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Distinct genes and pathways associated with transcriptome differences in early cardiac development between fast- and slow-growing broilers.

ABSTRACT: Modern fast-growing broilers are susceptible to cardiac dysfunctions because their relatively small hearts cannot adequately meet the increased need of pumping blood through a large body mass. To improve cardiac health in broilers through breeding, we need to identify the genes and pathways that contribute to imbalanced cardiac development and occurrence of heart dysfunction. Two broiler lines-Ross 708 and Illinois-were included in this study as models of modern fast-growing and heritage slow-growing broilers, respectively. The left ventricular transcriptome were compared between the two broiler lines at day 6 and 21 post hatch through RNA-seq analysis to identify genes and pathways regulating compromised cardiac development in modern broilers. Number of differentially expressed genes (DEGs, p<0.05) between the two broiler lines increased from 321 at day 6 to 819 at day 21. As the birds grew, Ross broilers showed more DEGs (n = 1879) than Illinois broilers (n = 1117). Both broilers showed significant change of muscle related genes and immune genes, but Ross broilers showed remarkable change of expression of several lipid transporter genes including APOA4, APOB, APOH, FABP4 and RBP7. Ingenuity pathway analysis (IPA) suggested that increased cell apoptosis and inhibited cell cycle due to increased lipid accumulation, oxidative stress and endoplasmic reticulum stress may be related to the increased cardiac dysfunctions in fast-growing broilers. Cell cycle regulatory pathways like "Mitotic Roles of Polo-like Kinases" are ranked as the top changed pathways related to the cell apoptosis. These findings provide further insight into the cardiac dysfunction in modern broilers and also potential targets for improvement of their cardiac health through breeding.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6281182 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Distinct genes and pathways associated with transcriptome differences in early cardiac development between fast- and slow-growing broilers.

Zhang Jibin J Schmidt Carl J CJ Lamont Susan J SJ

PloS one 20181205 12

Modern fast-growing broilers are susceptible to cardiac dysfunctions because their relatively small hearts cannot adequately meet the increased need of pumping blood through a large body mass. To improve cardiac health in broilers through breeding, we need to identify the genes and pathways that contribute to imbalanced cardiac development and occurrence of heart dysfunction. Two broiler lines-Ross 708 and Illinois-were included in this study as models of modern fast-growing and heritage slow-gr ...[more]

PMID: 30517173

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Project description:IntroductionGrowth traits are important in poultry production, however, little is known for its regulatory mechanism at epigenetic level. Therefore, in this study, we aim to compare DNA methylation profiles between fast- and slow-growing broilers in order to identify candidate genes for chicken growth. Methylated DNA immunoprecipitation-sequencing (MeDIP-seq) was used to investigate the genome-wide DNA methylation pattern in high and low tails of Recessive White Rock (WRR(h); WRR(l)) and that of Xinhua Chickens (XH(h); XH(l)) at 7 weeks of age. The results showed that the average methylation density was the lowest in CGIs followed by promoters. Within the gene body, the methylation density of introns was higher than that of UTRs and exons. Moreover, different methylation levels were observed in different repeat types with the highest in LINE/CR1. Methylated CGIs were prominently distributed in the intergenic regions and were enriched in the size ranging 200-300 bp. In total 13,294 methylated genes were found in four samples, including 4,085 differentially methylated genes of WRR(h) Vs. WRR(l), 5,599 of XH(h) Vs. XH(l), 4,204 of WRR(h) Vs. XH(h), as well as 7,301 of WRR(l) Vs. XH(l). Moreover, 132 differentially methylated genes related to growth and metabolism were observed in both inner contrasts (WRR(h) Vs. WRR(l) and XH(h) Vs. XH(l)), whereas 129 differentially methylated genes related to growth and metabolism were found in both across-breed contrasts (WRR(h) Vs. XH(h) and WRR(l) Vs. XH(l)). Further analysis showed that overall 75 genes exhibited altered DNA methylation in all four contrasts, which included some well-known growth factors of IGF1R, FGF12, FGF14, FGF18, FGFR2, and FGFR3. In addition, we validate the MeDIP-seq results by bisulfite sequencing in some regions.ConclusionsThis study revealed the global DNA methylation pattern of chicken muscle, and identified candidate genes that potentially regulate muscle development at 7 weeks of age at methylation level.

