1Joint first authors.Abbreviations used: HI, H-Invitational; hNAcc, human nucleus accumbens; lncRNAs, long non-coding RNAs; MIAT, myocardial infarction associated transcript; MEG3, maternally expressed gene 3; NEAT1, nuclear enriched abundant transcript 1; NEAT2, nuclear enriched abundant transcript 2; qRT-PCR, quantitative real time-PCR. AbstractAlthough recent data suggest that some long non-coding RNAs (lncRNAs) exert widespread effects on gene expression and organelle formation, lncRNAs as a group constitute a sizable but poorly characterized fraction of the human transcriptome. We investigated whether some human lncRNA sequences were fortuitously represented on commonly used microarrays, then used this annotation to assess lncRNA expression in human brain. A computational and annotation pipeline was developed to identify lncRNA transcripts represented on Affymetrix U133 arrays. A previously published dataset derived from human nucleus accumbens was then examined for potential lncRNA expression. Twenty-three lncRNAs were determined to be represented on U133 arrays. Of these, dataset analysis revealed that five lncRNAs were consistently detected in samples of human nucleus accumbens. Strikingly, the abundance of these lncRNAs was upregulated in human heroin abusers compared to matched drug-free control subjects, a finding confirmed by quantitative PCR. This study presents a paradigm for examining existing Affymetrix datasets for the detection and potential regulation of lncRNA expression, including changes associated with human disease. The finding that all detected lncRNAs were up-regulated in heroin abusers is consonant with the proposed role of lncRNAs as mediators of widespread changes in gene expression as occur in drug abuse. In addition to sequence conservation, the precise temporal and cellular specificity of lncRNA expression is considered prima facie evidence of their functional importance. Nowhere is this more evident than in the CNS, where scores of lncRNAs exhibit robust and specific expression patterns and likely influence brain development, neurotransmission, and neuropsychiatric disorders (Mercer et al. 2008;Qureshi et al. 2010). Although our understanding in this regard is rudimentary, a recent study (Faghihi et al. 2008) found that one particular lncRNA is directly implicated in the increased CNS abundance of Ab 1-42 seen in Alzheimer's disease.In the course of our previous Affymetrix microarray studies of postmortem brain from human drug abusers (Albertson et al. 2006), we found that one of the transcripts most robustly increased by drug abuse was derived from a gene assumed to encode a hypothetical protein (LOC150271). Subsequent bioinformatic analysis has revealed that this transcript does not encode a protein but actually corresponds to a known lncRNA, myocardial infarction associated transcript (MIAT) (Ishii et al. 2006). Given the proposed role of some lncRNAs as top-down regulators of gene expression, and the widespread changes in gene expression seen in drug abuse (Albertson et al. 2...
The genomic basis of primate phenotypic uniqueness remains obscure, despite increasing genome and transcriptome sequence data availability. Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes are poorly characterized. To discover such genes genomewide, we screened a catalog of 38,037 human transcriptional units (TUs), compiled from EST and cDNA sequences in conjunction with the FANTOM3 transcriptome project. We identified 131 TUs from transcribed sequences residing within primate-specific insertions in 9-species sequence alignments and outside of segmental duplications. Exons of 120 (92%) of the TUs contained interspersed repeats, indicating that repeat insertions may have contributed to primate-specific gene genesis. Fifty-nine (46%) primate-specific TUs may encode proteins. Although primate-specific TU transcript lengths were comparable to known human gene mRNA lengths overall, 92 (70%) primate-specific TUs were single-exon. Thirty-two (24%) primate-specific TUs were localized to subtelomeric and pericentromeric regions. Forty (31%) of the TUs were nested in introns of known genes, indicating that primate-specific TUs may arise within older, protein-coding regions. Primate-specific TUs were preferentially expressed in reproductive organs and tissues ( P < 0.011), consistent with the expectation that emergence of new, lineage-specific genes may accompany speciation or reproduction. Of the 33 primate-specific TUs with human Affymetrix microarray probe support, 21 were differentially expressed in human teratozoospermia. In addition to elucidating the likely functional relevance of primate-specific TUs to reproduction, we present a set of primate-specific genes for future functional studies, and we implicate nonduplicated pericentromeric and subtelomeric regions in gene genesis.
This study examined patterns of changes in plasma fatty acids and carotenoids when women were asked to follow a novel, Greek-Mediterranean exchange list diet. A total of 69 healthy, non-obese, women ages 25–59, were randomized to either continue their own usual diet or to follow a modified Mediterranean diet for six months. There were no significant changes in blood lipids, triacylglycerol, insulin, glucose or C-reactive protein. Mean plasma carotenoids increased by 55%, which is consistent with a large increase in fruit and vegetable consumption. Likewise, changes in fat intakes were reflected in blood fatty acids, with a 25% increase in mean plasma monounsaturated fatty acids (MUFA). Principal component analysis was conducted to examine the sources of inter-individual variation for changes in carotenoid and fatty acid levels. Changes in the Mediterranean diet were clustered together in four components that accounted for 78% of the variance in plasma levels. Increases in plasma lutein, α- and β-carotene clustered together in a “vegetable” pattern, and increases in carotenoids found in fruit, β-cryptoxanthin and zeaxanthin, also clustered together but accounted for less of the variance. Increases in plasma MUFA were clustered with a decrease in plasma polyunsaturated fatty acids, consistent with substitution in the type of oils consumed. The only association of fatty acid levels with carotenoids was that of lycopene, which clustered together with an increase in saturated fatty acids. The changes in blood levels indicate the exchange list diet was effective for targeting Mediterranean nutrient intakes using foods available in the United States.
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