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      Exploring Genomic Variants Related to Residual Feed Intake in Local and Commercial Chickens by Whole Genomic Resequencing

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          Abstract

          Improving feed efficiency is a major goal in poultry production to reduce production costs and increase profitability. The genomic variants and possible molecular mechanisms responsible for residual feed intake (RFI) in chickens, however, remain poorly understood. In this study, using both local and commercial breeds, genome re-sequencing of low RFI and high RFI chickens was performed to elucidate the genomic variants underlying RFI. Results showed that 8,505,214 and 8,479,041 single nucleotide polymorphisms (SNPs) were detected in low and high RFI Beijing-You chickens, respectively; 8,352,008 and 8,372,769 SNPs were detected in low- and high-RFI Cobb chickens, respectively. Through a series of filtering processes, 3746 candidate SNPs assigned to 1137 genes in Beijing-You chickens and 575 candidate SNPs (448 genes) in Cobb chickens were found. The validation of the selected 191 SNPs showed that 46 SNPs were significantly associated with the RFI in an independent population of 779 Cobb chickens, suggesting that the method of screening associated SNPs with whole genome sequencing (WGS) strategy was reasonable. Functions annotation of RFI-related genes indicated that genes in Beijing-You were enriched in lipid and carbohydrate metabolism, as well as the phosphatase and tensin homolog (PTEN) signaling pathway. In Cobb, however, RFI-related genes were enriched in the feed behavior process and cAMP responsive element binding protein (CREB) signaling pathway. For both breeds, organismal development physiological processes were enriched. Correspondingly, NOS1, PHKG1, NEU3 and PIP5K1B were differentially expressed in Beijing-You, while CDC42, CSK, PIK3R3, CAMK4 and PLCB4 were differentially expressed in Cobb, suggesting that these might be key genes that contribute to RFI. The results of the present study identified numerous novel SNPs for RFI, which provide candidate biomarkers for use in the genetic selection for RFI. The study has improved knowledge of the genomic variants and potential biological pathways underlying RFI in chickens.

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          Most cited references29

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          R: language and environment for statistical computing

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            Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism.

            Hepatic insulin resistance affects both carbohydrate and lipid metabolism. It has been proposed that insulin controls these 2 metabolic branches through distinct signaling pathways. FoxO transcription factors are considered effectors of the pathway regulating hepatic glucose production. Here we show that adenoviral delivery of constitutively nuclear forkhead box O1 (FoxO1) to mouse liver results in steatosis arising from increased triglyceride accumulation and decreased fatty acid oxidation. FoxO1 gain of function paradoxically increased insulin sensitivity by promoting Akt phosphorylation, while FoxO1 inhibition via siRNA decreased it. We show that FoxO1 regulation of Akt phosphorylation does not require DNA binding and is associated with repression of the pseudokinase tribble 3 (Trb3), a modulator of Akt activity. This unexpected dual role of FoxO1 in promoting insulin sensitivity and lipid synthesis in addition to glucose production has the potential to explain the peculiar admixture of insulin resistance and sensitivity that is commonly observed in the metabolic syndrome.
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              Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

              Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets. Our association analysis revealed a uniform pattern of Warburg effect mutations influencing prognosis across all tumor types, while copy number alterations in the electron transport chain gene SCO2, fatty acid uptake (CAV1, CD36) and lipogenesis (PPARA, PPARD, MLXIPL) genes were enriched in metastatic tumors. Using gene expression profiles, we established a gene-signature (CAV1, CD36, MLXIPL, CPT1C, CYP2E1) that strongly associated with epithelial-mesenchymal program across multiple cancers. Moreover, stratification of samples based on the copy number or expression profiles of the genes identified in our analysis revealed a significant effect on patient survival rates, thus confirming prominent roles of fatty acid uptake and metabolism in metastatic progression and poor prognosis of human cancers.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                24 January 2018
                February 2018
                : 9
                : 2
                : 57
                Affiliations
                [1 ]Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China; liujie84130@ 123456163.com (J.L.); liuranran@ 123456caas.cn (R.L.); wangjie4007@ 123456126.com (J.W.); yhzhang1981@ 123456163.com (Y.Z.); xingsiyuan@ 123456caas.cn (S.X.); zhengmaiqing@ 123456caas.cn (M.Z.); cuihuanxian@ 123456caas.cn (H.C.); liqinghe@ 123456caas.cn (Q.L.); lipengnd@ 123456126.com (P.L.); cxyan813@ 123456163.com (X.C.); liweirfi@ 123456126.com (W.L.)
                [2 ]State Key Laboratory of Animal Nutrition, Beijing 100193, China
                [3 ]College of Animal Science, Jilin University, Changchun 130062, China
                Author notes
                [* ]Correspondence: zhaoguiping@ 123456caas.cn (G.Z.); Wenjie@ 123456caas.cn (J.W.); Tel.: +86-10-6281-5894 (J.W.); Fax: +86-010-6281-6018 (J.W.)
                [†]

                These authors contributed equally to this work.

                Article
                genes-09-00057
                10.3390/genes9020057
                5852553
                29364149
                df38d053-8542-4390-83ec-1c2214ebfac8
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 October 2017
                : 02 January 2018
                Categories
                Article

                genome resequencing,residual feed intake,genomic variants,biomarkers,chickens

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