Project description:BackgroundModern fast-growing broilers are susceptible to heart failure under heat stress because their relatively small hearts cannot meet increased need of blood pumping. To improve the cardiac tolerance to heat stress in modern broilers through breeding, we need to find the important genes and pathways that contribute to imbalanced cardiac development and frequent occurrence of heat-related heart dysfunction. Two broiler lines - Ross 708 and Illinois - were included in this study as a fast-growing model and a slow-growing model respectively. Each broiler line was separated to two groups at 21 days posthatch. One group was subjected to heat stress treatment in the range of 35-37 °C for 8 h per day, and the other was kept in thermoneutral condition. Body and heart weights were measured at 42 days posthatch, and gene expression in left ventricles were compared between treatments and broiler lines through RNA-seq analysis.ResultsBody weight and normalized heart weight were significantly reduced by heat stress only in Ross broilers. RNA-seq results of 44 genes were validated using Biomark assay. A total of 325 differentially expressed (DE) genes were detected between heat stress and thermoneutral in Ross 708 birds, but only 3 in Illinois broilers. Ingenuity pathway analysis (IPA) predicted dramatic changes in multiple cellular activities especially downregulation of cell cycle. Comparison between two lines showed that cell cycle activity is higher in Ross than Illinois in thermoneutral condition but is decreased under heat stress. Among the significant pathways (P < 0.01) listed for different comparisons, "Mitotic Roles of Polo-like Kinases" is always ranked first.ConclusionsThe increased susceptibility of modern broilers to cardiac dysfunction under heat stress compared to slow-growing broilers could be due to diminished heart capacity related to reduction in relative heart size. The smaller relative heart size in Ross heat stress group than in Ross thermoneutral group is suggested by the transcriptome analysis to be caused by decreased cell cycle activity and increased apoptosis. The DE genes in RNA-seq analysis and significant pathways in IPA provides potential targets for breeding of heat-tolerant broilers with optimized heart function.

Project description:Chicken growth traits are important in poultry production, however, little is known for its regulatory mechanism at epigenetic level. Therefore, this study aims to compare DNA methylation profiles between fast- and slow-growing broilers in order to identify candidate genes underlying chicken growth. Methylated DNA immunoprecipitation-sequencing (MeDIP-seq) was used to investigate the genome-wide DNA methylation pattern in high and low tails of Recessive White Rock (WRRh, WRRl) and that of Xinhua Chickens (XHh, XHl). The results showed that the average of methylation density was the lowest in CGIs followed by promoters. Within the gene body, the methylation density of introns was higher than UTRs and exons. Moreover, different methylation levels were observed in different repeat types with the highest in LINE/CR1. Methylated CGIs were prominently distributed in the intergenic regions and were enriched in the size range of 200-300 bp. In total 13,294 methylated genes were found in four samples, including 4,085 differentially methylated genes between WRRh and WRRl, 5,599 between XHh and XHl, 4,204 between WRRh and XHh, as well as 7,301 between WRRl and XHl. Moreover, 132 differentially methylated genes related to growth and metabolism were observed in both inner contrasts (WRRh Vs. WRRl and XHh Vs. XHl), whereas 129 differentially methylated genes related to growth and metabolism were found in both across-breed contrasts (WRRh Vs. XHh and WRRl Vs. XHl). Further analysis showed that overall 75 genes exhibited altered DNA methylation in all four contrasts, which included some well-known growth factors of IGF1R, FGF12, FGF14, FGF18, FGFR2, and FGFR3. In addition, we further validate the MeDIP-seq results by bisulfite sequencing in some regions. 12 Breast muscle samples were collected from two breeds of different growth rate, Recessive White Rock (WRR) and Xinhua Chickens (XH). Each breed included low and high-weight groups and 3 samples from each group were pooled equally for methylated DNA immunoprecipitation-sequencing (MeDIP-seq).

Project description:Circannual rhythms in vertebrates can influence a wide variety of physiological processes. Some notable examples include annual reproductive cycles and for poikilotherms, seasonal changes modulating growth. Increasing water temperature elevates growth rates in fishes, but increases in photoperiod regime can have similar influences even at constant temperature. Therefore, in order to understand the dynamics of growth in fish it is important to consider the background influence of photoperiod regime on gene expression differences. This study examined the influence of a declining photoperiod regime (winter solstice) compared to an increasing photoperiod regime (spring equinox) on white muscle transcriptome profiles in fast and slow-growing rainbow trout from a commercial aquaculture strain.Slow-growing fish could be characterized as possessing transcriptome profiles that conform in many respects to an endurance training regime in humans. They have elevated mitochondrial and cytosolic creatine kinase expression levels and appear to suppress mTOR-signaling as evidenced by elevated TSC2 expression, and they also have elevated p53 levels. Large fish display a physiological repertoire that may be consistent with strength/resistance physiology having elevated cytoskeletal gene component expression and glycogen metabolism cycling along with higher PI3K levels. In many respects small vs. large fish match eccentric vs. concentric muscle expression patterns, respectively. Lipid metabolic genes are also more elevated in larger fish, the most notable being the G0S2 switch gene. M and Z-line sarcomere remodelling appears to be more prevalent in large fish. Twenty-three out of 26 gene families with previously reported significant SNP-based growth differences were detected as having significant expression differences.Larger fish display a broader array of genes showing higher expression, and their profiles are more similar to those observed in December lot fish (i.e., an accelerated growth period). Conversely, small fish display gene profiles more similar to seasonal growth decline phases (i.e., September lot fish). Overall, seasonal timing was coupled to greater differences in gene expression compared to differences associated with fish size.

Dataset Information

Distinct genes and pathways associated with transcriptome differences in early cardiac development between fast- and slow-growing broilers.

Publications

Distinct genes and pathways associated with transcriptome differences in early cardiac development between fast- and slow-growing broilers.

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