Recombinant DNA techniques are capable of introducing genetic changes into food organisms that are more predictable than those introduced through conventional breeding techniques. This review discusses whether the consumption of DNA in approved novel foods and novel food ingredients derived from genetically modified organisms (GMOs) can be regarded as being as safe as the consumption of DNA in existing foods. It concludes that DNA from GMOs is equivalent to DNA from existing food organisms that has always been consumed with human diets. Any risks associated with the consumption of DNA will remain, irrespective of its origin, because the body handles all DNA in the same way. The breakdown of DNA during food processing and passage through the gastrointestinal tract reduces the likelihood that intact genes capable of encoding foreign proteins will be transferred to gut microflora. The review does not specifically address food safety issues arising from the consumption of viable genetically modified microorganisms but it shows that the likelihood of transfer and functional integration of DNA from ingested food by gut microflora and/or human cells is minimal. Information reviewed does not indicate any safety concerns associated with the ingestion of DNA per se from GMOs resulting from the use of currently available recombinant DNA techniques in the food chain.
dRetinoid X receptor (RXR) is a promiscuous nuclear receptor forming heterodimers with several other receptors, which activate different sets of genes. Upon agonist treatment, the occupancy of its genomic binding regions increased, but only a modest change in the number of sites was revealed by chromatin immunoprecipitation followed by sequencing, suggesting a rather static behavior. However, such genome-wide and biochemical approaches do not take into account the dynamic behavior of a transcription factor. Therefore, we characterized the nuclear dynamics of RXR during activation in single cells on the subsecond scale using live-cell imaging. By applying fluorescence recovery after photobleaching and fluorescence correlation spectroscopy (FCS), techniques with different temporal and spatial resolutions, a highly dynamic behavior could be uncovered which is best described by a two-state model (slow and fast) of receptor mobility. In the unliganded state, most RXRs belonged to the fast population, leaving ϳ15% for the slow, chromatin-bound fraction. Upon agonist treatment, this ratio increased to ϳ43% as a result of an immediate and reversible redistribution. Coactivator binding appears to be indispensable for redistribution and has a major contribution to chromatin association. A nuclear mobility map recorded by light sheet microscopy-FCS shows that the ligand-induced transition from the fast to the slow population occurs throughout the nucleus. Our results support a model in which RXR has a distinct, highly dynamic nuclear behavior and follows hit-and-run kinetics upon activation.T ranscription is an inherently dynamic process. Paradoxically, most models of transcription factor (TF) behavior assume that TFs are bound to chromatin either permanently or with a fairly long residence time upon activation (seconds to minutes). Recent advances in genomic technologies, such as chromatin immunoprecipitation followed by sequencing (ChIP-Seq), also provided support to such static models (1, 2). However, these methods lack the appropriate time resolution to provide insights into the dynamics of activated transcription factors on the time scale of seconds or shorter.Nuclear receptors (NRs) can directly bind to DNA via their highly conserved DNA-binding domain (DBD), which is near their N termini. High-affinity binding is made possible by the two zinc finger motifs. This domain recognizes the specific hormone response elements (RE) (3), which are binding sites and/or enhancers regulating transcription of target genes. A consensus RE sequence is AGGTCA (4), which acts as a half site (binds one receptor) for homo-or heterodimer binding. The hinge region of the receptor that gives a high degree of flexibility to the overall structure is located next to the DBD. This part of the protein harbors the nuclear localization signal (NLS) as well. The core of nuclear receptor action lies in the ligand-binding domain (LBD), through which dimer formation, ligand binding, coregulator binding, and trans activation occur. Retinoid X recepto...
Genomic evaluation methods today use single nucleotide polymorphism (SNP) as genomic markers to trace quantitative trait loci (QTL). Today most genomic prediction procedures use biallelic SNP markers. However, SNP can be combined into short, multiallelic haplotypes that can improve genomic prediction due to higher linkage disequilibrium between the haplotypes and the linked QTL. The aim of this study was to develop a method to identify the haplotypes, which can be expected to be superior in genomic evaluation, as compared with either SNP or other haplotypes of the same size. We first identified the SNP (termed as QTL-SNP) from the bovine 50K SNP chip that had the largest effect on the analyzed trait. It was assumed that these SNP were not the causative mutations and they merely indicated the approximate location of the QTL. Haplotypes of 3, 4, or 5 SNP were selected from short genomic windows surrounding these markers to capture the effect of the QTL. Two methods described in this paper aim at selecting the most optimal haplotype for genomic evaluation. They assumed that if an allele has a high frequency, its allele effect can be accurately predicted. These methods were tested in a classical validation study using a dairy cattle population of 2,235 bulls with genotypes from the bovine 50K SNP chip and daughter yield deviations (DYD) on 5 dairy cattle production traits. Combining the SNP into haplotypes was beneficial with all tested haplotypes, leading to an average increase of 2% in terms of correlations between DYD and genomic breeding value estimates compared with the analysis when the same SNP were used individually. Compared with haplotypes built by merging the QTL-SNP with its flanking SNP, the haplotypes selected with the proposed criteria carried less under- and over-represented alleles: the proportion of alleles with frequencies <1 or >40% decreased, on average, by 17.4 and 43.4%, respectively. The correlations between DYD and genomic breeding value estimates increased by 0.7 to 0.9 percentage points when the haplotypes were selected using any of the proposed methods compared with using the haplotypes built from the QTL-SNP and its flanking markers. We showed that the efficiency of genomic prediction could be improved at no extra costs, only by selecting the proper markers or combinations of markers for genomic prediction. One of the presented approaches was implemented in the new genomic evaluation procedure applied in dairy cattle in France in April 2015.
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