Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

Comparative analysis of the transcriptome across distant species

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease

I. The biosynthesis of open chain terpenes in plants. II. Fractionation of the stable carbon isotopes in plants

I: Open chain terpene synthesis in plants was studied by measurement of the incorporation of potential intermediates into the rubber of the rubber producing plants Taraxacum kok saghyz and Hevea brasiliensis. Intact plants incorporate 1-C14-acetate and 2-C14-acetate into rubber without randomization of the label. [Beta]-Methylcrotonic acid was found to be an ineffective rubber precursor in intact plants. Enzymatic experiments were performed using Hevea latex as a source of enzyme. C14-acetate is rapidly incorporated into a volatile, non-acidic, non-polar substance in this system under anaerobic conditions. C14-acetate is not incorporated into rubber. Mevalonic acid is rapidly incorporated into rubber in this system. Partial degradation of the rubber indicates that no randomization occurs during incorporation. This result suggests that mevalonic acid is on the pathway of terpene synthesis in plants. II: The two stable carbon isotopes, C12 and C13, occur in nature in the ratio of about ninety to one. Various workers have shown that this ratio is not fixed, but may vary by as much as 5%. Interestingly enough, this variation is not random. Carbon reservoirs such as limestone, atmospheric CO2, land plants, algae and coal all exhibit characteristic C13/C12 ratios. This section of the dissertation is concerned with the differences between the C13/C12 ratios of plants and those of the carbon sources from which such plants have grown. Both algae and terrestrial plants have smaller C13/C12 ratios than those of dissolved carbonates and atmospheric CO2 respectively. The magnitude of this fractionation was determined for tomato plants by growing the plants from seed in CO2 of known isotopic composition. Separation of the plant material into its component chemical constituents showed that only the lipid fraction differed markedly in C13/C12 ratio from that of the plant as a whole. The lipid fraction is enriched in C12 and possesses a C13/C12 ratio similar to that of petroleums derived from land plants. A similar relation was found to exist between marine algae, their lipids, and petroleums of marine origin. The CO2 evolved by plant respiration is slightly enriched in C13 as compared to the plant. This process apparently closely related to the C12 enrichment in lipid fractions. A possible mechanism for fractionation of C13 and C12 in photosynthesis is suggested. This suggestion is supported by observations of the C13/C12 ratio of CO2 dissolved in higher plants and by determination of the fractionation which occurs during fixation of CO2 by the photosynthetic carboxylation enzyme