Some Things Just Have to Be Done In Vivo

Williams, Kevin Jon

doi:10.1161/atvbaha.109.187823

Cited by 8 publications

(5 citation statements)

References 48 publications

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“…A multiple traits instead of single trait analysis may be a promising way to take correlations among these traits into consideration. Multivariate analyses have been widely adopted in linkage studies [59], [60], [61], [62], [63], and it has been generally accepted that multivariate analyses outperform univariate analyses in terms of increasing statistical power and precision of parameter estimation [64], [65]. In the next step, an optimal multiple traits analytical strategy will be pursued to further enhance our GWA studies.…”

Section: Discussionmentioning

confidence: 99%

Genome Wide Association Studies for Milk Production Traits in Chinese Holstein Population

et al. 2010

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Genome-wide association studies (GWAS) based on high throughput SNP genotyping technologies open a broad avenue for exploring genes associated with milk production traits in dairy cattle. Motivated by pinpointing novel quantitative trait nucleotide (QTN) across Bos Taurus genome, the present study is to perform GWAS to identify genes affecting milk production traits using current state-of-the-art SNP genotyping technology, i.e., the Illumina BovineSNP50 BeadChip. In the analyses, the five most commonly evaluated milk production traits are involved, including milk yield (MY), milk fat yield (FY), milk protein yield (PY), milk fat percentage (FP) and milk protein percentage (PP). Estimated breeding values (EBVs) of 2,093 daughters from 14 paternal half-sib families are considered as phenotypes within the framework of a daughter design. Association tests between each trait and the 54K SNPs are achieved via two different analysis approaches, a paternal transmission disequilibrium test (TDT)-based approach (L1-TDT) and a mixed model based regression analysis (MMRA). In total, 105 SNPs were detected to be significantly associated genome-wise with one or multiple milk production traits. Of the 105 SNPs, 38 were commonly detected by both methods, while four and 63 were solely detected by L1-TDT and MMRA, respectively. The majority (86 out of 105) of the significant SNPs is located within the reported QTL regions and some are within or close to the reported candidate genes. In particular, two SNPs, ARS-BFGL-NGS-4939 and BFGL-NGS-118998, are located close to the DGAT1 gene (160bp apart) and within the GHR gene, respectively. Our findings herein not only provide confirmatory evidences for previously findings, but also explore a suite of novel SNPs associated with milk production traits, and thus form a solid basis for eventually unraveling the causal mutations for milk production traits in dairy cattle.

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Section: Discussionmentioning

confidence: 99%

Genome Wide Association Studies for Milk Production Traits in Chinese Holstein Population

et al. 2010

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“…[58] In contrast, postheparin LPL activity and mass in the GPIHBP1-Q115P proband was low, which may suggest that GPIHBP1 may be involved in the translocation of LPL to the endothelial cell surface in humans. [9,24] Interestingly, it has been proposed that GPIHBP1 may act as a stabilizer of the LPL protein and protects the LPL protein against de-activation by ANGPTL4 which is a known inhibitor of LPL activity. [19,21] Indeed, GPIHBP1-stabilized LPL is protected against deactivation by ANGPTL4.…”

Section: Gpihbp1 a Novel Protein Involved In Triglyceride Lipolysismentioning

confidence: 99%

“…LPL will then be transcytosed through the endothelial cell to reach the cell surface at the luminal site where GPIHBP1 is present, probably in lipid rafts together with syndecan1 and fatty acid transporters such as CD36. [6,9] The generated remnant particle can then go to the liver. The fatty acids will be locally internalized by CD36.…”

