Quantitative trait loci affecting the difference in pigmentation between Drosophila yakuba and D. santomea

Using quantitative trait locus (QTL) mapping, we studied the genetic basis of the difference in pigmentation between two sister species of Drosophila: Drosophila yakuba, which, like other members of the D. melanogaster subgroup, shows heavy black pigmentation on the abdomen of males and females, and D. santomea, an endemic to the African island of S?o Tomé, which has virtually no pigmentation. Here we mapped four QTL with large effects on this interspecific difference in pigmentation: two on the X chromosome and one each on the second and third chromosomes. The same four QTL were detected in male hybrids in the backcrosses to both D. santomea and D. yakuba and in the female D. yakuba backcross hybrids. All four QTL exhibited strong epistatic interactions in male backcross hybrids, but only one pair of QTL interacted in females from the backcross to D. yabuka. All QTL from each species affected pigmentation in the same direction, consistent with adaptive evolution driven by directional natural selection. The regions delimited by the QTL included many positional candidate loci in the pigmentation pathway, including genes affecting catecholamine biosynthesis, melanization of the cuticle, and many additional pleiotropic effects.     

Effects of interleukin-8 on granulation tissue maturation

The inflammatory alpha-chemokine, interleukin-8 (IL-8), affects the function and recruitment of various inflammatory cells, fibroblasts, and keratinocytes. Gap junctions are anatomical channels that facilitate the direct passage of small molecules between cells. The hypothesis is that IL-8 enhances gap junctional intercellular communication (GJIC) between fibroblasts in granulation tissue, which increases the rate of granulation tissue maturation. In vitro, human dermal fibroblasts were incubated with IL-8 prior to scrape loading, a technique that quantifies GJIC. Polyvinyl alcohol (PVA) sponges were implanted within subcutaneous pockets in rats and received local injections of either IL-8 or saline and were harvested on day 11. In vitro, IL-8 treated fibroblasts demonstrated an increase in GJIC by scrape loading compared to saline treated controls. In vivo, IL-8 treated PVA sponges demonstrated a decrease in cell density and an increase in vascularization compared to saline controls by H&E staining. Polarized light viewed Sirius red-stained specimens demonstrated greater collagen birefringence intensity, indicating thicker, more-mature collagen fibers. IL-8 increases GJIC in cultured fibroblasts and induces a more rapid maturation of granulation tissue.     

Pedstrip: extracting a maximal subset of available,unrelated individuals from a pedigree

SUMMARY: Certain types of genetic analysis are simplified by assembling a collection of unrelated individuals, e.g. case-control experiments. If a family study is being performed then it will be necessary to extract subsets of unrelated, available individuals from pedigress. Our program provides an optimal method for performing this task. AVAILABILITY: The software is available, free of charge, on request from Oxagen Ltd. SUPPLEMENTARY INFORMATION: http://www.oxagen.co.uk     

Quantitative genetics of ovariole number in Drosophila melanogaster. II. Mutational variation and genotype-environment interaction.

The rare alleles model of mutation-selection balance (MSB) hypothesis for the maintenance of genetic variation was evaluated for two quantitative traits, ovariole number and body size. Mutational variances (VM) for these traits, estimated from mutation accumulation lines, were 4.75 and 1.97 x 10(-4) times the environmental variance (VE), respectively. The mutation accumulation lines were studied in three environments to test for genotype x environment interaction (GEI) of new mutations; significant mutational GEI was found for both traits. Mutations for ovariole number have a quadratic relationship with competitive fitness, suggesting stabilizing selection for the trait; there is no significant correlation between mutations for body size and competitive fitness. Under MSB, the ratio of segregating genetic variance, VG, to mutational variance, VM, estimates the inverse of the selection coefficient against a heterozygote for a new mutation. Estimates of VG/VM for ovariole number and body size were both approximately 1.1 x 10(4). Thus, MSB can explain the level of variation, if mutations affecting these traits are under very weak selection, which is inconsistent with the empirical observation of stabilizing selection, or if the estimate of VM is biased downward by two orders of magnitude. GEI is a possible alternative explanation.     

Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster

Reactive oxygen species (ROS) are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB). We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease.     

Genetics of alcohol consumption in Drosophila melanogaster

Individual variation in alcohol consumption in human populations is determined by genetic, environmental, social and cultural factors. In contrast to humans, genetic contributions to complex behavioral phenotypes can be readily dissected in Drosophila, where both the genetic background and environment can be controlled and behaviors quantified through simple high‐throughput assays. Here, we measured voluntary consumption of ethanol in ～3000 individuals of each sex from an advanced intercross population derived from 37 lines of the Drosophila melanogaster Genetic Reference Panel. Extreme quantitative trait loci mapping identified 385 differentially segregating allelic variants located in or near 291 genes at P < 10^?8. The effects of single nucleotide polymorphisms associated with voluntary ethanol consumption are sex‐specific, as found for other alcohol‐related phenotypes. To assess causality, we used RNA interference knockdown or P{MiET1} mutants and their corresponding controls and functionally validated 86% of candidate genes in at least one sex. We constructed a genetic network comprised of 23 genes along with a separate trio and a pair of connected genes. Gene ontology analyses showed enrichment of developmental genes, including development of the nervous system. Furthermore, a network of human orthologs showed enrichment for signal transduction processes, protein metabolism and developmental processes, including nervous system development. Our results show that the genetic architecture that underlies variation in voluntary ethanol consumption is sexually dimorphic and partially overlaps with genetic factors that control variation in feeding behavior and alcohol sensitivity. This integrative genetic architecture is rooted in evolutionarily conserved features that can be extrapolated to human genetic interaction networks.     

A high incidence of jaagsiekte following experimental cold exposures in housed sheep

The fortuitous occurrence of cases of jaagsiekte (sheep pulmonary adenomatosis) in a group of young Scottish Blackface sheep exposed to experimental cold stress is described. The incidence (11/62 cases) was high and the age of onset early (less than 20 months) by comparison with the authors' local experience of the disease. There was also some indication that males were more susceptible (9/26) than females (2/36). The results are not conclusive, but suggest the need for similar cold stress experiments in animals deliberately infected with the disease.

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Zusammenfassung Es wird über das zufällige Auftreten von Jaagsiekte (Lungenadenomatose der Schafe) in einer Gruppe von Schottisch-Blackface Schafen berichtet, die in einem Kältebelastungsversuch verwendet wurden. Die Häufigkeit war hoch (11/62 Fälle) und nach den Erfahrungen der Autoren früh, denn die Tiere waren unter 20 Monate alt. Ausserdem bestanden Hinweise auf Geschlechtsunterschiede in der Empfindlichkeit, weil mehr männliche (9/26) als weibliche Tiere (2/36) erkrankten. Die Ergebnisse sind nicht endgültig. Zur weiteren Abklärung sind Versuche erforderlich, in denen vorsätzlich infizierte Tiere der gleichen Kältebelastung ausgesetzt werden.

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Resume On rapporte ici sur l'apparition fortuite de "Jaagsiekte" (adénomatose pulmonaire du mouton) dans un groupe de moutons de la race écossaise à face noire faisant l'objet d'un essai de contrainte au froid. La fréquence des cas d'infections était élevée (11 bêtes malades sur 62) et très précoce selon l'expérience des auteurs, les animaux n'étant âgés que de 20 mois au plus. En outre, on en tire certaines indications concernant une différence possible entre les sexes, vu que la proportion des béliers atteints (9/26) est nettement plus élevée que celle des brebis malades (2/36). Ces résultats ne sont cependant pas définitifs. Afin de les compléter, il faudrait placer des animaux préalablement infectés dans des conditions semblables de contrainte au froid.