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Biomedical subjects

Greg Gibson

Publications and source records attributed to Greg Gibson.

9 recordsLinked to original sources
PubMed2026

Gene expression profiling identifies potential biomarkers for vaso-occlusive episodes in sickle cell disease.

Vaso-occlusive episodes (VOEs) or acute pain events, involving complex interactions between sickle erythrocytes and other blood cells, are a hallmark of sickle cell disease (SCD). In this study, we analyzed changes in peripheral blood transcriptomes between steady state and VOEs in individuals with SCD. We followed a cohort of 174 individuals with SCD with or without chronic pain and collected peripheral blood at clinic visits (steady state) and during hospitalizations (VOEs). We performed RNA-Seq profiling of CD45+ leukocytes and CD71+ erythroid cells. Pathways linked to complement activation, coagulation, and IL-6/JAK/STAT3 signaling were enriched during VOEs in the CD45+ cells. Contrastingly, the CD71+ cells showed an enrichment of pathways related to the cell cycle, such as mTORC1 signaling and the G2M checkpoint during VOEs. We then analyzed the expression changes of genes in patients with longitudinal data to determine potential biomarkers for VOEs. Expression of 4 genes - FAM20A, IL1B, MS4A4A, and SERPINB2 - was elevated during VOEs compared with steady state in the majority of patients. Furthermore, our results indicate that patients experiencing chronic pain exhibited 44% increased enrichment of significant pathways during VOEs when compared with patients without chronic pain.

Humans↗
PubMed2003

Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila.

The molecular genetics of several signal transduction pathways is well characterized, providing an opportunity to address the nature of the population genetic forces acting on functionally related suites of pleiotropic regulatory genes. Signal transduction is the process by which signals are transmitted from the cell surface to the nucleus or other cellular structures. It plays a fundamental role in regulating a wide range of developmental and physiological processes, many of which are likely to be subject to buffering mechanisms. Here we infer that contrasting selection pressures act on six components of the Ras signal transduction pathway by comparing sequences obtained from 25 alleles of Drosophila melanogaster with one allele of the sibling species D. simulans. The three most upstream components of the cascade, Ras, Drk and polehole, experience strong purifying selection, as they show no fixed amino acid differences between the species and just a handful of rare replacement polymorphisms within D. melanogaster. This portion of the pathway is likely to act as a control point in signal transduction, because the more downstream components Dsor1, corkscrew and Ksr, each show several amino acid replacements between the species. Furthermore, Ksr is nearly monomorphic within D. melanogaster, and application of the HKA and McDonald and Kreitman tests indicate that this gene may have experienced a recent selective sweep, suggesting that modifiers of Ras kinase signalling are the most likely source of quantitative variation associated with this core regulatory pathway.

Animals↗
PubMed2002

Developmental evolution: getting robust about robustness.

In the context of development, a process is robust if it can proceed normally despite the enormous capacity for perturbation inherent in all biological systems. A new mode of theoretical modeling of genetic networks holds great promise for increasing our understanding of both the quantitative mechanisms of robustness and its evolutionary impact.

Animals↗
PubMed2002

A genetic attack on the defense complex.

An increasing number of "non-model" organisms are becoming accessible to genetic analysis in the field, as evolutionary biologists develop dense molecular genetic maps. Peichel et al.'s recent study(1) provides a microsatellite-based map for threespine stickleback fish (Gasterosteus aculeatus), and the first evidence for QTL affecting feeding morphology and defensive armor. This species has undergone rapid and parallel morphological and behavioral evolution, and there is now hope that some of the genes responsible for the divergence may soon be identified.

Animals↗
PubMed2002

The evolution of developmental regulatory pathways.

Evolutionary analysis of the content of developmental regulatory pathways has been advanced by the publication of pairs of complete genome sequences from representative taxonomic groups. Annotation of the fission yeast, rice, and mouse genomes confirms that most regulatory families are shared among eukaryotes but also shows that certain gene families have restricted distributions. Theoretical advances in the past few years include development of the theory of scale-free networks, which provides a new framework in which to consider the connectivity and evolution of regulatory systems, and introduction of algorithms that use comparative data to enhance detection of transcriptional regulatory motifs.

Animals↗
PubMed2002

Enabling population and quantitative genomics.

Dissection of quantitative traits to the nucleotide level requires phenotypic and genotypic analysis of traits on a genome scale. Here we discuss the set of community-wide genetic and molecular resources, including panels of specific types of inbred lines and high density resequencing and SNP detection, that will facilitate such studies.

Animals↗
PubMed2002

Unusual genetic architecture of natural variation affecting drug resistance in Drosophila melanogaster.

Naturally occurring genetic variation was quantified for survival time of adult Drosophila melanogaster exposed to chronic ingestion of the drugs nicotine, caffeine, dopamine, tyramine and octopamine. Responses to nicotine, tyramine and octopamine were genetically correlated in both sexes, whereas caffeine response correlated with starvation resistance. However, there is also genetic variation that is specific for each of the drugs. Females tended to be more resistant than males to nicotine and caffeine but sex-by-genotype interactions were also seen for these drugs and for the response to dopamine. An unusual and complex genetic architecture was observed in crosses between lines with different responses to caffeine ingestion. Additive and dominance components were clearly seen from the analysis of F1 individuals, but increased female resistance to caffeine in backcross generations and increased male sensitivity in F2 generations confused the interpretation of possible epistatic contributions.

Analysis of Variance↗
PubMed2002

Microarrays in ecology and evolution: a preview.

Microarray technology provides a new tool with which molecular ecologists and evolutionary biologists can survey genome-wide patterns of gene expression within and among species. New analytical approaches based on analysis of variance will allow quantification of the contributions of among individual variation, genotype, sex, microenvironment, population structure, and geography to variation in gene expression. Applications of this methodology are reviewed in relation to studies of mechanisms of adaptation and divergence; delineation of developmental and physiological pathways and networks; characterization of quantitative genetic parameters at the level of transcription ('quantitative genomics'); molecular dissection of parasitism and symbiosis; and studies of the diversification of gene content. Establishment of microarray resources is neither prohibitively expensive nor technologically demanding, and a commitment to development of gene expression profiling methods for nonmodel organisms could have a tremendous impact on molecular and genetic research at the interface of organismal and population biology.

Animals↗