Section: Figurementioning

confidence: 99%

The metabolism of triglyceride-rich lipoproteins revisited: New players, new insight

et al. 2010

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Peripheral lipoprotein lipase (LPL)-mediated lipolysis of triglycerides is the first step in chylomicron/VLDL clearance involving heparan sulfate proteoglycans (HSPGs) displayed at the cell surface of the capillaries in adipose tissue, heart and skeletal muscle. The newly generated chylomicron remnant particles are then cleared by the liver, whereas VLDL remnant particles are either further modified, through the action of hepatic lipase (HL) and cholesteryl ester transfer protein (CETP), into LDL particles or alternatively directly cleared by the liver. Two proteins, lipase maturation factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), have been recently identified and have revised our current understanding of LPL maturation and LPL-mediated lipolysis. Moreover, new insights have been gained with respect to hepatic remnant clearance using genetically modified mice targeting the sulfation of HSPGs and even deletion of the most abundant heparan sulfate proteoglycan: syndecan-1. In this review, we will provide an overview of novel data on both peripheral TG hydrolysis and hepatic remnant clearance that will improve our knowledge of plasma triglyceride metabolism.

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“…We demonstrated that following the over-expression or silencing of GPIHBP1 , the mRNA expression of all of these genes was either increased or decreased. The GPIHBP1 protein localizes to the membrane of epithelial cells, where it can bind with LPL and chylomicrons, providing a platform for the lipolysis of triglyceride in chylomicrons by LPL 17 – 20 . The released non-esterified fatty acids (NEFAs) will be transported into cells by CD36 and VLDLR and used as substrates of ACACA and FASN, both of which are important enzymes in fatty acid synthesis 17 , 21 – 23 .…”

Section: Discussionmentioning

confidence: 99%

“…The GPIHBP1 protein localizes to the membrane of epithelial cells, where it can bind with LPL and chylomicrons, providing a platform for the lipolysis of triglyceride in chylomicrons by LPL 17 – 20 . The released non-esterified fatty acids (NEFAs) will be transported into cells by CD36 and VLDLR and used as substrates of ACACA and FASN, both of which are important enzymes in fatty acid synthesis 17 , 21 – 23 . When the expression of GPIHBP1 is decreased, the binding of LPL with GPIHBP1 is also decreased, such that the process of triglyceride lipolysis in mammary epithelial cells is inhibited, leading to increased accumulation of triglycerides and, thus, a higher milk fat content.…”

Section: Discussionmentioning

confidence: 99%

Functional validation of GPIHBP1 and identification of a functional mutation in GPIHBP1 for milk fat traits in dairy cattle

Yang

Wang

et al. 2017

Sci Rep

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In a previous genome-wide association study (GWAS) on milk production traits in a Chinese Holstein population, we revealed that GPIHBP1 is a novel promising candidate gene for milk fat content traits. In this study, we performed over-expression and RNAi experiments on GPIHBP1 in bovine primary mammary epithelial cells. The results showed that the expression of several important milk fat-related genes (LPL, CD36, VLDLR, ACACA and FASN) increased or decreased when the expression of GPIHBP1 was up- or down-regulated. To identify the potential functional SNP involved, we explored the genetic variants of GPIHBP1 and found that a G/A mutation (chr14:2553998) in the promoter region of GPIHBP1 significantly reduced promoter activity and had an effect on transcription factor binding sites. This finding was consistent with the lower expression of GPIHBP1 observed in the mammary gland tissue of cows harboring the homozygous AA mutation compared with wild-type homozygous GG or heterozygous AG. Furthermore, association analysis showed that cows with the AA genotype outperformed those with the GG and AG genotypes in terms of the milk fat percentage. Our study demonstrates that GPIHBP1 could be a strong candidate gene for milk fat content traits and, in particular, the G to A mutation at chr14:2553998 within GPIHBP1 could be a functional mutation related to its effects.

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Some Things Just Have to Be Done In Vivo

Cited by 8 publications

References 48 publications

Genome Wide Association Studies for Milk Production Traits in Chinese Holstein Population

Genome Wide Association Studies for Milk Production Traits in Chinese Holstein Population

The metabolism of triglyceride-rich lipoproteins revisited: New players, new insight

Functional validation of GPIHBP1 and identification of a functional mutation in GPIHBP1 for milk fat traits in dairy cattle

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