28 research outputs found

    Genomic Variation and Its Impact on Gene Expression in Drosophila melanogaster

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    Understanding the relationship between genetic and phenotypic variation is one of the great outstanding challenges in biology. To meet this challenge, comprehensive genomic variation maps of human as well as of model organism populations are required. Here, we present a nucleotide resolution catalog of single-nucleotide, multi-nucleotide, and structural variants in 39 Drosophila melanogaster Genetic Reference Panel inbred lines. Using an integrative, local assembly-based approach for variant discovery, we identify more than 3.6 million distinct variants, among which were more than 800,000 unique insertions, deletions (indels), and complex variants (1 to 6,000 bp). While the SNP density is higher near other variants, we find that variants themselves are not mutagenic, nor are regions with high variant density particularly mutation-prone. Rather, our data suggest that the elevated SNP density around variants is mainly due to population-level processes. We also provide insights into the regulatory architecture of gene expression variation in adult flies by mapping cis-expression quantitative trait loci (cis-eQTLs) for more than 2,000 genes. Indels comprise around 10% of all cis-eQTLs and show larger effects than SNP cis-eQTLs. In addition, we identified two-fold more gene associations in males as compared to females and found that most cis-eQTLs are sex-specific, revealing a partial decoupling of the genomic architecture between the sexes as well as the importance of genetic factors in mediating sex-biased gene expression. Finally, we performed RNA-seq-based allelic expression imbalance analyses in the offspring of crosses between sequenced lines, which revealed that the majority of strong cis-eQTLs can be validated in heterozygous individuals

    Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like experiences

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    Background The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life. Aims We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. Method Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population. Results Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (β = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (β = 0.27, s.e. = 0.10, P = 0.004). Conclusions Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse

    Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like experiences

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    Background The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life. Aims We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. Method Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population. Results Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (β = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (β = 0.27, s.e. = 0.10, P = 0.004). Conclusions Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse

    Galileo's surveying potential E5 pseudorange precision

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    New Galileo signals have great potential for pseudorange-based surveying and mapping in both optimal open-sky conditions and suboptimal under-canopy environments. This article reviews the main features of Galileo's E5 AItBO( and El (BOC signals, describes generation of realistic E5 and El pseudoranges with and without multipath sources, and presents anticipated horizontal positioning accuracy results, ranging from 4 centimeters (open-sky) to 14 centimeters (under-canopy) for E5/El
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