds (Pannier et al, 2010). However, application of the latest thinking in network theory has been exploited to reverse engineer a plausible set of contributing regulatory molecules (PPARGC1A, HNF4G, FOXP3) based on single nucleotide polymorphism association data across three breed types, Bos taurus, Bos indicus and tropical composites (Ramayo-Caldas et al, 2014).…”

Locus‐specific ancestry to detect recent response to selection in admixed Swiss Fleckvieh cattle

“…GTPBP4 on chromosome13 is a gene responsible for morphology traits (Ramayo‐Caldas et al . ). Patterns of Rsb and Δ ancestry for the two regions on chromosomes 13 and 18 are visualized in Fig.…”